Clinical Studies

Abstracts are presented below for clinical studies on Gotu Kola.

  • Botanical Name: Centella Asiatica

  • Ayurvedic Name: Brahmi

  • Common Name: Gotu Kola

Centella Asiatica

Plant Phytonutrient Profile


1: J Ethnopharmacol. 2006 Nov 6; [Epub ahead of print]

Wound-healing activity of St. John's Wort (Hypericum perforatum L.) on chicken
embryonic fibroblasts.

Ozturk N, Korkmaz S, Ozturk Y.

Anadolu University, Faculty of Pharmacy, Department of Pharmacognosy, Tepebasi,
26470 Eskisehir, Turkey.

Wound-healing effect of St. John's Wort (Hypericum perforatum L.) extract was
evaluated by comparing with dexpanthenol and titrated extract of Centella
asiatica (TECA) on cultured chicken embryonic fibroblasts. Chicken embryonic
fibroblasts from fertilized eggs were incubated with the plant extract,
dexpanthenol and TECA. Using microscopical methods by staining cells, mitotic
ability, morphologic changes and collagen production in the cultured fibroblasts
were evaluated as parameters to approach its mechanism of action in wound
repair. Findings obtained in the present study indicated that Hypericum
perforatum extract exhibited a wound-healing activity whose mechanism of action
is similar to that of TECA. Wound-healing activity of Hypericum perforatum
extract seems to be mainly due to the increase in the stimulation of fibroblast
collagen production and the activation of fibroblast cells in polygonal shape,
which plays a role in wound repair by closing damaged area. The findings
demonstrated the wound-healing activity of Hypericum perforatum, which has
previously been based on ethnomedical data.

PMID: 17156955 [PubMed - as supplied by publisher]

2: Ceska Slov Farm. 2006 Sep;55(5):219-29.

[Plant metabolites as nootropics and cognitives]

[Article in Czech]

Cervenka F, Jahodar L.

Univerzita Karlova v Praze, Farmaceuticka fakulta v Hradci Kralove, Katedra
farmaceuticke botaniky a ekologie. [email protected]

Nowadays several millions of people suffer from Alzheimer's disease and other
types of dementia. Etiology of these diseases is not known very well. There
occur different levels of neurotransmitters, the level of acetylcholine in the
brain is decreased and pathological changes affect the brain tissue. Organic and
toxic damage of the brain, free radicals, and other changes participate in the
development of these diseases. Drugs as nootropics, cognitives, and
neuroprotectives are commonly used to treat these diseases. Some of these drugs
have often side and undesirable effects. In recent years some natural substances
(galanthamine, huperzine A, vinpocetine), and standardized plant extracts
(Ginkgo biloba L., Centella asiatica L.) Urban, Bacopa monniera L., Evolvulus
alsinoides L.) are often used. These plant preparations produce fewer
undesirable effects and the same effectiveness as the classic therapy, or these
preparations are used as a supplement to the classic therapy.

Publication Types:
English Abstract
Research Support, Non-U.S. Gov't
Review

PMID: 17128592 [PubMed - indexed for MEDLINE]

3: Ir Med J. 2006 Jul-Aug;99(7):219; author reply 219-20.

Comment on:
Ir Med J. 2005 Nov-Dec;98(10):250-1.

Night eating syndrome (NES).

Tan JW.

Publication Types:
Comment
Letter

PMID: 16989019 [PubMed - indexed for MEDLINE]

4: Evid Based Complement Alternat Med. 2006 Sep;3(3):349-57.

Centella asiatica (L.) Leaf Extract Treatment During the Growth Spurt Period
Enhances Hippocampal CA3 Neuronal Dendritic Arborization in Rats.

Mohandas Rao KG, Muddanna Rao S, Gurumadhva Rao S.

Centella asiatica (CeA) is a creeping plant growing in damp places in India and
other Asian countries. The leaves of CeA are used for memory enhancement in the
Ayurvedic system of medicine, an alternative system of medicine in India. In
this study, we have investigated the effect during the rat growth spurt period
of CeA fresh leaf extract treatment on the dendritic morphology of hippocampal
CA3 neurons, one of the regions of the brain concerned with learning and memory.
Neonatal rat pups (7 days old) were fed with 2, 4 or 6 ml kg(-1) body weight of
fresh leaf extract of CeA for 2, 4 or 6 weeks. After the treatment period the
rats were killed, their brains were removed and the hippocampal neurons were
impregnated with silver nitrate (Golgi staining). Hippocampal CA3 neurons were
traced using a camera lucida, and dendritic branching points (a measure of
dendritic arborization) and intersections (a measure of dendritic length) were
quantified. These data were compared with data for age-matched control rats. The
results showed a significant increase in the dendritic length (intersections)
and dendritic branching points along the length of both apical and basal
dendrites in rats treated with 4 and 6 ml kg(-1) body weight per day of CeA for
longer periods of time (i.e. 4 and 6 weeks). We conclude that the
constituents/active principles present in CeA fresh leaf extract have a neuronal
dendritic growth stimulating property; hence, the extract can be used for
enhancing neuronal dendrites in stress and neurodegenerative and memory
disorders.

PMID: 16951719 [PubMed - in process]

5: Int J Low Extrem Wounds. 2006 Sep;5(3):169-80.

A review of the microcirculation in skin in patients with chronic venous
insufficiency: the problem and the evidence available for therapeutic options.

Wollina U, Abdel-Naser MB, Mani R.

Department of Dermatology, Hospital Dresden-Friedrichstadt, Academic Teaching
Hospital of the Technical University of Dresden, Germany. [email protected]

Impairment of the cutaneous microcirculation is a major predisposing factor in
inflammation and ulceration in patients with chronic venous insufficiency (CVI).
Increase of capillary filtration rate predisposes to the formation of edema.
Local lymphedema is a complication of CVI, often underdiagnosed. This review is
focused on CVI but excludes the complication of ulceration. Treatment of
microcirculatory dysfunction can be done by pharmacologic intervention or
compression therapy or using a combination of both. This review is focused on
drugs that have been evaluated by randomized prospective controlled trials. The
following compounds are discussed: horse chestnut seed extracts, flavonoids, red
vine leaves extracts, total triterpenic fraction of Centella asiatica (L),
prociadins, calcium dobesilate, and pentoxifylline. The microcirculatory effects
of compression therapy using bandages or stockings are also reviewed. The major
microcirculatory effects that have been shown are the reduction of capillary
filtration rate and improvements in levels of transcutaneous partial pressures
of oxygen and carbon dioxide (TcPO(2) and TcPCO(2)). Available data suggest that
a combination of pharmacologic and compression therapy may have some additive
effects.

Publication Types:
Review

PMID: 16928673 [PubMed - indexed for MEDLINE]

6: Int J Low Extrem Wounds. 2006 Sep;5(3):137-43.

Effect of Centella asiatica L (Umbelliferae) on normal and
dexamethasone-suppressed wound healing in Wistar Albino rats.

Shetty BS, Udupa SL, Udupa AL, Somayaji SN.

Department of Biochemistry, Melaka Manipal Medical College, India.
[email protected]

Centella asiatica is a reputed medicinal plant used in the treatment of various
skin diseases in the Indian system of medicine. The objective of the study
presented in this article was to evaluate the wound-healing potential of the
ethanolic extract of the plant in both normal and dexamethasone-suppressed wound
healing. The study was done on Wistar albino rats using incision, excision, and
dead space wounds models. The extract of C asiatica significantly increased the
wound breaking strength in incision wound model compared to controls (P < .001).
The extract-treated wounds were found to epithelize faster, and the rate of
wound contraction was significantly increased as compared to control wounds (P <
.001). Wet and dry granulation tissue weights, granulation tissue breaking
strength, and hydroxyproline content in a dead space wound model also increased
at statistically significant levels as shown. The extract of the leaves had the
effect of attenuating the known effects of dexamethasone healing in all wound
models (P < .001, P < .05). The results indicated that the leaf extract promotes
wound healing significantly and is able to overcome the wound-healing
suppressing action of dexamethasone in a rat model. These observations were
supported by histology findings.

PMID: 16928669 [PubMed - indexed for MEDLINE]

7: Trop Biomed. 2005 Dec;22(2):165-70.

In vitro screening of five local medicinal plants for antibacterial activity
using disc diffusion method.

Zaidan MR, Noor Rain A, Badrul AR, Adlin A, Norazah A, Zakiah I.

Bioassay Unit, Herbal Medicine Research Centre, Institute for Medical Research,
Kuala Lumpur.

Medicinal plants have many traditional claims including the treatment of
ailments of infectious origin. In the evaluation of traditional claims,
scientific research is important. The objective of the study was to determine
the presence of antibacterial activity in the crude extracts of some of the
commonly used medicinal plants in Malaysia, Andrographis paniculata, Vitex
negundo, Morinda citrifolia, Piper sarmentosum, and Centella asiatica. In this
preliminary investigation, the leaves were used and the crude extracts were
subjected to screening against five strains of bacteria species, Methicillin
Resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Klebsiella
pneumoniae, Pseudomonas aeruginosa and Escherichia coli, using standard protocol
of Disc Diffusion Method (DDM). The antibacterial activities were assessed by
the presence or absence of inhibition zones and MIC values. M. citrifolia, P.
sarmentosum and C. asiatica methanol extract and A. paniculata (water extract)
have potential antibacterial activities to both gram positive S. aureus and
Methicillin Resistant S. aureus (MRSA). None of the five plant extracts tested
showed antibacterial activities to gram negative E. coli and K. pneumoniae,
except for A. paniculata and P. sarmentosum which showed activity towards P.
aeruginosa. A. paniculata being the most potent at MIC of 2 g/disc. This finding
forms a basis for further studies on screening of local medicinal plant extracts
for antibacteria properties.

PMID: 16883283 [PubMed - in process]

8: Phytochemistry. 2006 Sep;67(18):2041-9. Epub 2006 Jul 28.

The effect of methyl jasmonate on triterpene and sterol metabolisms of Centella
asiatica, Ruscus aculeatus and Galphimia glauca cultured plants.

Mangas S, Bonfill M, Osuna L, Moyano E, Tortoriello J, Cusido RM, Pinol MT,
Palazon J.

Laboratorio de Fisiologia vegetal, Facultad de Farmacia, Universidad de
Barcelona, Avda. Diagonal 643, E-08028 Barcelona, Spain.

Considering that exogenously applied methyl jasmonate can enhance secondary
metabolite production in a variety of plant species and that 2,3-oxidosqualene
is a common precursor of triterpenes and sterols in plants, we have studied
Centella asiatica and Galphimia glauca (both synthesizing triterpenoid secondary
compounds) and Ruscus aculeatus (which synthesizes steroidal secondary
compounds) for their growth rate and content of free sterols and respective
secondary compounds, after culturing with or without 100 microM methyl
jasmonate. Our results show that elicited plantlets of G. glauca and to a higher
degree C. asiatica (up to 152-times more) increased their content of
triterpenoids directly synthesized from 2,3-oxidosqualene (ursane saponins and
nor-seco-friedelane galphimines, respectively) at the same time as growth
decreased. In contrast, the free sterol content of C. asiatica decreased
notably, and remained practically unaltered in G. glauca. However, in the case
of R. aculeatus, which synthesizes steroidal saponins (mainly spirostane type)
indirectly from 2,3-oxidosqualene after the latter is converted to the plant
phytosterol-precursor cycloartenol, while the growth rate and free sterol
content clearly decreased, the spirostane saponine content was virtually
unchanged (aerial part) or somewhat lower (roots) in presence of the same
elicitor concentration. Our results suggest that while methyl jasmonate may be
used as an inducer of enzymes involved in the triterpenoid synthesis downstream
from 2,3-oxidosqualene in both C. asiatica and G. glauca plantlets, in those of
C. asiatica and R. aculeatus it inhibited the enzymes involved in sterol
synthesis downstream from cycloartenol.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16876832 [PubMed - indexed for MEDLINE]

9: J Med Assoc Thai. 2005 Nov;88 Suppl 3:S131-40.

Isobolographically additive anticonvulsant activity between Centella asiatica's
ethyl acetate fraction and some antiepileptic drugs.

Vattanajun A, Watanabe H, Tantisira MH, Tantisira B.

PhD Program of Inter-department of Physiology, Graduate School, Chulalongkorn
University, Bangkok, Thailand.

OBJECTIVE: To investigate interaction between orally given Centella asiatica's
ethyl acetate fraction (EACA) and intraperitoneally administered antiepileptic
drugs (AEDs), namely, phenytoin, valproate and gabapentin. MATERIAL AND METHOD:
Isobolographic analysis was used to evaluate the interaction between EACA and
AEDs in terms of protection of mice in the pentylenetetrazole test. Rotarod test
was used to evaluate neurotoxicity. RESULTS: When given alone, the median
effective dose of phenytoin, valproate and gabapentin were found to be 13, 104,
and 310 mg/kg BW, respectively, whereas the corresponding values in the presence
of EACA were 5, 29 and 79 mg/kg BW. Together with isobolographic analysis, the
results obtained indicated an additive effect among all combinations tested. In
relation to neurotoxicity, combination of gabapentin and EACA demonstrated a
broader margin between the effective dose and the neurotoxic dose while the
other two combinations did not. CONCLUSION: The present finding suggested a
potential of Centella asiatica to be developed as an adjunctive medication for
epileptic patients.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16858951 [PubMed - indexed for MEDLINE]

10: Mol Cell Biochem. 2007 Jan;294(1-2):55-63. Epub 2006 Jun 20.

Adriamycin induced myocardial failure in rats: Protective role of Centella
asiatica.

Gnanapragasam A, Yogeeta S, Subhashini R, Ebenezar KK, Sathish V, Devaki T.

Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600
025, Tamilnadu, India, [email protected]

Generation of reactive oxygen species and mitochondrial dysfunction has been
implicated in adriamycin induced cardiotoxicity. Mitochondrial dysfunction is
characterized by the accumulation of oxidized lipids, proteins and DNA, leading
to disorganization of mitochondrial structure and systolic failure. The present
study was aimed to evaluate the efficacy of Centella asiatica on the
mitochondrial enzymes; mitochondrial antioxidant status in adriamycin induced
myocardial injury. Adriamycin (2.5 mg/kg body wt., i.p.) induced mitochondrial
damage in rats was assessed in terms of decreased activities (p< 0.05) of
cardiac marker enzymes (lactate dehydrogenase, creatine phosphokinase, amino
transferases), TCA cycle enzymes (isocitrate dehydrogenase, alpha-ketoglutarate
dehydrogenase, malate dehydrogenase, respiratory marker enzymes
(NADH-dehydrogenase, cytochrome-C-oxidase), mitochondrial antioxidant enzymes
(GPx, GSH, SOD,CAT) and increased (p< 0.05) level of lipid peroxidation.
Mitochondrial damage was confirmed by transmission electron microscopic
examination. Pre-co-treatment with aqueous extract of Centella asiatica (200
mg/kg body wt, oral) effectively counteracted the alterations in mitochondrial
enzymes and mitochondrial defense system. In addition, transmission electron
microscopy study confirms the restoration of cellular normalcy and accredits the
cytoprotective role of Centella asiatica against adriamycin induced myocardial
injury. Our results demonstrated elevated oxidative stress and mitochondrial
dysfunction in adriamycin treated rats. Moreover, on the basis of our findings
it may be concluded that the aqueous extract of C. asiatica not only possesses
antioxidant properties but it may also reduce the extent of mitochondrial
damage.

PMID: 16786185 [PubMed - in process]

11: Phytochemistry. 2006 Jun;67(11):1143-50. Epub 2006 May 2.

Immunosuppressive diacetylenes, ceramides and cerebrosides from Hydrocotyle
leucocephala.

Ramos F, Takaishi Y, Kawazoe K, Osorio C, Duque C, Acuna R, Fujimoto Y, Sato M,
Okamoto M, Oshikawa T, Ahmed SU.

Pharmacognosy Laboratory, Graduate School of Pharmaceutical Sciences, University
of Tokushima, Shomashi 1-78, Tokushima 770-8505, Japan.

Three C-17 diacetylenic compounds (1-3), one monoterpenoid (4), seven ceramides
(leucoceramides A-G, 5a-g), six cerebrosides (leucocerebrosides A-F, 6a-f) and
nine known compounds were isolated from the methanolic extract of Hydrocotyle
leucocephala. Their structures were established by spectroscopic methods. The
isolated compounds 1-3, 5a-g, 6a-f and 7 were shown to be active in the
lipopolysaccharide (LPS) induced cytokine production assay for IL-10, IL-12, and
TNF-alpha.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16631830 [PubMed - indexed for MEDLINE]

12: J Pharm Pharmacol. 2006 Apr;58(4):547-59.

Changes in brain biogenic amines and haem biosynthesis and their response to
combined administration of succimers and Centella asiatica in lead poisoned
rats.

Saxena G, Flora SJ.

Division of Pharmacology and Toxicology, Defence Research and Development
Establishment, Jhansi Road, Gwalior-474 002, India.

This study was designed to investigate the therapeutic potential of meso
2,3-dimercaptosuccinic acid (DMSA) and one of its monoesters, monoisoamyl DMSA
(MiADMSA), individually or when administered in combination with an extract of
Centella asiatica against experimental lead intoxication in rats. Biochemical
variables indicative of alterations in the central nervous system and haem
biosynthesis were investigated to determine the toxicity in male Wistar rats.
Thirty five rats were exposed to 0.2% lead acetate for 10 weeks, followed by 10
days of treatment with DMSA and MiADMSA (50 mg kg(-1), i.p., once daily) alone
and in combination with C. asiatica (200 mg kg(-1), p.o., once daily).
Biochemical variables indicative of oxidative stress and brain biogenic amines,
along with lead concentration in blood and brain, were measured. Lead exposure
caused a significant depletion of blood and brain delta-aminolevulinic acid
dehydratase (ALAD) activity, an important enzyme of the haem biosynthesis
pathway, and glutathione (GSH) level. These changes were accompanied by a marked
increase in reactive oxygen species (ROS) level, thiobarbituric acid reactive
substances (TBARS), delta-aminolevulinic acid synthase (ALAS) and oxidized
glutathione (GSSG) activity in blood and brain. Significant depletion of brain
noradrenaline (norepinephrine, NE), 5-hydroxytryptamine (5-HT), dopamine (DA)
and acetylcholinesterase (AChE) also were observed following lead exposure. Also
seen was a significant depletion in brain glutathione peroxidase (GPx),
glutathione S-transferase (GST) and monoamine oxidase activity, as well as blood
and brain superoxide dismutase (SOD) activity. These biochemical changes were
correlated with an increased uptake of lead in blood and brain. Combined
administration of MiADMSA and C. asiatica was most effective in reducing these
alterations, including biogenic amines, besides reducing body lead burden,
compared with individual treatment with MiADMSA. Certain other biochemical
variables responded favourably to combination therapy and monotherapy with
MiADMSA. Thus, supplementation of C. asiatica during chelation could be
recommended for achieving optimum effects of chelation therapy.

Publication Types:
Comparative Study

PMID: 16597373 [PubMed - indexed for MEDLINE]

13: Planta Med. 2006 Mar;72(4):324-8.

Asiaticoside induces human collagen I synthesis through TGFbeta receptor I
kinase (TbetaRI kinase)-independent Smad signaling.

Lee J, Jung E, Kim Y, Park J, Park J, Hong S, Kim J, Hyun C, Kim YS, Park D.

Biospectrum Life Science Institute, Gunpo City, Gyunggi Do, Korea.

Skin aging appears to be principally related to a decrease in the levels of type
I collagen, the primary component of the skin dermis. Asiaticoside, a saponin
component isolated from Centella asiatica, has been shown to induce type I
collagen synthesis in human dermal fibroblast cells. However, the mechanism
underlying asiaticoside-induced type I collagen synthesis, especially at a
molecular level, remains only partially understood. In this study, we have
attempted to characterize the action mechanism of asiaticoside in type I
collagen synthesis. Asiaticoside was determined to induce the phosphorylation of
both Smad 2 and Smad 3. In addition, we detected the asiaticoside-induced
binding of Smad 3 and Smad 4. In a consistent result, the nuclear translocation
of the Smad 3 and Smad 4 complex was induced via treatment with asiaticoside,
pointing to the involvement of asiaticoside in Smad signaling. In addition,
SB431542, an inhibitor of the TGFbeta receptor I (TbetaRI) kinase, which is
known to be an activator of the Smad pathway, was not found to inhibit both Smad
2 phosphorylation and Type 1 collagen synthesis induced by asiaticoside.
Therefore, our results show that asiaticoside can induce type I collagen
synthesis via the activation of the TbetaRI kinase-independent Smad pathway.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16557473 [PubMed - indexed for MEDLINE]

14: Phytomedicine. 2006 Nov;13(9-10):668-76. Epub 2006 Feb 20.

Evaluation of anxiolytic properties of Gotukola--(Centella asiatica) extracts
and asiaticoside in rat behavioral models.

Wijeweera P, Arnason JT, Koszycki D, Merali Z.

Ottawa-Carleton Institute of Biology, University of Ottawa Institute of Mental
Health Research, Royal Ottawa Hospital, Canada.

The ayurvedic medicinal plant Gotukola (Centella asiatica) was evaluated for its
anxiolytic properties. Specifically, this study assessed the effects of:
Gotukola plant materials of different genotypic origin; hexane, ethyl acetate
and methanol extracts of Gotukola; and asiaticoside, a triterpenic compound
isolated from Gotukola. Various paradigms were used to assess the anxiolytic
activity, including the elevated plus maze (EPM), open field, social
interaction, locomotor activity, punished drinking (Vogel) and novel cage tests.
The EPM test revealed that Gotukola, its methanol and ethyl acetate extracts as
well as the pure asiaticoside, imparted anxiolytic activity. Furthermore, the
asiaticoside did not affect locomotor activity, suggesting these compounds do
not have sedative effects in rodents.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16488124 [PubMed - indexed for MEDLINE]

15: Arch Intern Med. 2006 Feb 13;166(3):370-1; author reply 371.

Comment on:
Arch Intern Med. 2005 Feb 14;165(3):296-301.

Studies on natural products.

Betz J, Costello R.

Publication Types:
Comment
Letter

PMID: 16476883 [PubMed - indexed for MEDLINE]

16: Ir Med J. 2005 Nov-Dec;98(10):250-1.

Comment in:
Ir Med J. 2006 Jul-Aug;99(7):219; author reply 219-20.

Night eating syndrome and Gotu Kola.

O'Brien B.

Publication Types:
Case Reports
Letter

PMID: 16445150 [PubMed - indexed for MEDLINE]

17: Phytomedicine. 2006 Feb;13(3):205-8. Epub 2005 Aug 15.

Herbal remedies for anxiety - a systematic review of controlled clinical trials.

Ernst E.

Complementary Medicine Peninsula Medical School, Universities of Exeter
Plymouth, UK. [email protected]

Anxiety is a prominent indication for herbal medicine. This systematic review
was therefore aimed at summarising the evidence for or against the anxiolytic
efficacy of such treatments. Six databases were searched for all randomised
clinical trials testing herbal monopreparations in the alleviation of anxiety.
Seven such studies and one systematic review were located. Eight different
herbals were studied. The herbal medicines, which, according to these data are
associated with anxiolytic activity in humans, are Piper methysticum and Bacopa
monniera. Only for kava were independent replications available. It was
concluded that there is a lack of rigorous studies in this area and that only
kava has been shown beyond reasonable doubt to have anxiolytic effects in
humans.

Publication Types:
Review

PMID: 16428031 [PubMed - indexed for MEDLINE]

18: J Appl Toxicol. 2006 May-Jun;26(3):213-22.

Effect of Centella asiatica on arsenic induced oxidative stress and metal
distribution in rats.

Gupta R, Flora SJ.

Division of Pharmacology and Toxicology, Defence Research and Development
Establishment, Gwalior, India.

Concomitant oral supplementation of Centella asiatica (100, 200 or 300 mg
kg(-1), orally once daily) during arsenic exposure (20 ppm in drinking water for
4 weeks) was investigated in rats for its protective value. The animals exposed
to arsenic (III) showed a significant inhibition of delta-aminolevulinic acid
dehydratase (ALAD) activity, a marginal decrease in glutathione (GSH) and an
increase in zinc protoporphyrin (ZPP) level in blood. Hepatic and renal
glutathione (GSH) decreased, while oxidized glutathione (GSSG) and
thiobarbituric acid reactive substance (TBARS) levels increased significantly in
the liver, kidney and brain. The activities of brain superoxide dismutase (SOD)
and catalase decreased marginally on arsenic exposure. Concomitant
administration of Centella asiatica showed a significant protective action on
inhibited blood ALAD activity and restored the blood GSH level, whereas most of
the other blood biochemical parameters remained unchanged on Centella asiatica
supplementation. Interestingly, most of the hepatic biochemical variables
indicative of oxidative stress showed protection. There was, however, a
significant protection observed in the altered kidney GSSG level and hepatic and
brain TBARS. Only a marginal beneficial effect of Centella asiatica on blood and
liver arsenic concentration was noted, particularly at the highest dose studies
(300 mg kg(-1)). No effect of Centella asiatica on most of the altered renal
biochemical parameters was noted. The results thus lead to the conclusion that
simultaneous supplementation of Centella asiatica significantly protects against
arsenic-induced oxidative stress but does not influence the arsenic
concentration in these organs. It can thus be suggested that co-administration
of Centella asiatica protects animals from arsenic-induced oxidative stress but
exhibits no chelating property. Further studies are recommended for determining
the effect of co-administration of Centella asiatica during chelation therapy
with a thiol chelator. Copyright 2006 John Wiley & Sons, Ltd.

PMID: 16389662 [PubMed - indexed for MEDLINE]

19: Dakar Med. 2005;50(2):77-81.

[Healing activity of methanolic extract of the barks of Spathodea campanulata
Beauv (Bignoniaceae) in rat experimental burn model]

[Article in French]

Sy GY, Nongonierma RB, Ngewou PW, Mengata DE, Dieye AM, Cisse A, Faye B.

Laboratoire de Pharmacologie, Faculte de Medecine et Pharmacie, Universite
Cheikh Anta Diop, BP 5005, Dakar, Senegal. [email protected]

Spathodea campanulata Beauv. (Bignoniaceae) is widely distributed through Africa
and found in particular in Cameroon and Senegal. It is used in traditional
herbal medicine for the treatment of ulcers, filaria, gonorrhea, diarrhea and
fever. S. campanulata was also known in Cameroon traditional medicine to have a
healing activity in burn wounds. The aim of the present study was to assess the
burn healing effectiveness of the methanolic extract of the barks of S.
campanulata ointment (MEBSCO) in comparison to those of Centella asiatica and
Peru's balm in experimental burn model in rats. Experimental burn was made in
rat under chloral anaesthesia with electric iron (200 degrees C) on the right
and left side of the medianus line. Topical applications of MEBSCO (2%, 10% and
49%) dose-dependently decreased the score damage of the burn site. Treatment
with 10% and 49% of MEBSCO varied the score damage from 5 to 1 +/- 0.4 and 5 to
0.2 +/- 0.5 (p < 0.05, n = 5) respectively, at day 15 after experimental burn.
As well as C. asiatica (1%) and Peru's balm (1%) ointments, MEBSCO (10% and 49%)
induced a complete burn healing on the 19-20th post burn day. This study shows
for the first time, the burn healing effectiveness of MEBSCO in experimental
burn model. It also provides a rational use of the S. campanulata barks in
traditional medicine to promote burn healing.

Publication Types:
English Abstract

PMID: 16295762 [PubMed - indexed for MEDLINE]

20: Asian Pac J Cancer Prev. 2005 Jul-Sep;6(3):396-400.

Immunomodulatory activities of Centella asiatica and Rhinacanthus nasutus
extracts.

Punturee K, Wild CP, Kasinrerk W, Vinitketkumnuen U.

Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang
Mai 50200, Thailand.

Centella asiatica (CA) and Rhinacanthus nasutus (RN )have been used for
treatment of various illnesses, but the mechanisms of action remain largely
unknown. This study focused on the influence of CA and RN extracts on
cell-mediated and humoral immune responses. In human peripheral blood
mononuclear cells (PBMCs), CA (water extract) and RN (water and ethanol
extracts) significantly increased proliferation and the production of IL-2 and
TNF-alpha. In contrast, an ethanol extract of CA inhibited human PBMC
mitogenesis and the production of IL-2 and TNF-alpha. BALB/c mice treated with
CA extracts (100 mg/kg bw) showed higher responses to both primary and secondary
antibodies against BSA when compared with non-treated group. Only the secondary
antibody response was increased in RN extract-treated mice. The present study
revealed immunomodulating activity of CA and RN extracts with regard to both
non-specific cellular and humoral immune responses. The data available to date
suggest that they may have chemopreventive or anticancer potential.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16236006 [PubMed - indexed for MEDLINE]

21: Physiol Behav. 2005 Nov 15;86(4):449-57. Epub 2005 Oct 6.

Centella asiatica treatment during postnatal period enhances learning and memory
in mice.

Rao SB, Chetana M, Uma Devi P.

Department of Radiobiology, Kasturba Medical College, Manipal 576104, India.

Present investigation was planned to evaluate the nootropic effect of Centella
asiatica. Three months old male Swiss albino mice were injected orally with
graded doses (200, 500, 700, 1000 mg/kg body weight) of C. asiatica aqueous
extract for 15 days to select an effective dose for nootropic studies. Animals
were tested in radial arm maze to assess the learning and memory performance.
Based on these results, mice were treated orally with 200 mg/kg of C. asiatica
for 15 days from day 15 to day 30 post partum (p.p.) and the nootropic effect
was evaluated on the 31st day and 6 months p.p. The behavioral (open field,
dark/bright arena, hole board and radial arm maze tests), biochemical
(acetylcholine esterase activity) and histological studies (dendritic
arborization) were carried out. Performance of juvenile and young adult mice was
significantly improved in radial arm maze and hole board tests, but locomotor
activity did not show any change compared to control. Treatment resulted in
increased acetylcholine esterase activity in the hippocampus. Dendritic
arborization of hippocampal CA3 neurons was also increased in terms of
intersections and branching points, both at one month and 6 months. Results of
the present investigation show that treatment during postnatal developmental
stage with C. asiatica extract can influence the neuronal morphology and promote
the higher brain function of juvenile and young adult mice.

PMID: 16214185 [PubMed - indexed for MEDLINE]

22: Zhong Yao Cai. 2005 Jun;28(6):492-6.

[Effects of total triterpenes of Centella asiatica on the corticosterone levels
in serum and contents of monoamine in depression rat brain]

[Article in Chinese]

Chen Y, Han T, Rui Y, Yin M, Qin L, Zheng H.

Pharmacy School, Shanghai Jiao Tong University, Shanghai.

OBJECTIVE: To investigate the possible effect of antidepressant effect of total
triterpentes of Centella asiatica. METHODS: The corticosterone levels in serum
were measured by fluorescence spectroscopy. The contents of monoamine
neurotransmitters and their metabolites in rats cortex, hippocamopus and
thalamus were evaluated by using HPLC with electrochemical detector. RESULTS:
Significant reduction of the corticosterone level in serum and increase of the
contents of 5-HT, NE, DA and their metabolites 5-HIAA, MHPG in rat brain were
observed. CONCLUSION: The antidepressant effect of total triterpenes of Centella
asiatica may be involved in ameliorating the function of HPA axis and increasing
the contents of monoamine neurotransmitters.

Publication Types:
English Abstract
Research Support, Non-U.S. Gov't

PMID: 16209267 [PubMed - indexed for MEDLINE]

23: Biomed Chromatogr. 2006 Feb;20(2):151-3.

Identification of triterpenoid compounds of Centella asiatica by thin-layer
chromatography and mass spectrometry.

Bonfill M, Mangas S, Cusido RM, Osuna L, Pinol MT, Palazon J.

Laboratorio de Fisiologia vegetal, Facultad de Farmacia, Universidad de
Barcelona, Avda. Diagonal 643, E-08028 Barcelona, Spain. [email protected]

The identification of the four principal triterpenoid components of Centella
asiatica has been achieved by TLC on silica gel plates and mass spectrometry, as
a modification of the method described in the European Pharmacopoeia (5th edn).
A combination of ethyl acetate and methanol as the mobile phase was found to be
successful in separating these compounds from the rest of the main components of
the extract. The spots were detected with anisaldehyde solution. The separated
compounds were confirmed by MALDI -TOF mass spectrometry. Copyright (c) 2005
John Wiley & Sons, Ltd.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16206136 [PubMed - indexed for MEDLINE]

24: Phytother Res. 2005 Jul;19(7):605-11.

Modification of gamma ray induced changes in the mouse hepatocytes by Centella
asiatica extract: in vivo studies.

Sharma R, Sharma J.

Department of Zoology, University of Rajasthan, Jaipur 302004, India.
[email protected]

Ionizing radiation, besides causing direct damage also generates reactive oxygen
species that are capable of inducing damage to various organs. Pretreatment with
Centella asiatica 1 h prior to irradiation at a dose rate of 100 mg/kg body
weight was found to be effective against radiation induced damage in the liver.
The number of normal hepatocytes was higher in the Centella asiatica pretreated
group in comparison with the irradiated only group. The number of binucleated
cells and abnormal hepatocytes was less in comparison with the animals
irradiated without Centella asiatica pretreatment.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16161023 [PubMed - indexed for MEDLINE]

25: J Environ Biol. 2005 Jan;26(1):79-89.

Toxicity and accumulation of lead and chromium in Hydrocotyle umbellata.

Yongpisanphop J, Kruatrachue M, Pokethitiyook P.

Department of Biology, Faculty of Science, Mahidol University, Bangkok 10400,
Thailand.

The aquatic plant, Hydrocotyle umbellata, was studied for its toxicity and
accumulation of lead (Pb) and chromium (Cr) in a synthetic solution. Plants were
cultured in a modified Hoagland's nutrient solutions supplemented with 20, 40,
60, 80, and 100 mg Pb/l as lead nitrate [Pb(NO3)2] and 2, 4, 6, 8, and 10 mg
Cr/l as potassium dichromate (K2Cr2O7). They were separately harvested after 3,
6, 9, and 12 days. Plants exposed to Pb and Cr showed significant decreases in
the biomass productivity and total chlorophyll content when the exposure time
and metal concentration were increased. The accumulation of Pb and Cr in the
plants was significantly increased, but it was not linear with the exposure time
and metal concentration. Both metals were accumulated higher in the roots than
in the shoots. The bioconcentration factor of Pb was higher than that of Cr at
the same exposure time, indicating a higher accumulation potential of Pb than Cr
in H. umbellata. Toxicity symptoms of both metals showed a reduction in the
production of new plantlets, withering of petioles, and change in color of roots
from light green to dark brown. Pb caused leaf chlorosis, whereas Cr caused leaf
necrosis. The toxicity symptoms increased when the exposure time and metal
concentration were increased.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16114465 [PubMed - indexed for MEDLINE]

26: J Pharm Pharmacol. 2005 Sep;57(9):1221-9.

Centella asiatica accelerates nerve regeneration upon oral administration and
contains multiple active fractions increasing neurite elongation in-vitro.

Soumyanath A, Zhong YP, Gold SA, Yu X, Koop DR, Bourdette D, Gold BG.

Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson
Park Road, Portland OR 97239, USA.

Axonal regeneration is important for functional recovery following nerve damage.
Centella asiatica Urban herb, also known as Hydrocotyle asiatica L., has been
used in Ayurvedic medicine for centuries as a nerve tonic. Here, we show that
Centella asiatica ethanolic extract (100 microg mL-1) elicits a marked increase
in neurite outgrowth in human SH-SY5Y cells in the presence of nerve growth
factor (NGF). However, a water extract of Centella was ineffective at 100 microg
mL-1. Sub-fractions of Centella ethanolic extract, obtained through silica-gel
chromatography, were tested (100 microg mL-1) for neurite elongation in the
presence of NGF. Greatest activity was found with a non-polar fraction (GKF4).
Relatively polar fractions (GKF10 to GKF13) also showed activity, albeit less
than GKF4. Thus, Centella contains more than one active component. Asiatic acid
(AA), a triterpenoid compound found in Centella ethanolic extract and GKF4,
showed marked activity at 1 microM (microg mL-1). AA was not present in GKF10 to
GKF13, further indicating that other active components must be present. Neurite
elongation by AA was completely blocked by the extracellular-signal-regulated
kinase (ERK) pathway inhibitor PD 098059 (10 microM). Male Sprague-Dawley rats
given Centella ethanolic extract in their drinking water (300-330 mg kg-1 daily)
demonstrated more rapid functional recovery and increased axonal regeneration
(larger calibre axons and greater numbers of myelinated axons) compared with
controls, indicating that the axons grew at a faster rate. Taken together, our
findings indicate that components in Centella ethanolic extract may be useful
for accelerating repair of damaged neurons.

Publication Types:
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

PMID: 16105244 [PubMed - indexed for MEDLINE]

27: Int J Food Sci Nutr. 2005 Jun;56(4):287-91.

Phenolic contents and antioxidant activity of some food and medicinal plants.

Bajpai M, Pande A, Tewari SK, Prakash D.

Nutraceutical Chemistry, National Botanical Research Institute, Lucknow, India.

To identify promising sources of antioxidants, some food and medicinal plants
were studied for total phenolic contents and antioxidant activity. The leaves,
bark and fruits of Terminalia arjuna, Terminalia bellerica, Terminalia chebula
and Terminalia muelleri, the leaves and fruits of Phyllanthus emblica, and the
seeds of Syzygium cumini were found to have high total phenolic contents
(72.0-167.2 mg/g) and high antioxidant activity (69.6-90.6%). Leaves of
Eucalyptusglobulus were a rich source of rutin, Moringa oleifera for kaempferol,
aerial parts of Centella asiatica for quercetin, fruits of T. bellerica and T.
chebula for gallic acid, and bark of T. arjuna, leaves and fruits of T.
bellerica and bark, leaves and fruits of T. muelleri for ellagic acid.

PMID: 16096138 [PubMed - indexed for MEDLINE]

28: Cochrane Database Syst Rev. 2005 Jul 20;(3):CD003229.

Phlebotonics for venous insufficiency.

Martinez MJ, Bonfill X, Moreno RM, Vargas E, Capella D.

Hospital de la Santa Creu i Sant Pau, Iberoamerican Cochrane Center, Service of
Epidemiology, Sant Antoni M. Claret, 171, Barcelona, Spain, 08041.
[email protected]

BACKGROUND: Chronic venous insufficiency (CVI) is a common condition caused by
inadequate blood flow through the veins, usually in the lower limbs. It can
result in considerable discomfort with symptoms such as pain, itchiness and
tiredness in the legs. Sufferers may also experience swelling and ulcers.
Phlebotonics are a class of drugs that are often used to treat CVI. OBJECTIVES:
To assess the efficacy of oral or topical phlebotonics. SEARCH STRATEGY: We
searched the Cochrane Peripheral Vascular Diseases Group trials register (April
2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library
Issue 2, 2005), MEDLINE (January 1966 to April 2005), EMBASE (January 1980 to
April 2005) and reference lists of articles. We also contacted pharmaceutical
companies. SELECTION CRITERIA: Randomised, double blind, placebo-controlled
trials (RCTs) assessing the efficacy of rutosides, hidrosmine, diosmine, calcium
dobesilate, chromocarbe, centella asiatica, disodium flavodate, french maritime
pine bark extract, grape seed extract and aminaftone in CVI patients at any
stage of the disease. DATA COLLECTION AND ANALYSIS: Two reviewers independently
extracted data and assessed trial quality. The effects of treatment were
estimated by relative risk (RR) or by standardised mean differences (SMD) by
applying a random effects statistical model. Sensitivity analyses were also
performed. MAIN RESULTS: Fifty-nine RCTs of oral phlebotonics were included, but
only 44 trials involving 4413 participants contained quantifiable data for the
efficacy analysis: 23 of rutosides, ten of hidrosmine and diosmine, six of
calcium dobesilate, two of centella asiatica, one of french maritime pine bark
extract, one of aminaftone and one of grape seed extract. No studies evaluating
topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the
inclusion criteria.Outcomes included oedema, venous ulcers, trophic disorders,
subjective symptoms (pain, cramps, restless legs, itching, heaviness, swelling
and paraesthesias), global assessment measures and side effects. The results of
many variables were heterogeneous. Phlebotonics showed some global benefit (i.e.
oedema reduction) (relative risk 0.72, 95% confidence interval 0.65 to 0.81).
The benefit for the remaining CVI signs and symptoms must be evaluated by
phlebotonic group. There were no quantifiable data on quality of life. AUTHORS'
CONCLUSIONS: There is not enough evidence to globally support the efficacy of
phlebotonics for chronic venous insufficiency. There is a suggestion of some
efficacy of phlebotonics on oedema but this is of uncertain clinical relevance.
Due to the limitations of current evidence, there is a need for further
randomised, controlled clinical trials with greater attention paid to
methodological quality.

Publication Types:
Meta-Analysis
Review

PMID: 16034893 [PubMed - indexed for MEDLINE]

29: Exp Gerontol. 2005 Aug-Sep;40(8-9):707-15.

Emerging role of Centella asiatica in improving age-related neurological
antioxidant status.

Subathra M, Shila S, Devi MA, Panneerselvam C.

Department of Biochemistry, Dr AL Mudaliar PG Institute of Basic Medical
Sciences, University of Madras, Taramani Campus, Chennai 600 113, India.

Free radicals have been hypothesized to play an important role in ageing
process. There exists an imbalance between free radical production and
antioxidant defense mechanism, which may lead to cell death during ageing. Our
study was designed to determine whether extract of Centella asiatica, an
antioxidant, when administered orally (300 mg/kg body weight/day) for 60 days
would prevent age-related changes in antioxidant defense system, lipid
peroxidation (LPO) and protein carbonyl (PCO) content in rat brain regions such
as cortex, hypothalamus, striatum, cerebellum and hippocampus. Aged rats
elicited a significant decline in the antioxidant status and increased the LPO
and PCO as compared to control rats in all five regions studied. The increase in
LPO and PCO contents were (64%, 34%) in cortex, (86%, 30%) in cerebellum, (51%,
47%) in striatum, (77%, 27%) in hypothalamus and (58%, 45%) in hippocampus,
respectively, in aged rats as compared to young rats. Supplementation of C.
asiatica was effective in reducing brain regional LPO and PCO levels and in
increasing the antioxidant status. Thus, C. asiatica by acting as a potent
antioxidant exerted significant neuroprotective effect and proved efficacious in
protecting rat brain against age related oxidative damage.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16026958 [PubMed - indexed for MEDLINE]

30: J Int Acad Periodontol. 2005 Jul;7(3):70-9.

Adjunctive periodontal treatment with Centella asiatica and Punica granatum
extracts in supportive periodontal therapy.

Sastravaha G, Gassmann G, Sangtherapitikul P, Grimm WD.

Department of Oral Medicine and Periodontics, Faculty of Dentistry, Mahidol
University, Bangkok, Thailand. [email protected]

BACKGROUND: Centella asiatica and Punica granatum are medicinal plants that have
been reported to promote tissue healing and modulate host responses. Preliminary
study revealed positive clinical effects of an innovative preparation from the
two herbal extracts in the form of biodegradable chips as a subgingival adjunct
to scaling and root planing. The purpose of this research was to evaluate
further augmenting efficacy the combined herbal preparation may have among
maintenance patients in comparison to standard supportive periodontal therapy
(SPT), with additional monitoring of certain inflammatory markers. METHODS:
Fifteen patients in the recall programme who had completed conventional
periodontal therapy with remaining probing pocket depths of 5-8 mm were
enrolled. After baseline examination and collection of gingival crevicular fluid
(GCF) samples, SPT was provided and the target teeth in the test group received
subgingival delivery of the medicated chips. The clinical parameters, which
included probing pocket depth (PD), attachment level (AL), bleeding index (BI),
gingival index (GI) and plaque index (PI) were recorded and GCF samples were
collected at baseline, 3 and 6 months. RESULTS: The results showed significant
improvement of PD, AL, and GI at 3 and 6 months and of BI at 6 months in the
test group as compared to control. No significant differences in PI were found
between the two treatment modalities at all subsequent visits. The test group
also showed statistically greater reduction of IL-1beta at both 3 and 6 months
and lower IL-6 concentration, which almost reached the level of significance at
6 months. CONCLUSION: The results indicate that adjunctive local delivery of
extracts from C. asiatica in combination with P. granatum significantly improved
clinical signs of chronic periodontitis and IL-1beta level in maintenance
patients.

Publication Types:
Clinical Trial
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

PMID: 16022023 [PubMed - indexed for MEDLINE]

31: Rev Enferm. 2005 May;28(5):67-70.

[Topical chemotherapy for the treatment of burns]

[Article in Spanish]

Salas Campos L, Fernandes Mansilla M, Martinez de la Chica AM.

D.U.E. Hospital General Vall d'Hebron.

A burn is a tissue lesion which provokes different alterations that vary from
topical erythema to total destruction of the structures affected. A burn always
produces an alteration in the skin, a lesion in the corneal strata is sufficient
to cause the skin to lose its capacity to act as a barrier. The objective the
treatment for a burn has is to produce epithelization as soon as possible in
order to prevent infection and to reduce functional and esthetic aftereffects.
Infection is the main cause of death due to burns due to the growth of
endogenous flora or due to external contamination. The use of topical
chemotherapy is fundamental to prevent infections when there are deep and
superficial burns or extensive intermediary burns. Centella asiatica extract has
proven to be efficient in helping, maintaining and regularizing cicatrisation of
skin affected by burns. Its usage combined with an antibiotic agent such as
neomycin covers the bacterial spectrum for gram-positive or -negative
microorganisms, guaranteeing an anti-infectious efficiency for this extract.

Publication Types:
English Abstract

PMID: 15981974 [PubMed - indexed for MEDLINE]

32: Arch Pharm Res. 2005 Apr;28(4):502-8.

Advanced formulation and pharmacological activity of hydrogel of the titrated
extract of C. asiatica.

Hong SS, Kim JH, Li H, Shim CK.

Department of Pharmaceutics, College of Pharmacy, Seoul National University,
Seoul 151-742, Korea.

Titrated extract of Centella asiatica (TECA) contains three principal
ingredients, asiaticoside (AS), asiatic acid (AA), and madecassic acid (MA).
These components are known to be clinically effective on systemic scleroderma,
abnormal scar formation, and keloids. However, one problem associated with
administration of TECA is its low solubility in aqueous as well as oil medium.
In this study, various nonionic surfactants and bile salts as anionic surfactant
were tested and screened for solubilizing TECA with a view to developing topical
hydrogel type of ointment which is stable physicochemically, and has better
pharmacological effects. When TECA was incorporated into various nonionic
surfactant systems, labrasol had the most potent capacity for solubilizing TECA.
In cases of bile salt systems, Na-deoxycholate (Na-DOC) had foremost
solubilizing capacity, even more than labrasol. In differential scanning
calorimetric study, the peaks of AA, MA, AS and Na-DOC disappeared at the
coprecipitate of 1% TECA and 1% Na-DOC, suggesting the optimum condition of
Na-DOC for solubilizing TECA. When the physicochemical stability of hydrogel
containing this mixture was assessed, it was stable at room temperature for at
least one month. Pharmacologically it significantly decreased the size of wound
area at the 9th day when applied to the wound area of rat dorsal skin. Taken
together, solubility of TECA was dramatically improved by using nonionic and
anionic surfactant systems, and Na-DOC was found to be the most effective
solubilizer of TECA in formulating a TECA-containing hydrogel typed ointment.
Moreover this gel was considered to be applicable to clinical use for wound
healing effect.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15918527 [PubMed - indexed for MEDLINE]

33: Mol Cells. 2005 Apr 30;19(2):294-9.

Cloning and expression of a farnesyl diphosphate synthase in Centella asiatica
(L.) Urban.

Kim OT, Ahn JC, Hwang SJ, Hwang B.

Department of Biology and Institute of Plant Resources, Chonnam National
University, Gwangju 500-757, Korea.

A cDNA encoding farnesyl diphosphate synthase (FPS; EC2.5.1.1/EC2.5.1.10) was
isolated from Centella asiacita (L.) Urban, using degenerate primers based on
two highly conserved domains. A full-length cDNA clone was subsequently isolated
by rapid amplification of cDNA ends (RACE) PCR. The sequence of the CaFPS (C.
asiatica farnesyl diphosphate synthase) cDNA contains an open reading frame of
1029 nucleotides encoding 343 amino acids with a molecular mass of 39.6 kDa. The
deduced CaFPS amino acid sequence exhibits 84, 79, and 72%, identity to the FPSs
of Artemisia annua, Arabidopsis thaliana, and Oryza sativa, respectively.
Southern blot analysis suggested that the C. asiatica genome contains only one
FPS gene. An artificially expressed soluble form of the CaFPS was identified by
SDS-PAGE. It had high specific activity and produced farnesyl diphosphate as the
major isoprenoid.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 15879717 [PubMed - indexed for MEDLINE]

34: Int J Low Extrem Wounds. 2003 Mar;2(1):25-39.

Plant medicines of Indian origin for wound healing activity: a review.

Biswas TK, Mukherjee B.

Department of Sharira Kriya, J. B. Roy State Ayurvedic Medical College and
Hospital.

Research on wound healing drugs is a developing area in modern biomedical
sciences. Scientists who are trying to develop newer drugs from natural
resources are looking toward the Ayurveda, the Indian traditional system of
medicine. Several drugs of plant, mineral, and animal origin are described in
the Ayurveda for their wound healing properties under the term Vranaropaka. Most
of these drugs are derived from plant origin. Some of these plants have been
screened scientifically for the evaluation of their wound healing activity in
different pharmacological models and patients, but the potential of most remains
unexplored. In a few cases, active chemical constituents were identified. Some
Ayurvedic medicinal plants, namely, Ficus bengalensis, Cynodon dactylon,
Symplocos racemosa, Rubia cordifolia, Pterocarpus santalinus, Ficus racemosa,
Glycyrrhiza glabra, Berberis aristata, Curcuma longa, Centella asiatica,
Euphorbia nerifolia, and Aloe vera, were found to be effective in experimental
models. This paper presents a limited review of plants used in Ayurvedic
medicine.

PMID: 15866825 [PubMed]

35: Plant Cell Rep. 2005 Jul;24(5):304-11. Epub 2005 Apr 15.

Cloning of a cDNA probably encoding oxidosqualene cyclase associated with
asiaticoside biosynthesis from Centella asiatica (L.) Urban.

Kim OT, Kim MY, Huh SM, Bai DG, Ahn JC, Hwang B.

Department of Biology, Chonnam National University, Gwangju, 500-757, South
Korea.

A homology-based PCR method was used to clone a cDNA encoding oxidosqualene
cyclase from Centella asiatica, which produces a large quantity of triterpene
saponins such as asiaticoside and madecassoside. Sequence analysis of one clone
found sequences related to beta-amyrin synthase. An open reading frame in the
full-length clone was named CabAS (Centella asiatica putative beta-amyrin
synthase). On the basis of amino acid sequence, CabAS appears to be an enzyme
(beta-amyrin synthase) that synthesizes beta-amyrin. Southern analysis showed
that the C. asiatica genome contains one copy of the CabAS gene. Northern blot
analysis demonstrated that the CabAS gene is expressed in leaves with no
detectable transcript in other plant tissues, consistent with the organ-specific
accumulation of the asiaticoside. Up-regulation of expression of CabAS by methyl
jasmonate in leaves was also demonstrated.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15834571 [PubMed - indexed for MEDLINE]

36: Rev Esp Enferm Dig. 2005 Feb;97(2):115-24.

Hepatotoxicity associated with the ingestion of Centella asiatica.

[Article in English, Spanish]

Jorge OA, Jorge AD.

Gastroenterology Department, Hospital Espanol, Mendoza, Argentina.
[email protected]

BACKGROUND: Hepatotoxicity due to herbal remedies is being increasingly
recognized. Centella asiatica (Centella asiatica Linn Urban) is commercialized
for multiple conditions. Its active principles are pentacyclic triterpenic
saponosides (asiaticoside, madecassoside). CLINICAL CASE STUDIES: We present
three women (61, 52 and 49 years old) who developed jaundice after taking
Centella asiatica for 30, 20 and 60 days. Respective laboratory tests: ALT:
1193, 1694 and 324 U/L; ALP: 503, 472 and 484 U/L; bilirubin: 4.23, 19.89 and
3.9 mg/dl. The first patient also had ASMA 1/160 and AMA 1/320. Respective
pathological diagnoses: granulomatous hepatitis with marked necrosis and
apoptosis; chronic hepatitis with cirrhotic transformation and intense
necroinflammatory activity, and granulomatous hepatitis. All patients improved
with Centella asiatica discontinuation, and ursodeoxycholic acid 10 mg/kg/day.
The first patient took Centella asiatica again, with recurrence of the damage.
The second one had taken this herb a year before. CONCLUSIONS: Many plants
synthesize hepatotoxic compounds. Germander, Skullcap and Glycyrrhizin contain
di- or triterpenic active principles, which can produce hepatic injury by
promoting apoptosis and altering cell membranes. We hypothesize that these
mechanisms may have resulted in injuries associated with Centella asiatica. The
presence of autoantibodies and granulomas also favors an immune-mediated
mechanism. Ursodeoxycholic acid has anti-apoptotic properties, but we cannot
rule out that Centella asiatica discontinuation alone may have resulted in
patient improvement.

Publication Types:
Case Reports

PMID: 15801887 [PubMed - indexed for MEDLINE]

37: Electrophoresis. 2005 Feb;26(3):648-60.

Precision improvement for the analysis of flavonoids in selected Thai plants by
capillary zone electrophoresis.

Suntornsuk L, Anurukvorakun O.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University,
Bangkok, Thailand. [email protected]

A capillary zone electrophoresis (CZE) method for the analyses of kaempferol in
Centella asiatica and Rosa hybrids and rutin in Chromolaena odorata was
developed. The optimization was performed on analyses of flavonoids (e.g.,
rutin, kaempferol, quercetin, myricetin, and apigenin) and organic carboxylic
acids (e.g., ethacrynic acid and xanthene-9-carboxylic acid) by investigation of
the effects of types and amounts of organic modifiers, background electrolyte
concentrations, temperature, and voltage. Baseline separation (R(s) = 2.83) of
the compounds was achieved within 10 min in 20 mM NaH2PO4 - Na2HPO4 (pH 8.0)
containing 10% v/v ACN and 6% v/v MeOH using a voltage of 25 kV, a temperature
of 30 degrees C, and a detection wavelength set at 220 nm. The application of
the corrected migration time (t(c)), using ethacrynic acid as the single marker,
was efficient to improve the precision of flavonoid identification (% relative
standard deviation (RSD) = 0.65%). The method linearity was excellent (r2 >
0.999) over 50-150 microg/mL. Precision (%RSD < 1.66%) and recoveries were good
(> 96% and %RSDs < 1.70%) with detection and quantitation limits of 2.23 and
7.14 microg/mL, respectively. Kaempferol in C. asiatica and R. hybrids was 0.014
g/100 g (%RSD = 0.59%) and 0.044 g/100 g (%RSD = 1.04%), respectively, and rutin
in C. odorata was 0.088 g/100 g (%RSD = 0.06%).

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15690438 [PubMed - indexed for MEDLINE]

38: Planta Med. 2004 Dec;70(12):1150-4.

Inhibitory effects of Centella asiatica water extract and asiaticoside on
inducible nitric oxide synthase during gastric ulcer healing in rats.

Guo JS, Cheng CL, Koo MW.

Department of Pharmacology, Faculty of Medicine, The University of Hong Kong,
Hong Kong.

In this study, the effects of Centella asiatica water extract (CE) and its
active constituent, asiaticoside (AC), on the expression and activity of
inducible nitric oxide synthase (iNOS) during gastric ulcer healing in rats were
investigated. CE was prepared from Centella asiatica dry plant and the
concentration of AC in CE was quantitatively determined with the use of high
performance liquid chromatography analysis. Different concentrations of CE (0.10
g/kg and 0.25 g/kg) and AC (5 mg/kg and 10 mg/kg) were orally administered to
rats with acetic acid-induced gastric ulcers. They were found to reduce the size
of the ulcers at days 1, 3 and 7 after ulcer induction in a dose-dependent
manner, with a concomitant attenuation of iNOS activity and protein expression
at the ulcer tissues. The levels of nitrite and nitrate (NO(X)-), the stable
end-products of nitric oxide (NO), in the gastric ulcer tissues were also
decreased. N-[3-(aminomethyl)benzyl]acetamidine (1400W), a highly selective
inhibitor of iNOS, was found to produce similar but more potent inhibition on
iNOS activity at a dose of 0.1 mg/kg. These findings indicate that CE and AC
have an anti-inflammatory property that is brought about by inhibition of NO
synthesis and thus facilitates ulcer healing.

PMID: 15643549 [PubMed - indexed for MEDLINE]

39: Cancer Lett. 2005 Jan 31;218(1):81-90.

Asiatic acid induces apoptosis in SK-MEL-2 human melanoma cells.

Park BC, Bosire KO, Lee ES, Lee YS, Kim JA.

College of Pharmacy, Yeungnam University, Gyongsan 712-749, South Korea.

Asiatic acid (AA) is a pentacyclic triterpene found in Centella asiatica. In the
present study, the mechanism of anticancer effect of AA on skin cancer was
investigated. AA decreased viability and induced apoptosis in human melanoma
SK-MEL-2 cells in a time- and dose-dependent manner. AA also markedly increased
intracellular reactive oxygen species (ROS) level and enhanced the expression of
Bax but not Bcl-2 protein in the cells. In addition, AA-induced activation of
caspase-3 activity in a dose-dependent manner. Pretreatment with Trolox, an
antioxidant, significantly blocked the induction of Bax and activation of
caspase-3 in AA-treated cells. Furthermore, Ac-DEVD-CHO, a specific caspase-3
inhibitor, and Trolox prevented the AA-induced apoptosis. AA did not elevate p53
nuclear protein levels that are present in a mutant form in SK-MEL-2 cells.
These results suggest that AA-induced apoptosis may be mediated through
generation of ROS, alteration of Bax/Bcl-2 ratio and activation of caspase-3,
but p53-independent. These results further suggest that AA may be a good
candidate for the therapeutic intervention of human skin cancer.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15639343 [PubMed - indexed for MEDLINE]

40: Biol Pharm Bull. 2005 Jan;28(1):173-5.

Antiproliferative constituents from Umbelliferae plants VII. Active triterpenes
and rosmarinic acid from Centella asiatica.

Yoshida M, Fuchigami M, Nagao T, Okabe H, Matsunaga K, Takata J, Karube Y,
Tsuchihashi R, Kinjo J, Mihashi K, Fujioka T.

Faculty of Pharmaceutical Sciences, Fukuoka University, Japan.

The antiproliferative constituents in the MeOH extract from the aerial parts of
Centella asiatica were investigated. Activity-guided fractionation of MeOH
extract resulted in the isolation of ursolic acid lactone, ursolic acid, pomolic
acid, 2alpha,3alpha-dihydroxyurs-12-en-28-oic acid, 3-epimaslinic acid, asiatic
acid, corosolic acid, and rosmarinic acid. Antiproliferative activity of the
isolated compounds against human gastric adenocarcinoma (MK-1), human uterine
carcinoma (HeLa), and murine melanoma (B16F10) cells was estimated.

PMID: 15635187 [PubMed - indexed for MEDLINE]

41: Ai Zheng. 2004 Dec;23(12):1599-604.

[Asiaticoside inducing apoptosis of tumor cells and enhancing anti-tumor
activity of vincristine.]

[Article in Chinese]

Huang YH, Zhang SH, Zhen RX, Xu XD, Zhen YS.

Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences and
Peking Union Medical College, Beijing 100050, P.R. China.

BACKGROUND & OBJECTIVE: Asiaticoside (ATS), a triterpene extracted from Centella
asiatica (L.) Urban, a traditional Chinese herb, possesses good wound healing
activities because of its stimulative effect on collagen synthesis. Recently,
the anti-tumor effect of asiaticiside has been reported. This study was to
examine the induction of apoptosis in cancer cells, and the enhancement of
vincristine (VCR) cytotoxicity by asiaticoside. METHODS: MTT assay was used to
evaluate inhibitory effect of asiaticoside combined with vincristine on
proliferation of several cancer cell lines, including KB, KBv200, MCF-7, and
MCF-7/ADM. Cell cycle, and apoptosis of KB cells were analyzed by flow
cytometry; apoptosis induction was also proved by electrophoresis,and
morphologic assessment; the expression of apoptosis-, and cell cycle-related
proteins were determined by Western blot. RESULTS: The IC(50) values of
asiaticoside for KB, KBv200, MCF-7, and MCF-7/ADM cells detected by MTT assay
were (1.11+/-0.13) mg/ml, (1.82+/-0.08) mg/ml, (1.58+/-0.15) mg/ml, and
(3.25+/-0.46) mg/ml, respectively. Multidrug resistant KBv200, and MCF-7/ADM
cancer cells displayed similar sensitivity to asiaticoside as their parental
counterparts (KB, and MCF-7 cells). Moreover, asiaticoside induced apoptosis in
KB cells. At sub-cytotoxicity concentration, asiaticoside showed synergistic
effect with vincristine in these 4 cell lines. The apoptosis rates were much
higher in asiaticoside plus vincristine groups than in vincristine or
asiaticoside groups. Bcl-2 phosphorylation levels were higher in the combination
groups than in vincristine or asiaticoside alone groups. The activated caspase-3
protein was only presented in the combination groups. Asiaticoside plus
vincristine enhanced S-G(2)/M arrest, up-regulated Cyclin B1 protein expression,
and down-regulated P34(cdc2) protein expression in KB cells. CONCLUSION:
Asiaticoside, as a biochemical modulator, may induce apoptosis,and enhance
anti-tumor activity of vincristine in cancer cells, might be useful in cancer
chemotherapy.

Publication Types:
English Abstract
Research Support, Non-U.S. Gov't

PMID: 15601545 [PubMed - indexed for MEDLINE]

42: Life Sci. 2004 Dec 17;76(5):585-97.

Protective effect of Centella asiatica on antioxidant tissue defense system
against adriamycin induced cardiomyopathy in rats.

Gnanapragasam A, Ebenezar KK, Sathish V, Govindaraju P, Devaki T.

Department of Biochemistry, University of Madras, Guindy Campus, Chennai- 600
025, Tamilnadu, India.

Increased oxidative stress and antioxidant deficit have been suggested to play a
major role in adriamycin induced cardiomyopathy and congestive heart failure due
to multiple treatments with adriamycin. In this study the cardio protective
effect of Centella asiatica on myocardial marker enzymes and antioxidant enzymes
in adriamycin induced cardiomyopathy was investigated in rats. The rats
administered with adriamycin (2.5 mg/kg body wt, i.p) caused myocardial damage
that was manifested by the elevation of serum marker (LDH, CPK, GOT and GPT)
enzymes and showed significant changes in the antioxidant enzymes (SOD, CAT,
GPx, GST). Pre-co-treatment with Centella asiatica(200 mg/kg of body wt/oral)
extract significantly prevented these alterations and restored the enzyme
activities to near normal levels. These findings demonstrate the cardio
protective effect of Centella asiatica on antioxidant tissue defense system
during adriamycin induced cardiac damage in rats.

PMID: 15556170 [PubMed - indexed for MEDLINE]

43: Int J Dermatol. 2004 Nov;43(11):801-7.

Asiaticoside induction for cell-cycle progression, proliferation and collagen
synthesis in human dermal fibroblasts.

Lu L, Ying K, Wei S, Fang Y, Liu Y, Lin H, Ma L, Mao Y.

From the State Key Laboratory of Genetic Engineering, Institute of Genetics,
School of Life Science, Fudan University, Shanghai, China. [email protected]

Asiaticoside, isolated from Centella asiatica, promotes fibroblast proliferation
and extracullar matrix synthesis in wound healing. The precise mechanism,
however, in molecular and gene expression levels still remains partially
understood. Using cDNA microarray technology, the alternation of genes
expression profiles was determined in a human dermal fibroblast in vitro in the
presence of asiaticoside (30 microg/ml). Fifty-four genes, with known functions
for cell proliferation, cell-cycle progression and synthesis of the
extracellular matrix, were significantly up-regulated in our "whole-genes nest"
expression profile at various timepoints. Furthermore, mRNA levels and protein
productions of certain genes responsible for extracellular matrix (ECM)
synthesis (e.g. encoding type I and type III collagen proteins) were evaluated
by Northern blot and radioimmunoassay, respectively. As a result, there is a
close correlation among the gene profile, mRNA and protein production in the
cells response to asiaticoside stimulation. This information could be used for
exploring the target genes in response to asiaticoside in fibroblasts.

PMID: 15533060 [PubMed - indexed for MEDLINE]

44: J Ethnopharmacol. 2004 Dec;95(2-3):183-9.

Thai medicinal plants modulate nitric oxide and tumor necrosis factor-alpha in
J774.2 mouse macrophages.

Punturee K, Wild CP, Vinitketkumneun U.

Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang
Mai 50200, Thailand.

Centella asiatica (CA) and Rhinacanthus nasutus (RN) are Thai medicinal plants
traditionally used to treat a variety of disorders including inflammatory
conditions and infections. Nitric oxide (NO) produced from activated macrophages
plays a role in both inflammatory and anti-inflammatory processes. This study
examined whether CA and RN modulate the production of NO and tumour necrosis
factor-alpha (TNF-alpha) by J774.2 mouse macrophages. Expression of the
inducible nitric oxide synthase (iNOS) and TNF-alpha genes was also analysed.
With CA (water extract) NO production was increased in a dose-dependent manner.
An increase also occurred when CA was administered with lipopolysaccharide
(LPS), a known macrophage activator. In contrast, an ethanol extract of CA had
no effect on NO, and when administered with LPS the extract suppressed
production. With RN, neither water nor ethanol extracts alone had an effect on
NO, although when the ethanol extract of RN was used in combination with LPS,
production was increased. TNF-alpha secretion was correlated with NO production
and increases were associated with an elevation in TNF-alpha mRNA. The only
effect on iNOS gene expression was an inhibition with the CA ethanol extract in
the presence of LPS, consistent with the reduction in NO under these conditions.
These studies show that CA and RN extracts can either increase or decrease NO
production by macrophages and that these effects are predominantly mediated
through an effect on TNF-alpha expression. These data contribute to a better
mechanistic understanding of the medicinal properties of these Thai plants.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15507334 [PubMed - indexed for MEDLINE]

45: Food Chem Toxicol. 2004 Dec;42(12):1987-97.

Inhibitory effects of Centella asiatica on azoxymethane-induced aberrant crypt
focus formation and carcinogenesis in the intestines of F344 rats.

Bunpo P, Kataoka K, Arimochi H, Nakayama H, Kuwahara T, Bando Y, Izumi K,
Vinitketkumnuen U, Ohnishi Y.

Department of Molecular Bacteriology, Graduate School of Medicine, The
University of Tokushima, Tokushima 770-8503, Japan.

Effects of the water extract of Centella asiatica Linn. on formation of
azoxymethane (AOM)-induced aberrant crypt foci (ACF) and intestinal
tumorigenesis in male F344 rats were investigated. Treatment with the extract
significantly decreased the number of larger ACF (with four or more crypts per
focus) in the large intestine in the early stage, while the number of methylated
DNA adducts was not decreased compared with that in the AOM-treated group. In
the post-initiation stage, the extract significantly decreased the total number
of ACF and the number of larger ACF, accompanied by a decrease in the
5-bromo-2'-deoxyuridine-labeling index and an increase in the induction of
apoptotic cells in the colonic mucosa. The incidences of neoplasms, the numbers
of adenocarcinomas in the small intestines and entire intestines, and sizes of
neoplasms in the entire intestines in rats fed C. asiatica extract at a dose of
10 mg/kg were smaller than those in rats given AOM alone (p < 0.05). The extract
at a dose of 100 mg/kg significantly reduced the multiplicity of neoplasms in
the small intestine (p < 0.05). These results suggest that inhibition of the
formation of AOM-induced ACF by C. asiatica extract is associated with
modification of cell proliferation and induction of apoptosis in colonic crypts
and that the extract has a chemopreventive effect on colon tumorigenesis.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15500935 [PubMed - indexed for MEDLINE]

46: Br J Dermatol. 2004 Sep;151(3):571-8.

Dermal fibroblast-associated gene induction by asiaticoside shown in vitro by
DNA microarray analysis.

Lu L, Ying K, Wei S, Liu Y, Lin H, Mao Y.

State Key Laboratory of Genetic Engineering, Institute of Genetics, School of
Life Science, Fudan University, Shanghai 200433, People's Republic of China.
[email protected]

BACKGROUND: Asiaticoside, isolated from Centella asiatica, promotes fibroblast
proliferation and extracellular matrix (ECM) synthesis in wound healing. The
precise mechanism, however, in molecular and gene expression levels is still
unclear. OBJECTIVE: Using cDNA microarray technology, the alteration of gene
expression profiles was determined for human dermal fibroblasts in vitro in the
presence of asiaticoside (30 microg mL(-1)). Fifty-four genes, with known
functions for cell proliferation, cell cycle progression and synthesis of ECM,
were significantly upregulated in our 'genome-nest' expression profile at
various time points. Furthermore, the mRNA levels and protein production of
certain genes responsible for ECM synthesis (e.g. encoding type I and type III
collagen proteins) were evaluated by Northern blot and radioimmunoassay,
respectively. RESULTS: We found that there is a close correlation between the
gene profile, mRNA and protein production in the response of the cells to
asiaticoside stimulation. CONCLUSIONS: This information could be used for
exploring the response of the target genes to asiaticoside in fibroblasts.

PMID: 15377342 [PubMed - indexed for MEDLINE]

47: Zhongguo Zhong Xi Yi Jie He Za Zhi. 2004 Aug;24(8):731-4.

[Effect of total glucosides of Centella asiatica on antagonizing liver fibrosis
induced by dimethylnitrosamine in rats]

[Article in Chinese]

Ming ZJ, Liu SZ, Cao L.

Department of Pharmacy, School of Medicine, Suzhou University, Jiangsu (215007).
[email protected]

OBJECTIVE: To investigate the anti-liver fibrosis effect of total glucosides of
Centella asiatica (GCA) in experimental rats. METHODS: Rat liver fibrosis model
was induced by injecting dimethylnitrosamine (DMN) intraperitoneally for 6
weeks. Rats were randomly divided into 6 groups, the normal group, the model
group, the positive control group treated by colchicine, and the three GCA
groups treated by high, moderate and low dosage of GCA through gastrogavage
started simultaneously with the modeling. At the end of the experiment, levels
of serum total protein (TP), albumin (ALB), alanine transaminase (ALT),
aspartate aminotransferase (AST), hyaluronic acid (HA), laminin (LN) were
measured, and the pathology of liver tissue was observed. RESULTS: The liver
function in the GCA groups was improved, the levels of serum ALT, AST, HA were
significantly lower than those in the model group (P < 0.05). Histopathological
observation showed that GCA has significant anti-liver fibrosis effect.
CONCLUSION: GCA has significant preventive and therapeutic effect on DMN induced
liver fibrosis in rats.

Publication Types:
English Abstract
Research Support, Non-U.S. Gov't

PMID: 15366600 [PubMed - indexed for MEDLINE]

48: Plant Cell Rep. 2004 Nov;23(5):339-44. Epub 2004 Aug 14.

Stimulation of asiaticoside accumulation in the whole plant cultures of Centella
asiatica (L.) urban by elicitors.

Kim OT, Kim MY, Hong MH, Ahn JC, Hwang B.

Department of Biology, Chonnam National University, Gwangju, 500-757, South
Korea.

The effects of a number of different elicitors on asiaticoside production in
whole plant cultures of Centella asiatica were studied, including yeast extract,
CdCl(2), CuCl(2) and methyl jasmonate (MJ). Only MJ and yeast extract stimulated
asiaticoside production--1.53 and 1.41-fold, respectively. Maximum asiaticoside
production was achieved following treatment with 0.1 mM MJ (116.8 mg/l). The
highest asiaticoside production (342.72 mg/l) was obtained after 36 days of
elicitation in cultures treated with 0.1 mM MJ and 0.025 mg/l
1-phenyl-3-(1,2,3-thidiazol-5-yl)urea (TDZ). Interestingly, MJ not only
stimulated the production of asiaticoside but also had an important role in the
senescence of C. asiatica. Although asiaticoside content did not change when TDZ
was added to medium containing an elicitor, TDZ did increase shoot growth of C.
asiatica. We discuss the interactive roles of MJ and TDZ in secondary metabolic
production and biomass in whole plants of C. asiatica.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15316748 [PubMed - indexed for MEDLINE]

49: Asia Pac J Clin Nutr. 2004 Aug;13(Suppl):S72.

Antioxidative behaviour of Malaysian plant extracts in model and food oil
systems.

Jaswir I, Hassan TH, Said MZ.

Department of Biotechnology, Faculty of Science, International Islamic
University Malaysia, Jalan Gombak 53100 Kuala Lumpur, Malaysia.

Background - 'Pegaga' (Centella Asiatica) and 'limau purut' (Citrus hystrix) are
two types of plant traditionally used in Malaysian local dishes. Recent studies
showed that pegaga and limau purut leaves not only can be used as food
ingredients, but also can benefit human health. Objective - To investigate the
antioxidative behaviour of the crude extracts of pegaga leaves, and limau purut
leaves, peels, and stems in a linoleic acid model system and in palm olein
system. Design - Antioxidant activity of these local plants were analyzed using
an oxygen consumption method and by differential scanning calorimetry (DSC). The
antioxidant activity of these plants were then compared to the activity of
rosemary and sage, two types of antioxidant commonly found in the market.
Outcomes - From the analysis using oxygen consumption method, it was found that
among the samples evaluated, pegaga leaves had the longest time to reach the 50%
oxygen in the chamber, with 90 min, meaning that this sample had the highest
level of antioxidant activity. This was followed by the extracts of limau purut
leaves (85 min), peels (60 min), and stems (39 min). Results from the DSC
analysis showed that addition of pegaga leaves and limau purut samples to the
palm olein in the system reduced the oxidation as evidenced by longer T(o) of
antioxidants-treated samples. Statistical analysis from this study showed that
there was no significant difference between T(o) of pegaga leaves and those of
rosemary and sage. This meant that the antioxidant activity of pegaga leaves was
comparable to the activities of rosemary and sage. Conclusion - The finding from
this study indicated that all samples used in this study had very good potential
to be explored as sources of natural antioxidants.

PMID: 15294565 [PubMed - as supplied by publisher]

50: J Agric Food Chem. 2004 Aug 11;52(16):5183-6.

Total phenolics and antioxidant activities of fenugreek, green tea, black tea,
grape seed, ginger, rosemary, gotu kola, and ginkgo extracts, vitamin E, and
tert-butylhydroquinone.

Rababah TM, Hettiarachchy NS, Horax R.

Department of Food Science, University of Arkansas, 2650 North Young Avenue,
Fayetteville, Arkansas 72704, USA.

The total phenolics and antioxidant activities of fenugreek, green tea, black
tea, grape seed, ginger, rosemary, gotu kola, and ginkgo extracts, vitamin E,
and tert-butylhydroquinone, were determined. Grape seed and green tea were
analyzed for their phenolic constituents using high-performance liquid
chromatography. The total phenolics of the plant extracts, determined by the
Folin-Ciocalteu method, ranged from 24.8 to 92.5 mg of chlorogenic acid
equivalent/g dry material. The antioxidant activities of methanolic extracts
determined by conjugated diene measurement of methyl linoleate were 3.4-86.3%.
The antioxidant activity of the extracts using chicken fat by an oxidative
stability instrument (4.6-10.2 h of induction time) followed a similar trend in
antioxidant activity as determined by the Folin-Ciocalteu method. Seven
phenolics in grape seed and green tea extracts were identified that ranged from
15.38 to 1158.49 and 18.3 to 1087.02 mg/100 g of extract, respectively. Plant
extracts such as green tea and grape seed extracts can be used to retard lipid
oxidation in a variety of food products.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15291494 [PubMed - indexed for MEDLINE]

51: Phytomedicine. 2004;11(4):361-5.

Preliminary immunomodulatory activities of methanol extracts of Eclipta alba and
Centella asiatica.

Jayathirtha MG, Mishra SH.

Pharmacy Department, The M.S. University of Baroda, Kalabhavan, Vadodara 390
001, India.

An attempt has been made to assess the immunomodulatory activity of methanol
extracts of whole plant of E. alba (1.6% wedelolactone) and C. asiatica (0.18%
of asiaticoside) at five dose levels (dose-response relationship) ranging from
100 to 500 mg/kg body wt. using carbon clearance, antibody titer and
cyclophosphamide immunosuppression parameters. In the case of E. alba, the
phagocytic index and antibody titer increased significantly and the F ratios of
the phagocytic index and WBC count were also significant. Regression analysis
showed linearity in patterns of the dose-response relationship, greatest in the
case of the phagocytic index, moderate in the WBC count and lowest in the
antibody titer. For C. asiatica, significant increases in the phagocytic index
and total WBC count were observed and the F ratio of the phagocytic index was
also significant. Regressed values revealed maximum linearity in the case of the
phagocytic index, moderate linearity in the total WBC count and lowest linearity
in the antibody response.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15185851 [PubMed - indexed for MEDLINE]

52: J Ethnopharmacol. 2004 Jul;93(1):105-8.

Cardioprotective activity of Hydrocotyle asiatica L. in ischemia-reperfusion
induced myocardial infarction in rats.

Pragada RR, Veeravalli KK, Chowdary KP, Routhu KV.

Pharmacology Division, Department of Pharmaceutical Sciences, Andhra University,
Visakhapatnam 530003, Andhra Pradesh, India. [email protected]

The alcoholic extract of Hydrocotyle asiatica Linn. (Hydrocotyle asiatica L.)
whole plant was evaluated for cardioprotective activity against
ischemia-reperfusion induced myocardial infarction in rats. Cardioprotective
activity was studied by measuring infarct size and estimating lipid peroxide
levels in serum and heart tissue. A lead II electrocardiogram was monitored at
various intervals throughout the experiment. A dose (100-1000 mg kg(-1))
dependent reduction in percent left ventricle necrosis (PLVN) as well as in
lipid peroxide levels was observed in rats treated with alcoholic extract of
Hydrocotyle asiatica L. orally for 7 days compared to control animals. The study
strongly suggests the cardioprotective activity of Hydrocotyle asiatica L. in
limiting ischemia-reperfusion induced myocardial injury.

Publication Types:
Comparative Study

PMID: 15182913 [PubMed - indexed for MEDLINE]

53: Zhong Yao Cai. 2003 Dec;26(12):870-3.

[Effect of total triterpenes from Centella asiatica on the depression behavior
and concentration of amino acid in forced swimming mice]

[Article in Chinese]

Chen Y, Han T, Qin L, Rui Y, Zheng H.

School of Pharmacy, Second Military Medical University, Shanghai 200433.

OBJECTIVE: To evaluate the antidepressant activity of total triterpenes from
Centella asiatica in forced swimming test. METHODS: Mice were randomly divided
into control group, model group and treatment group. The effect of total
triterpenes from Centella asiatica on the immobility time in forced swimming
mice and concentration of amino acid in mice brain tissue was observed. RESULTS:
Imipramine and total triterpenes from Centella asiatica reduced the immobility
time and ameliorated the imbalance of amino acid levels. CONCLUSION: The total
triterpenes from Centella asiatica had antidepressant activity.

Publication Types:
English Abstract
Research Support, Non-U.S. Gov't

PMID: 15058206 [PubMed - indexed for MEDLINE]

54: Life Sci. 2004 Mar 19;74(18):2237-49.

The healing effects of Centella extract and asiaticoside on acetic acid induced
gastric ulcers in rats.

Cheng CL, Guo JS, Luk J, Koo MW.

Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, 21
Sassoon Road, Pokfulam, Hong Kong, China.

In this study, the healing effects of Centella asiatica water extract (CE) and
asiaticoside (AC), an active constituent of CE, on acetic acid induced gastric
ulcers (kissing ulcers) in rats were examined. CE was prepared from Centella
asiatica dry plant and the concentration of AC in CE was quantitatively
determined with the use of high performance liquid chromatography analysis.
Different concentrations of CE and AC were orally administered to rats with
kissing ulcers. They were found to reduce the size of the ulcers at day 3 and 7
in a dose-dependent manner, with a concomitant attenuation of myeloperoxidase
activity at the ulcer tissues. Epithelial cell proliferation and angiogenesis
were on the other hand promoted. The expression of basic fibroblast growth
factor, an important angiogenic factor, was also upregulated in the ulcer
tissues in rats treated with CE or AC. These results further suggest the
potential use of Centella asiatica and its active ingredient as anti-gastric
ulcers drugs.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 14987949 [PubMed - indexed for MEDLINE]

55: Altern Med Rev. 2003 Nov;8(4):359-77.

Nutritional support for wound healing.

MacKay D, Miller AL.

Thorne Research, Inc., PO Box 25, Dover, ID 83825, USA. [email protected]

Healing of wounds, whether from accidental injury or surgical intervention,
involves the activity of an intricate network of blood cells, tissue types,
cytokines, and growth factors. This results in increased cellular activity,
which causes an intensified metabolic demand for nutrients. Nutritional
deficiencies can impede wound healing, and several nutritional factors required
for wound repair may improve healing time and wound outcome. Vitamin A is
required for epithelial and bone formation, cellular differentiation, and immune
function. Vitamin C is necessary for collagen formation, proper immune function,
and as a tissue antioxidant. Vitamin E is the major lipid-soluble antioxidant in
the skin; however, the effect of vitamin E on surgical wounds is inconclusive.
Bromelain reduces edema, bruising, pain, and healing time following trauma and
surgical procedures. Glucosamine appears to be the rate-limiting substrate for
hyaluronic acid production in the wound. Adequate dietary protein is absolutely
essential for proper wound healing, and tissue levels of the amino acids
arginine and glutamine may influence wound repair and immune function. The
botanical medicines Centella asiatica and Aloe vera have been used for decades,
both topically and internally, to enhance wound repair, and scientific studies
are now beginning to validate efficacy and explore mechanisms of action for
these botanicals. To promote wound healing in the shortest time possible, with
minimal pain, discomfort, and scarring to the patient, it is important to
explore nutritional and botanical influences on wound outcome.

Publication Types:
Review

PMID: 14653765 [PubMed - indexed for MEDLINE]

56: J Int Acad Periodontol. 2003 Oct;5(4):106-15.

Adjunctive periodontal treatment with Centella asiatica and Punica granatum
extracts. A preliminary study.

Sastravaha G, Yotnuengnit P, Booncong P, Sangtherapitikul P.

Out-Patient Department, Faculty of Dentistry, Mahidol University, Bangkok,
Thailand.

BACKGROUND: Centella asiatica and Punica granatum are medicinal herbs that have
been reported to promote tissue healing and modulate host responses. The purpose
of this study was to investigate the effects of the combined extracts from C.
asiatica and P. granatum pericarp on periodontal healing following scaling and
root planing in adult periodontitis patients. METHODS: An innovative herbal
medicament was formulated in the form of biodegradable chips for subgingival
application. Twenty patients with initial pocket depth 5-8 mm were enrolled into
the study. After baseline examination, scaling and root planing of non-target
teeth, the target teeth received scaling and root planing followed by
subgingival delivery of medicated chips in the test group and unmedicated chips
in the placebo group. Probing pocket depth, attachment level, bleeding on
probing, gingival index, and plaque index were recorded at baseline, 3 and 6
months. RESULTS: The results showed significant improvements of pocket depth and
attachment level in the test sites when compared with the placebo sites at 3
months and with the placebo and control sites at 6 months. All treatment sites
exhibited a similar trend of decreasing plaque score. However, the test sites
seemed to show slightly better percentage of bleeding on probing. CONCLUSION:
The results indicate that local delivery with C. asiatica and P. granatum
extracts plus scaling and root planing significantly reduced the clinical signs
of chronic periodontitis.

Publication Types:
Clinical Trial
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

PMID: 14604059 [PubMed - indexed for MEDLINE]

57: Carbohydr Res. 2003 Oct 31;338(22):2393-402.

Structure and potential immunological activity of a pectin from Centella
asiatica (L.) Urban.

Wang XS, Dong Q, Zuo JP, Fang JN.

Shanghai Institute of Materia Medica, Shanghai Institutes for Biological
Sciences, Chinese Academic of Sciences, 555 Zu-Chong-Zhi Road, Zhangjiang
Hi-Tech Park, Shanghai 201203, PR China.

S3A was a RG-I pectin isolated from Centella asiatica that contained Rha, Ara,
Gal, Glc and GalA in molar ratio of 1.0:0.6:1.5:0.2:1.1 and had been found to
have a backbone composed mainly of the disaccharide repeat unit,
-->4)-alpha-D-GalpA-(1-->2)-alpha-L-Rhap-(1-->. Based on methylation analysis,
NaIO4 oxidation, partial acid hydrolysis and lithium-treatment, the structural
features were elucidated. Side chains of S3A were predominantly linked to O-4 of
1,2,4-linked alpha-L-Rhap. The side chains are comprised of arabinosyl chains,
galactosyl chains, arabinogalactosyl chains and short glucosyl chains. A total
of 45% Rhap in the backbone was substituted by side chains. The arabinosyl
residues were mostly distributed in the arabinosyl side chains. According to the
immunological results of S3A and its degraded derivatives, S3A had no
immunological activity, but its derivatives had immuno-stimulating activities to
some extent.

PMID: 14572724 [PubMed - indexed for MEDLINE]

58: Planta Med. 2003 Aug;69(8):725-32.

Gene expression changes in the human fibroblast induced by Centella asiatica
triterpenoids.

Coldren CD, Hashim P, Ali JM, Oh SK, Sinskey AJ, Rha C.

Malaysia-MIT Biotechnology Partnership Program, Cambridge, MA, USA.

The molecular pathways underlying the diverse biological activity of the
triterpeniod compounds isolated from the tropical medicinal plant Centella
asiatica were studied with gene microarrays and real-time reverse transcription
polymerase chain reaction (real-time RT-PCR) to quantify the expression of 1053
human genes in human fibroblasts. Fibroblast cells grown in culture were used as
a model system to evaluate the stimulation of wound healing by titrated extract
from Centella asiatica (TECA) as well as by the four principal triterpenoid
components of Centella. TECA treatment effects the expression of genes involved
in angiogenesis and the remodeling of extracellular matrix, as well as diverse
growth factor genes. The extent of expression change of TNFAIP6, an
extracellular hyaluronan binding protein, was found to be largely
dose-dependent, to respond most strongly to the free acids asiatic acid and
madecassic acid, and to increase in expression over 48 hours of treatment. These
results show that Centella triterpenes evoke a gene-expression response
consistent with their prevailing medical uses in the treatment of connective
tissue disorders such as wound healing and microangiopathy. The identification
of genes modulated by these compounds provides the basis for a molecular
understanding of Centella's bioactivity, and opportunities for the quantitative
correlation of this activity with clinical effectiveness at a molecular level.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

PMID: 14531023 [PubMed - indexed for MEDLINE]

59: Clin Exp Pharmacol Physiol. 2003 May-Jun;30(5-6):336-42.

Effect of Centella asiatica on cognition and oxidative stress in an
intracerebroventricular streptozotocin model of Alzheimer's disease in rats.

Veerendra Kumar MH, Gupta YK.

Neuropharmacology Laboratory, Department of Pharmacology, All India Institute of
Medical Sciences, Ansari Nagar, New Delhi, India.

1. Centella asiatica, an Indian medicinal plant, has been described as
possessing central nervous system activity, such as improving intelligence. In
addition, we have demonstrated that C. asiatica has cognitive-enhancing and
anti-oxidant properties in normal rats. Oxidative stress or an impaired
endogenous anti-oxidant mechanism is an important factor that has been
implicated in Alzheimer's disease (AD) and cognitive deficits seen in the
elderly. 2. Intracerebroventricular (i.c.v.) streptozotocin (STZ) in rats has
been likened to sporadic AD in humans and the cognitive impairment is associated
with free radical generation in this model. Therefore, in the present study, the
effect of an aqueous extract of C. asiatica (100, 200 and 300 mg/kg for 21 days)
was evaluated in i.c.v. STZ-induced cognitive impairment and oxidative stress in
rats. 3. Male Wistar rats were injected with STZ (3 mg/kg, i.c.v.) bilaterally
on the days 1 and 3. Cognitive behaviour was assessed using passive avoidance
and elevated plus-maze paradigms on the days 13, 14 and 21. Rats were killed on
the day 21 for estimation of oxidative stress parameters (malondialdehyde (MDA),
glutathione, superoxide dismutase and catalase) in the whole brain upon
completion of the behavioural task. 4. Rats treated with C. asiatica showed a
dose-dependent increase in cognitive behaviour in both paradigms. A significant
decrease in MDA and an increase in glutathione and catalase levels were observed
only in rats treated with 200 and 300 mg/kg C. asiatica. 5. The present findings
indicate that an aqueous extract of C. asiatica is effective in preventing the
cognitive deficits, as well as the oxidative stress, caused by i.c.v. STZ in
rats.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12859423 [PubMed - indexed for MEDLINE]

60: Pharmazie. 2003 Jun;58(6):381-4.

An improved HPLC method for quantitative determination of six triterpenes in
Centella asiatica extracts and commercial products.

Schaneberg BT, Mikell JR, Bedir E, Khan IA.

National Center for Natural Products Research, School of Pharmacy, The
University of Mississippi, MS 38677, USA.

An improved HPLC qualitative and quantitative method of six triterpenes
(asiaticoside, madecassoside, asiatic acid, madecassic acid, terminolic acid,
and asiaticoside-B) in Centella asiatica (raw plant material and preparations)
is described in this paper. After 50 minutes the six active triterpenes were
separated and detected in the methanolic extract at a limit of 0.01 microg/ml.
The method uses a Phenomenex Aqua 5mu C18 (200 A) column as the stationary
phase, a gradient mobile phase of water (0.1% TFA), acetonitrile (0.1% TFA), and
methyl tert-butyl ether (0.1% TFA), and UV detection at 206 nm. The correlation
coefficients for the calibration curves and the recovery rates ranged from 0.995
to 0.999 and from 98.39% to 100.02%, respectively. The qualitative and
quantitative results are discussed.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 12856998 [PubMed - indexed for MEDLINE]

61: Int J Dermatol. 2003 Jul;42(7):558-60.

Facial linear focal elastosis: a case report.

Inaloz HS, Kirtak N, Karakok M, Ozgoztasi O.

Gaziantep University Medical Faculty, Research and Application Hospital,
Gaziantep, Turkey. [email protected]

BACKGROUND: Linear focal elastosis is an uncommon disorder that clinically shows
band-like stria and a histological focal increase in elastic fibers. The
disorder preferentially affects men after the age of 60 years and occurs on the
lower back. The pathogenesis of linear focal elastosis is still somewhat of an
enigma. METHOD: A 50-year-old farmer presented with an unusual linear lesion on
the left side of his chin. The patient was frequently exposed to sun because of
fieldwork for a period of more than 40 years. RESULTS: Skin biopsy specimen
revealed a massive abnormal collagen deposition extending from the subpapillary
dermis to the lower dermis with numerous wavy bundles of fibers. Elastin van
Gieson stain for elastic fibers showed that abnormal elastic fibers were
increased within a massive abnormal collagen deposition. Diagnosis of facial
linear focal elastosis was made after clinicopathological correlation.
CONCLUSION: Facial involvement of linear focal elastosis has not been reported
previously in the literature. It has been suggested that sunlight has a minor
role in the development of elastotic change in linear focal elastosis. However,
our patient was a farmer and was exposed to sunlight frequently for a period of
more than 40 years, suggesting that ultraviolet radiation may play a role in the
pathogenesis of linear focal elastosis.

Publication Types:
Case Reports

PMID: 12839610 [PubMed - indexed for MEDLINE]

62: Fitoterapia. 2003 Jul;74(5):431-4.

Anti-oxidant activity of Centella asiatica on lymphoma-bearing mice.

Jayashree G, Kurup Muraleedhara G, Sudarslal S, Jacob VB.

Applied Biochemistry Laboratory, School of Biosciences, MG University, PD Hills
(PO), Kottayam, Kerala 686560, India. [email protected]

Oral treatment with 50 mg X kg(-1) day(-1) of crude methanol extract of Centella
asiatica for 14 days significantly increased the anti-oxidant enzymes, like
superoxide dismutase (SOD), catalase and glutathione peroxidase (GSHPx), and
anti-oxidants like glutathione (GSH) and ascorbic acid decreased in
lymphoma-bearing mice.

PMID: 12837356 [PubMed - indexed for MEDLINE]

63: Pharmacol Biochem Behav. 2003 Feb;74(3):579-85.

Effect of Centella asiatica on pentylenetetrazole-induced kindling, cognition
and oxidative stress in rats.

Gupta YK, Veerendra Kumar MH, Srivastava AK.

Neuropharmacology Laboratory, Department of Pharmacology, All India Institute of
Medical Sciences, Ansari Nagar, 110029, New Delhi, India. [email protected]

Cognitive impairment in epileptics may be a consequence of the epileptogenic
process as well as antiepileptic medication. Thus, there is a need for drugs,
which can suppress epileptogenesis as well as prevent cognitive impairment. In
the present study, the effect of aqueous extract of Centella asiatica (CA) (100
and 300 mg/kg), an Indian medicinal plant known to possess antiepileptic,
cognitive-enhancing and antioxidant property, was evaluated on the course of
kindling development, kindling-induced learning deficit and oxidative stress
markers in pentylenetetrazole (PTZ) kindled rats. Male Wistar rats were injected
PTZ (30 mg/kg ip) once every alternate day (48+/-2 h) until the development of
the kindling. Passive avoidance test and spontaneous locomotor activity were
carried out 24 and 48 h after the last administration of PTZ, while the
oxidative stress parameters (malondialdehyde [MDA] and glutathione) were carried
out in the whole brain upon completion of the behavioral assessment. The
administration of CA (300 mg/kg orally) decreased the PTZ-kindled seizures and
showed improvement in the learning deficit induced by PTZ kindling as evidenced
by decreased seizure score and increased latencies in passive avoidance
behavior. However, low dose of the CA (100 mg/kg) showed improvement only in the
learning deficit due to the kindling and failed to improve the seizure score.
The findings suggest the potential of aqueous extract of CA as adjuvant to
antiepileptic drugs with an added advantage of preventing cognitive impairment.

PMID: 12543222 [PubMed - indexed for MEDLINE]

64: Zhongguo Zhong Yao Za Zhi. 2000 Apr;25(4):199-202.

[Resources distribution and pharamacognostic identification of Centella asiatica
(L.) urban produced in China]

[Article in Chinese]

Chen Y, Qin LP, Zheng HC, Zhang ZH.

College of Pharmacy, Second Military Medical University, Shanghai 200433, China.

OBJECTIVE: To investigate the resources distribution and morphological histology
of Centella asiatica distributed in China, and offer evidences for exploiting
the plant resources and drafting the quality standards. METHOD: Sample
collection, document investigation and microscopic section observation. RESULT:
A table of resources distribution was worked out, the medicinal properties and
the microscopic characteristics of the stem, leaf and stipe were described.
CONCLUSION: This study supports the viewpoint of Urban and can be used as a
reference for the quality standard of Centella asiation.

Publication Types:
English Abstract
Research Support, Non-U.S. Gov't

PMID: 12512431 [PubMed - indexed for MEDLINE]

65: Phytother Res. 2002 Dec;16(8):785-6.

Radioprotection of Swiss albino mouse by Centella asiatica extract.

Sharma J, Sharma R.

Department of Zoology, University of Rajasthan, Jaipur 302004, India.

Centella asiatica, has a considerable reputation in the Indian system of
medicine. It is a rasayan (general tonic), brain tonic, improves memory and
strengthens the CNS. In view of its multifarious uses, the plant extract was
tested for its radioprotective properties. A sublethal dose of Co 60 gamma
radiation, i.e. 8 Gy was selected for the purpose. Animals were divided into two
groups. The whole bodies were irradiated with Co 60 gamma radiation externally,
with and without drug extract. The drug extract was given orally at different
doses and for different time intervals. The dose that was most effective against
radiation was 100 mg/kg body weight. This dose increased the survival time of
the mice significantly. Body weight loss of the animals in the drug treated
group was significantly less in comparison with the animals that were given
radiation only. The causes and mechanism of protection and other aspects need
further investigations. Copyright 2002 John Wiley & Sons, Ltd.

PMID: 12458490 [PubMed - indexed for MEDLINE]

66: J Cosmet Sci. 2002 Jul-Aug;53(4):209-18.

An in vitro, ex vivo, and in vivo demonstration of the lipolytic effect of
slimming liposomes: An unexpected alpha(2)-adrenergic antagonism.

Tholon L, Neliat G, Chesne C, Saboureau D, Perrier E, Branka JE.

Coletica, 32 rue Saint Jean de Dieu, 69007 Lyon, France.

Most of the slimming products already developed for cosmetic applications did
not result from strategies that integrate whole lipolysis-regulating mechanisms.
We thus focused our attention on a more complete integration of these mechanisms
and we developed slimming liposomes (SLC) containing two micro-circulation
activators, i.e., esculoside and Centella asiatica extracts, one
phosphodiesterase inhibitor, i.e., caffeine, and one fatty acid-beta oxidation
activator, i.e., L-carnitine. The validity of our approach was assessed through
(a) in vitro tests demonstrating that SLC induced a dramatic increase in the
cyclic adenosine monophosphate (cAMP) content in human adipocytes, with a
subsequent rise in the nonesterified fatty acids (NEFA) content of human
adipocyte incubation medium, and (b) in vivo studies showing that SLC could
provide an actual potent slimming effect on human volunteers. Moreover, we give
here, through binding experiments, the unambiguous demonstration that SLC is
able to antagonize the alpha(2)-adrenergic receptor that is known to reduce
intracellular AMPc content and, subsequently, to down-regulate lipolysis. This
alpha(2)-adrenergic antagonism has never been reported for any component of SLC,
and this work is the first demonstration of the alpha(2)-adrenergic antagonism
of such a combination of active liposome compounds.

Publication Types:
Clinical Trial
Controlled Clinical Trial
In Vitro

PMID: 12219247 [PubMed - indexed for MEDLINE]

67: Phytother Res. 2002 Aug;16(5):440-4.

In vitro anti-hepatoma activity of fifteen natural medicines from Canada.

Lin LT, Liu LT, Chiang LC, Lin CC.

Department of Microbiology and Immunology, McGill University, Canada.

Fifteen crude drugs, Stellaria media Cyrill. (Caryophyllaceae), Calendula
officinalis L. (Compositae), Achillea millefolium L. (Compositae), Verbascum
thapsus L. (Scrophulariaceae), Plantago major L. (Plantaginaceae), Borago
officinalis L. (Boraginaceae), Satureja hortensis L. (Labiatae), Coptis
groenlandica Salisb. (Ranunculaceae), Cassia angustifolia Vahl. (Leguminosae),
Origanum majorana L. (Labiatae), Centella asiatica L. (Umbelliferae),
Caulophyllum thalictroides Mich. (Berberidaceae), Picea rubens Sargent.
(Pinaceae), Rhamnus purshiana D.C. (Rhamnaceae) and Hibiscus sabdariffa L.
(Malvaceae), which have been used as folk medicine in Canada, were evaluated for
their anti-hepatoma activity on five human liver-cancer cell lines, i.e.
HepG2/C3A, SK-HEP-1, HA22T/VGH, Hep3B and PLC/PRF/5. The samples were examined
by in vitro evaluation for their cytotoxicity. The results showed that the
effects of crude drugs on hepatitis B virus genome-containing cell lines were
different from those against non hepatitis B virus genome-containing cell lines.
C. groenlandica was observed to be the most effective against the growth of all
five cell lines and its chemotherapeutic values will be of interest for further
studies. Copyright 2002 John Wiley & Sons, Ltd.

PMID: 12203264 [PubMed - indexed for MEDLINE]

68: J Ethnopharmacol. 2002 Feb;79(2):253-60.

Effect of different extracts of Centella asiatica on cognition and markers of
oxidative stress in rats.

Veerendra Kumar MH, Gupta YK.

Department of Pharmacology, Neuropharmacology Laboratory, All India Institute of
Medical Sciences, Ansari Nagar, New Delhi 110 029, India.

Centella asiatica, a plant mentioned in Indian literature has been described to
possess CNS effects such as stimulatory-nervine tonic, rejuvenant, sedative,
tranquilizer and intelligence promoting property. In the present study aqueous,
methanolic and chloroform extracts of C. asiatica were investigated for their
effect on cognitive functions in rats. Male Wistar rats of 200-250 g were used
to study the effect on learning and memory by using shuttle box, step through,
step down and elevated plus maze paradigms. Only the aqueous extract of whole
plant (200 mg/kg for 14 days) showed an improvement in learning and memory in
both shuttle box and step through paradigms. Therefore, further experiments were
conducted with aqueous extract using 100, 200 and 300 mg/kg doses in different
paradigms of learning and memory. All doses of aqueous extract increased the
number of avoidances in shuttle box and prolonged the step through latency in
step through apparatus in a dose dependent manner, while only two doses 200 and
300 mg/kg of aqueous extract showed significant increase in the step down
latency in step down apparatus and transfer latency (TL) in elevated plus maze.
Among doses of aqueous extract tested on oxidative stress parameters, only 200
and 300 mg/kg showed a significant decrease in the brain levels of
malondialdehyde (MDA) with simultaneous significant increase in levels of
glutathione. There was a significant increase in the levels of catalase at the
300 mg/kg but no significant change in superoxide dismutase (SOD) levels were
observed. The present findings indicate that the aqueous extract of C. asiatica
has cognitive enhancing effect and an antioxidant mechanism is involved.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11801389 [PubMed - indexed for MEDLINE]

69: Res Commun Mol Pathol Pharmacol. 2000 Jul-Aug;108(1-2):75-86.

Asiatic acid derivatives protect cultured cortical neurons from
glutamate-induced excitotoxicity.

Lee MK, Kim SR, Sung SH, Lim D, Kim H, Choi H, Park HK, Je S, Ki YC.

College of Pharmacy, Seoul National University, Korea.

Asiatic acid, a triterpene of Centella asiatica (L.) Urban (Umbelliferae), has
been patented as a treatment for dementia and an enhancer of cognition by the
Hoechst Aktiengesellschaft (EP 0 383 171 A2). We modified the chemical structure
of asiatic acid and obtained 36 derivatives of asiatic acid in an attempt to
prepare neuroprotective compounds that were more efficacious than asiatic acid
itself. The neuroprotective activities of these derivatives were evaluated using
primary cultures of rat cortical neurons insulted with the neurotoxin,
glutamate, as an in vitro screening system. Among the semi-synthesized
derivatives, three derivatives significantly mitigated the neurotoxicity induced
by glutamate in this screening system. The neuroprotective activities of these 3
derivatives appeared to be more powerful than that of asiatic acid itself. These
3 derivatives significantly attenuated decreases in the levels of glutathione,
glutathione peroxidase and other enzymes, which participate in the cellular
defense mechanisms blunting oxidative stress. Furthermore, they significantly
reduced the overproduction of NO induced by glutamate. These results showed that
these derivatives of asiatic acid exerted significant neuroprotective effects on
cultured cortical cells by their potentiation of the cellular oxidative defense
mechanism. Therefore, these agents may prove to be efficacious in protecting
neurons from the oxidative damage caused by exposure to excess glutamate.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11758977 [PubMed - indexed for MEDLINE]

70: Angiology. 2001 Oct;52 Suppl 2:S9-13.

Total triterpenic fraction of Centella asiatica in chronic venous insufficiency
and in high-perfusion microangiopathy.

Incandela L, Cesarone MR, Cacchio M, De Sanctis MT, Santavenere C, D'Auro MG,
Bucci M, Belcaro G.

Vascular Unit, Ealing Hospital, London, UK.

Total triterpenic fraction of Centella asiatica (TTFCA) is effective in
improving venous wall alterations in chronic venous hypertension and in
protecting the venous endothelium. TTFCA is active on connective tissue
modulation, improves the synthesis of collagen and other tissue proteins by
modulating the action of fibroblasts in the vein wall, and stimulates collagen
remodeling in and around the venous wall. This is due to the modulating action
of TTFCA on fibroblasts as shown by experiments on the growth of human embryonal
fibroblasts. TTFCA has a moderate in-vitro and in-vivo stimulating effect on
collagen synthesis and, at higher dosages, an inhibition on the synthesis of
collagen and acid mucopolysaccharides. Studies have indicated the role of TTFCA
on the synthesis of specific venous wall elements by cell cultures of human
embryonal fibroblasts. The tissue-stimulating action is shown by the increased
collagen production independent from the stimulation of cell proliferation (this
differentiates the action of TTFCA from cell growth factors). TTFCA is active on
the microcirculation in venous and diabetic microangiopathy. Signs and symptoms
of venous hypertension and edema are improved by treatment. The remodeling on
collagen synthesis could be one of the possible mechanisms of actions of TTFCA
in the remodeling of echolucent (soft; therefore, with risk of thrombosis and
embolization) plaques at the carotid and femoral bifurcation. This compound is
safe and well tolerated. In conclusion, several actions of TTFCA in vascular
diseases makes the use of this compound very interesting in venous and arterial
problems.

Publication Types:
Review

PMID: 11666128 [PubMed - indexed for MEDLINE]

71: Angiology. 2001 Oct;52 Suppl 2:S69-73.

Modification of the echogenicity of femoral plaques after treatment with total
triterpenic fraction of Centella asiatica: a prospective, randomized,
placebo-controlled trial.

Incandela L, Belcaro G, Nicolaides AN, Cesarone MR, De Sanctis MT, Corsi M,
Bavera P, Ippolito E, Griffin M, Geroulakos G, Sabetai M, Ramaswami G, Veller M.

Irvine Vascular Laboratory, St Mary's Hospital at Imperial College, London, UK.

The aim of this study was to evaluate whether TTFCA (total triterpenic fraction
of Centella asiatica), was effective, by modulating collagen production, in a
period of 12 months, increasing the echogenicity of echolucent plaques at the
femoral bifurcation. Hypoechoic atherosclerotic plaques have been found to be
associated with an increased evidence of cerebrovascular events. In this type of
plaques stromal composition is limited as the collagen component is generally
very low; the plaque composition is mainly due to lipid accumulation or
thrombosis. The aim of this study was the evaluation of echogenicity of
hyperechoic plaques and how it could be modified by a drug acting on the
modulation of collagen synthesis. Antiplatelet agents were used in all patients;
cholesterol-lowering agents were used in 34% of patients in the treatment group
and in 36% in the placebo group. TTFCA was used at the dose of 60 mg thrice
daily (oral tablets). Of the 60 included subjects 26 completed the study in the
treatment group and 24 in the placebo group. At inclusion the average GSM in the
treatment group was 14 (SD 3) and 14.3 (SD 3) in controls. At 12 months GSM was
increased up to 22.8 (SD 4) in the treatment group and it was 15 (SD 3) in
controls. Considering texture no significant changes were observed in controls
while a qualitative increase in homogenicity was observed in the TTFCA group.
Plaque size measured at the beginning and at the end of the study showed a
median increase in size, in controls (23%; range 0%-44%); it was unchanged in
the TTFCA group (variation 7%; 4%-26%). In conclusion in the treatment group
plaques increased in echogenicity and in homogenicity; size and stenosis
remained unchanged. Modulating the scarring process within echolucent plaques
(low echogenicity, high echolucency, with a very low collagen/stromal
component), possibly by collagen modulation, makes plaques more stable. This has
been achieved and documented in the present study by an increase in the
gray-scale median (plaques become more echogenic, more 'white'). The variation
in GSM is generally associated with a lower risk of wall thrombosis, rupture and
embolization. These observations indicate a positive action of TTFCA on the
stabilization of hypoechoic, low-density femoral plaques.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 11666127 [PubMed - indexed for MEDLINE]

72: Angiology. 2001 Oct;52 Suppl 2:S61-7.

Total triterpenic fraction of Centella asiatica in the treatment of venous
hypertension: a clinical, prospective, randomized trial using a combined
microcirculatory model.

Incandela L, Belcaro G, De Sanctis MT, Cesarone MR, Griffin M, Ippolito E, Bucci
M, Cacchio M.

Irvine Vascular Laboratory, St Mary's Hospital and Imperial College, London, UK.

A single-blind, placebo-controlled, randomized study was performed on the
effects of different doses of the total triterpenic fraction of Centella
asiatica (TTFCA) in patients with venous hypertensive microangiopathy. A
combined microcirculatory model that considers laser Doppler flowmetry (LDF) and
transcutaneous oxygen (PO2), transcutaneous carbon dioxide tension (PCO2)
measurements was combined with the symptom evaluation. LDF tests included the
baseline resting flow, the venoarteriolar reflex, and the variation of flow
related to the temperature increase. All tests provided a significant difference
between drug-treated groups and the placebo group, thereby allowing a
distinction to be made between the higher (120 mg daily) and the lower (60 mg
daily) dose of TTFCA. Transcutaneous PO2-PCO2 measurements were significantly
modified by drug treatments, while no variation could be detected in the placebo
group. Important symptomatologic effects (evaluated by subjective scores)
followed TTFCA administration, especially at the higher dose level, while no
effect was obtained with placebo. The trend of symptom evaluation paralleled the
results of objective tests of our microcirculatory model, providing evidence
that this model can reveal effects of venoactive drugs on venous hypertensive
microangiopathy. TTFCA displays a significant activity. Doses as high as 120 mg
daily may be safely used in venous hypertension.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 11666126 [PubMed - indexed for MEDLINE]

73: Angiology. 2001 Oct;52 Suppl 2:S55-9.

Treatment of edema and increased capillary filtration in venous hypertension
with total triterpenic fraction of Centella asiatica: a clinical, prospective,
placebo-controlled, randomized, dose-ranging trial.

De Sanctis MT, Belcaro G, Incandela L, Cesarone MR, Griffin M, Ippolito E,
Cacchio M.

Irvine Vascular Laboratory, St Mary's Hospital and Imperial College, London, UK.

The variation of capillary filtration rate (CFR), ankle circumference (AC), and
ankle edema (AE) was evaluated in three groups of patients with venous
hypertension (ambulatory venous pressure >42 mm Hg) and in a group of normal
subjects before and after treatment for 4 weeks with total triterpenic fraction
of Centella asiatica (TTFCA), a venoactive drug acting on the microcirculation
and on capillary permeability. Group A (20 patients)was treated with TTFCA 60 mg
thrice daily, group B (20 patients) was treated with 30 mg thrice daily; group C
(12 patients) was treated with placebo; and group D (10 normal subjects) was
treated with TTFCA 60 mg thrice daily in a randomized study. Capillary
filtration rate was assessed by venous occlusion plethysmography, ankle edema by
a new system called AET (ankle edema tester). Subjective symptoms of venous
hypertension were assessed by an analogue scale line considering four symptoms:
swelling sensation, restless lower extremity, pain and cramps, and tiredness.
CFR, AC, and AE were significantly higher in patients in comparison with normal
subjects. After 4 weeks of TTFCA treatment, there was a significant decrease of
CFR, AC, and AET time in patients. This was also greater in the higher dose
group. No significant change was observed in the placebo group and in normal
subjects treated with TTFCA. Symptoms were also significantly improved in the
two groups treated with the active drug according to the dose. No significant
changes were observed in the placebo group. In conclusion, the improvement of
signs and symptoms by TTFCA observed in patients with venous hypertension was
well correlated with the improvement of CFR and ankle edema. Dose ranging showed
that 180 mg/day is more effective in improving symptoms and CFR.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 11666125 [PubMed - indexed for MEDLINE]

74: Angiology. 2001 Oct;52 Suppl 2:S49-54.

Evaluation of treatment of diabetic microangiopathy with total triterpenic
fraction of Centella asiatica: a clinical prospective randomized trial with a
microcirculatory model.

Cesarone MR, Incandela L, De Sanctis MT, Belcaro G, Bavera P, Bucci M, Ippolito
E.

Irvine Vascular Laboratory, St Mary's Hospital and Imperial College, London, UK.

Fifty patients with diabetic microangiopathy were studied by laser Doppler
flowmetry (measuring skin blood flow at rest) (RF) and the venoarteriolar
response (VAR), by transcutaneous PO2 and PCO2 measurements, and by capillary
permeability evaluation (rate of ankle swelling [RAS]). Thirty of these patients
were treated for 6 months with total triterpenic fraction of Centella asiatica
(TTFCA) (60 mg twice daily), a drug active on microcirculation and capillary
permeability. A control group of ten patients was treated with placebo and
another group of ten patients was left without treatment thus acting as a second
control group. After six months there were no significant changes in the two
control groups. There was a significant improvement of microcirculatory
parameter in patients treated with TTFCA. RF (abnormally increased at the
beginning of the treatment) decreased, and the VAR (impaired at the beginning of
the study) improved. PO2 increased and PCO2 decreased the abnormally increased
capillary permeability was also improved (decreased). According to these data,
TTFCA is useful in diabetic microangiopathy by improving microcirculation and
decreasing capillary permeability. Also TTFCA protects against the deterioration
of microcirculation due to diabetic microangiopathy.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 11666124 [PubMed - indexed for MEDLINE]

75: Angiology. 2001 Oct;52 Suppl 2:S45-8.

Microcirculatory effects of total triterpenic fraction of Centella asiatica in
chronic venous hypertension: measurement by laser Doppler, TcPO2-CO2, and leg
volumetry.

Cesarone MR, Belcaro G, Rulo A, Griffin M, Ricci A, Ippolito E, De Sanctis MT,
Incandela L, Bavera P, Cacchio M, Bucci M.

Irvine Vascular Laboratory, St Mary's Hospital and Imperial College, London, UK.

The aim of this prospective, randomized study was to demonstrate whether an oral
preparation of TTFCA was effective in improving the microcirculation and edema
(leg volume) in venous microangiopathy. Forty patients with venous hypertension
were included. Treatment was prescribed for 6 weeks (tablets, 60 mg twice
daily). Patients were randomized into a treatment and a placebo group. There
were 20 patients in each group. In the treatment group the mean age was 42 (SD
7; M:F = 10:10); in the placebo group, the mean age was 40 (SD 9; M:F = 10:10).
Tolerability and compliance were very good; there were no dropouts. At inclusion
there were no differences between placebo and treatment group. After treatment
there was a decrease in resting flux (29%) and an improvement (increase) in
venoarteriolar response (52%); PO2 was increased (7.2%) and PCO2 decreased
(9.6%). There was an important decrease in leg volume (66 mL decrease; 1.3%
volume variation). The difference in flux, O2-CO2 and volume parameters were
significant and clinically important at 6 weeks in the treatment group. In
conclusion, TTFCA improves microcirculation and leg volume in venous
hypertension. The effects of TTFCA are observed even in a limited sample of
patients.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 11666123 [PubMed - indexed for MEDLINE]

76: Angiology. 2001 Oct;52 Suppl 2:S33-7.

Flight microangiopathy in medium- to long-distance flights: prevention of edema
and microcirculation alterations with total triterpenic fraction of Centella
asiatica.

Cesarone MR, Incandela L, De Sanctis MT, Belcaro G, Geroulakos G, Griffin M,
Lennox A, Di Renzo AD, Cacchio M, Bucci M.

Irvine Laboratory, St Mary's Hospital at Imperial College, London, UK.

The aim of this study was the evaluation of microcirculatory alterations
associated with edema in passengers travelling for more than 3 hours and the
study of the effects of TTFCA (total triterpenic fraction of Centella asiatica)
on the development of microcirculation alterations and edema, in a prospective,
randomized study. Laser Doppler flowmetry (LDF), transcutaneous PO2 and PCO2,
rate of ankle swelling (RAS) were used. Subjects were randomized after informed
consent into two groups: one control group (no drug or other treatment), and a
treatment group (TTFCA 60 mg thrice daily for 2 days before the flight, the day
of the flight, and for another day after the flight). Inclusion criteria were
age range between 30 and 50, mild-moderate superficial venous disease with
varicose veins. Subjects traveled in economy class. In controls there was a
progressive increase in CO2, RAS, and edema score and a progressive decrease in
flux (RF) and venoarteriolar response with flying time. The variations in all
parameters were milder (p>0.05) in the TTFCA group. RAS and edema were
significantly lower in the TTFCA-treated group (p<0.025). The progressive
increase in RAS, PCO2, and the decrease in VAR and O2 were linearly associated
with flight time (up to 10 hours). These results are very interesting and
indicate an option for patients prone to edema and microcirculation disturbances
during long flights.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 11666121 [PubMed - indexed for MEDLINE]

77: Angiology. 2001 Oct;52 Suppl 2:S27-31.

Treatment of diabetic microangiopathy and edema with total triterpenic fraction
of Centella asiatica: a prospective, placebo-controlled randomized study.

Incandela L, Belcaro G, Cesarone MR, De Sanctis MT, Nargi E, Patricelli P, Bucci
M.

Irvine Vascular Laboratory, St Mary's Hospital and Imperial College, London, UK.

The aim of this study was to demonstrate in a prospective, placebo-controlled,
randomized study, whether total triterpenic fraction of Centella asiatica
(TTFCA) is effective in improving the microcirculation in diabetic
microangiopathy and neuropathy, Patients with severe diabetic microangiopathy,
neuropathy, and edema; patients with microangiopathy without neuropathy; and
healthy subjects were included. Microangiopathy was defined by laser Doppler and
capillary filtration (rate on ankle swelling). Inclusion criteria were increase
in resting flux and rate of ankle swelling; decrease in venoarteriolar response
(VAR) and alteration in flux increase with temperature. Patients were
randomized: the treatment group received TTFCA (tablets, 60 mg twice daily for
12 months); those in the placebo group received similar tablets. Healthy
controls were followed up as a reference. Groups were comparable; there were no
dropouts. There were no differences in the treatment and placebo groups at
inclusion. Treatment was well tolerated; no side effects were reported. No
variations were observed in normals at 12 months. In the neuropathy A-group,
decreases (p<0.05) in RF and RAS were observed in the two treatment groups. The
decrease in RAS was associated with a decrease in edema (p<0.05) in both
treatment groups. The differences in flux (38%) and in VAR (38%) were associated
with a decrease (28%) in the rate of ankle swelling (p<0.05). In patients
without neuropathy (B-group) the decrease in flux was 22%, the VAR increased
22.7%, and the RAS decreased 9.5% at 12 months. The variations in normals and
the progressive deterioration observed in untreated patients in both groups
indicates the difference between treatment and placebo. In conclusion, the
decrease in capillary filtration and edema is associated with symptomatic
improvement. The action on edema is beneficial for the evolution of neuropathy.
The effects of TTFCA on flux, RAS, and edema are important in early stages of
microangiopathy to avoid progression to clinical stages.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 11666119 [PubMed - indexed for MEDLINE]

78: Angiology. 2001 Oct;52 Suppl 2:S19-25.

Increase in echogenicity of echolucent carotid plaques after treatment with
total triterpenic fraction of Centella asiatica: a prospective,
placebo-controlled, randomized trial.

Cesarone MR, Belcaro G, Nicolaides AN, Geroulakos G, Bucci M, Dugall M, De
Sanctis MT, Incandela L, Griffin M, Sabetai M.

Irvine Vascular Laboratory, St Mary's Hospital and Imperial College, London, UK.

The aim of this study was to evaluate whether total triterpenic fraction of
Centella asiatica (TTFCA), was effective in modulating collagen production over
12 months, by producing an increase in echogenicity in echolucent carotid
plaques. Part I was a pilot study aimed at evaluating the effects of TTFCA on
different types of plaques. Part II was a prospective, randomized,
placebo-controlled trial aimed at evaluating the effects of TTFCA on
hypoechoic-echolucent plaques. The sonographic examination of carotid plaques
was made with high-resolution ultrasound. Capturing, digital image processing,
and normalization were standardized, interobserver, intrascanner, gain-level
variability were standardized using as reference blood (black) for the most
echolucent parts of the plaque and the adventitia (white) as the most echogenic
part. Normalization of echo texture was obtained and plaque characterization
differentiated echo-texture of plaque associated with events and those that did
not cause embolization, thrombosis, or cardiovascular events. After identifying
plaques at higher risk, patients were treated with TTFCA (oral tablets, 60 mg,
thrice daily for 12 months) to evaluate whether this compound, by modulating
collagen synthesis, could increase the echogenicity and therefore the stability
of echolucent plaques. Part II was aimed at evaluating the effects of TTFCA on
hypoechoic-echolucent plaques. Asymptomatic patients with echolucent plaques
(GSM<18) were treated with TTFCA (60 mg, oral tablets three times daily for 12
months) or with comparable placebo after informed consent. All patients were
also treated with antiplatelet agents. In part 1, at inclusion the GSC in the
hypoechoic group was 15 (range, 12-18) while in the hyperechoic group it was 26
(range, 24-31); at 6 months it was increased in the hypoechoic group and at 12
months the increase was significant (19.5; p<0.05). There was a minor increase
in GSM in the hyperechoic group (30; ns). In part II in the treatment group
there was a significant difference in GSM (increase) at 12 months (p<0.05),
improvement in texture (p<0.05) and a nonsignificant decrease in stenosis. No
changes were observed in the placebo group. Events were observed in 6.5% of
patients in the TTFCA group and in 11% in the control group (p<0.05). In
conclusion these observations suggest a positive action of TTFCA on the
stabilization of hypoechoic, low-density carotid plaques.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 11666118 [PubMed - indexed for MEDLINE]

79: Angiology. 2001 Oct;52 Suppl 2:S15-18.

Effects of the total triterpenic fraction of Centella asiatica in venous
hypertensive microangiopathy: a prospective, placebo-controlled, randomized
trial.

Cesarone MR, Belcaro G, De Sanctis MT, Incandela L, Cacchio M, Bavera P,
Ippolito E, Bucci M, Griffin M, Geroulakos G, Dugall M, Buccella S, Kleyweght S,
Cacchio M.

Irvine Vascular Laboratory, St Mary's Hospital and Imperial College, London, UK.

The aim of this study was to demonstrate whether total triterpenic fraction of
Centella asiatica (TTFCA), was effective in improving the microcirculation in
venous hypertension and microangiopathy. Forty patients with severe venous
hypertension, ankle swelling, lipodermatosclerosis were included. After informed
consent, patients were randomized into a treatment and a placebo group: those in
the treatment group received TTFCA (tablets, 60 mg, twice daily for 8 weeks).
The two groups of subjects were comparable for age and sex distribution. The
mean age was 48 years (SD 9; M:F= 11:11) in the treatment group (22 patients)
and 47.6 (SD 7; M:F= 10:8) in the placebo group (18 patients). There were no
differences between placebo and treatment group at inclusion; there was no
change between inclusion and measurements at 8 weeks in the placebo group. A
decrease (p < 0.05) in RF (flux at rest) and RAS (rate of ankle swelling) were
observed in the treatment group. The decrease in capillary filtration was
associated with improvement in signs and symptoms (p < 0.05). The difference in
flux, signs and symptoms, and filtration was clinically important at 8 weeks. No
side effects were observed. In conclusion venous microangiopathy was improved by
TTFCA treatment.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 11666117 [PubMed - indexed for MEDLINE]

80: Chem Pharm Bull (Tokyo). 2001 Oct;49(10):1368-71.

Medicinal foodstuffs. XXVII. Saponin constituents of gotu kola (2): structures
of new ursane- and oleanane-type triterpene oligoglycosides, centellasaponins B,
C, and D, from Centella asiatica cultivated in Sri Lanka.

Matsuda H, Morikawa T, Ueda H, Yoshikawa M.

Kyoto Pharmaceutical University, Japan.

Ursane- and oleanane-type triterpene oligoglycosides, centellasaponins B, C, and
D, were isolated from the aerial parts of Centella asiatica (L.) Urban
cultivated in Sri Lanka together with madecassoside, asiaticoside, asiaticoside
B, and sceffoleoside A. The chemical structures of centellasaponins B, C, and D
were determined on the basis of chemical and physicochemical evidence to be
madecassic acid 28-O-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside,
madasiatic acid
28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyr
anoside, and 3beta,6beta,23-trihydroxyolean-12-en-28-oic acid
28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyr
anoside, respectively.

PMID: 11605675 [PubMed - indexed for MEDLINE]

81: Food Chem Toxicol. 2001 Nov;39(11):1045-53.

Evaluation of the cytotoxicity, mutagenicity and antimutagenicity of emerging
edible plants.

Yen GC, Chen HY, Peng HH.

Department of Food Science, National Chung Hsing University, 250 Kuokuang Road,
Taichung 40227, Taiwan. [email protected]

This study evaluates the toxic, mutagenic and antimutagenic effects of emerging
edible plants that are consumed as new leafy vegetables in Taiwan. Among eight
plant extracts, only the extracts of Sol (Solanum nigrum L.) showed cytotoxicity
to Salmonella typhimurium TA100 in the absence of S9 mix. The toxicity of
extracts from different parts of the Sol plant, such as leaf and stem, immature
fruit and mature fruit, towards S. typhimurium TA100 and human lymphocytes was
also assayed. The immature fruit extracts of Sol exhibited strong cytotoxicity
with dose dependence and induced significant DNA damage in human lymphocytes
based on the comet assay. However, no mutagenicity was found in eight plant
extracts to TA98 or TA100 either with or without the S9 mixture. Sol and Sec
[Sechium edule (Jacq.) Swartz] extracts showed the strongest inhibitory effect
towards the mutagenicity of 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) in S.
typhimurium TA98 and TA100; the ID(50) was less then 1 mg/plate. Cra
[Crassocephalum creidioides (Benth.) S. Moore] extracts also expressed moderate
antimutagenic activities towards IQ and benzo[a]pyrene (B[a]P) either in TA98 or
in TA100; the ID(50) was 1.63-2.41 mg/plate. The extracts from Bas (Basella alba
L.), Bou (Boussingaultia gracilis Miers var. pseudobaselloides Bailey), Cen
(Centella asiatica L. Urban), Cor (Corchorus olitorius L.) and Por (Portulaca
oleracea L.) showed weak to moderate inhibition of mutagenicity of IQ. However,
the potential antimutagenicity of these plant extracts towards B[a]P was weaker
than that towards IQ. For a direct mutagen, 4-nitroquinoline-N-oxide (NQNO),
only the Sol extracts showed strong inhibitory effects in the TA100 system. The
antimutagenic activity of water extracts of Sec was partly reduced by heating at
100 degrees C for 20 min. The heat-stable antimutagens in Sec extracts could be
produced in the plant extract preparation process. Fractions with molecular
weights above 30,000 showed the strongest antimutagenicity and peroxidase
activity in all the fractions of the Sec extracts.

Publication Types:
In Vitro
Research Support, Non-U.S. Gov't

PMID: 11527563 [PubMed - indexed for MEDLINE]

82: Indian J Exp Biol. 2001 Feb;39(2):137-42.

Effect of Centella asiatica Linn on physical and chemical factors induced
gastric ulceration and secretion in rats.

Sairam K, Rao CV, Goel RK.

Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu
University, Varanasi 221005, India.

Centella asiatica is commonly mentioned as a Rasayana in Ayurveda, an ancient
system of Indian medicine for various ailments including abdominal disorders.
Rasayanas have been advocated for use in rejuvenation therapy. The present study
was conducted to evaluate the possible anti-ulcerogenic activity of fresh juice
of C. asiatica (CAJ) against ethanol-, aspirin-, cold-restraint stress- and
pyloric ligation induced gastric ulcers in rats. The drug given orally in doses
of 200 and 600 mg/kg twice daily for five days, showed significant protection
against all the above experimental ulcer models and the results were comparable
with those elicited by sucralfate (SF, 250 mg/kg, p.o., BD x 5 days). CAJ showed
little or no effect on offensive acid-pepsin secretion. However, at 600 mg/kg
CAJ significantly increased gastric juice mucin secretion and increased the
mucosal cell glycoproteins signifying increase in cellular mucus. It also
decreased cell shedding indicating fortification of mucosal barrier. Thus, the
ulcer protective effect of CAJ may be due to strengthening of the mucosal
defensive factors.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11480209 [PubMed - indexed for MEDLINE]

83: Phytomedicine. 2001 May;8(3):230-5.

In vitro keratinocyte antiproliferant effect of Centella asiatica extract and
triterpenoid saponins.

Sampson JH, Raman A, Karlsen G, Navsaria H, Leigh IM.

The Centre for Bioactivity Screening of Natural Products, King's College London,
UK.

Psoriasis is a hyperproliferative skin disorder estimated to be present in 1-3%
of most populations. Conventional therapy using corticosteroids, Vitamin D
analogs and cytotoxic agents eg psoralens is associated with low success rate
and many side effects. Traditional plant remedies may provide leads for new
treatments. A rapid-throughput, in vitro bioassay has been utilised to examine
plants for inhibitory effects on the growth of SVK-14 keratinocytes. Centella
asiatica, a reputed anti-psoriatic herb, has been compared against the
psoralen-containing seeds of Psoralea corylifolia and the synthetic
anti-psoriatic agent dithranol (anthralin). Aqueous extracts of Psoralea
corylifolia and Centella asiatica inhibited keratinocyte replication with IC50
values of 18.4 +/- 0.6 microg/ml and 209.9 +/- 9.8 mg/ml respectively prior to
treatment with polyvinylpolypyrrolidone (PVPP) and 36.3 +/- 3.3 mg/ml and 238.0
+/- 2.5 mg/ml respectively after PVPP treatment of the extracts. The effect
produced by C. asiatica is thus unlikely to be due to phenolic compounds. It
may, however, be due to its two constituent triterpenoid glycosides
madecassoside and asiaticoside which had IC50 values of 8.6 +/- 0.6 microM
respectively. These values were comparable to their concentrations in the crude
extract and to the IC50 of dithranol (5.1 +/- 0.4 microM). These results suggest
that the potential use of C. asiatica extracts as a topical anti-psoriatic agent
is worthy of further investigation.

Publication Types:
Comparative Study

PMID: 11417919 [PubMed - indexed for MEDLINE]

84: Physiol Behav. 2001 May;73(1-2):19-23.

Protection against radiation-induced conditioned taste aversion by Centella
asiatica.

Shobi V, Goel HC.

Radiation Biology Division, Institute of Nuclear Medicine and Allied Sciences,
DRDO, Lucknow Marg, New Delhi 110 054, India.

Radiations are known to cause behavioural perturbations like conditioned taste
aversion (CTA), performance decrement, learning, etc., even at very low doses.
The manifestation of radiation-induced behavioural degradation has not been
understood well and requires further studies. Therefore, the effects of low-dose
whole-body 60Co gamma-irradiation in male rats were studied in terms of body
weight and CTA learning. For CTA, the consumption of saccharin solution was
considered as a parameter. To protect against the adverse effects of radiation,
Centella asiatica (aqueous extract) was tested and compared with ondansetron, a
standard antiemetic drug. A dose of 2 Gy incurred significant body weight loss
[t(9)=9.00, P<.05] and induced CTA in rats [t(26)=9.344, P<.01]. Administration
of C. asiatica (100 mg/kg bw ip, 2 Gy, -1 h) rendered significant
radioprotection against radiation-induced body weight loss and CTA that became
evident on the second postirradiation day [t(7)=0.917, P>>.05; t(7)=4.016,
P>.05]. Ondansetron (1 mg/kg bw) elicited higher degree of protection against
CTA [t(7)=3.641, P>.05] than C. asiatica [t(7)=7.196, P>.05] on the first
postirradiation day, but on the second postirradiation day, both were equally
effective [t(7)=3.38, P>.05; t(7)=4.01, P>.05]. In case of C. asiatica-treated
animals, however, there was a consistently declining CTA from the second to the
fifth postirradiation day whereas in ondansetron-treated animals it was
inconsistent. Present investigation suggests that C. asiatica could be useful in
preventing radiation-induced behavioural changes during clinical radiotherapy.

PMID: 11399290 [PubMed - indexed for MEDLINE]

85: Int J Pharm. 2001 Jun 4;220(1-2):141-7.

Development of a novel dosage form for intramuscular injection of titrated
extract of Centella asiatica in a mixed micellar system.

Kim C, Hwang YY, Chang JY, Choi HG, Lim SJ, Lee MK.

College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong,
Kwanak-Ku, 151-742, Seoul, South Korea. [email protected]

Titrated extract of Centella asiatica (TECA), a drug used in treating systemic
scleroderma, is poorly water-soluble. A conventional dosage form for the
intramuscular injection of TECA, propylene glycol (PG)-based TECA solution,
causes severe pain after intramuscular injection. To improve the solubility of
TECA and reduce pain after injection, mixed micellar systems composed of 10%
surfactant mixture (Tween 20 and Tween 85) and 90% phosphate-buffered saline, pH
7.0 (PBS) were prepared. As the ratio of Tween 20 to Tween 85 increased from
0:10 to 10:0, the solubility of TECA in the mixed micellar systems increased
from 7- to 26-fold compared to that in PBS (pH 7.0). The droplet size of
micelles gradually decreased with the increasing ratio of Tween 20 to Tween 85
from 0:10 to 4:6, followed by an abrupt decrease in size above the ratio of 6:4.
Furthermore, the micellar systems prepared with Tween 20 and Tween 85 at the
ratio of 6:4, 8:2 or 10:0 could solubilize TECA more than 10 mg/ml and the
resultant droplet sizes were less than 2 microm. No significant changes were
observed in the droplet sizes and asiaticoside contents in these micellar
formulations during storage, indicating these systems are stable for at least 60
days. Their osmotic pressures were remarkably lower than those of PG-based TECA
solution and similar to that of saline solution, irrespective of dilution
ratios. Most importantly, they markedly reduced the number of writhes compared
with PG-based TECA solution after injection to mice. All of these results
suggest that these three TECA micellar formulations prepared with Tween 20 and
Tween 85 improved the solubility of TECA and reduced pain following injection,
possibly due to the decrease in osmotic pressure. Thus, these micellar
formulations composed of optimum ratios of Tween 20 and Tween 85 may have a
potential as dosage forms for the intramuscular injection of a poorly
water-soluble TECA.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11376976 [PubMed - indexed for MEDLINE]

86: Altern Med Rev. 2001 Apr;6(2):126-40.

Hemorrhoids and varicose veins: a review of treatment options.

MacKay D.

Thorne Research, 4616 SE 30th, Portland, OR 97202, USA. [email protected]

Hemorrhoids and varicose veins are common conditions seen by general
practitioners. Both conditions have several treatment modalities for the
physician to choose from. Varicose veins are treated with mechanical compression
stockings. There are several over-the-counter topical agents available for
hemorrhoids. Conservative therapies for both conditions include diet, lifestyle
changes, and hydrotherapy which require a high degree of patient compliance to
be effective. When conservative hemorrhoid therapy is ineffective, many
physicians may choose other non-surgical modalities: injection sclerotherapy,
cryotherapy, manual dilation of the anus, infrared photocoagulation, bipolar
diathermy, direct current electrocoagulation, or rubber band ligation. Injection
sclerotherapy is the non-surgical treatment for primary varicose veins.
Non-surgical modalities require physicians to be specially trained, own
specialized equipment, and assume associated risks. If a non-surgical approach
fails, the patient is often referred to a surgeon. The costly and uncomfortable
nature of treatment options often lead a patient to postpone evaluation until
aggressive intervention is necessary. Oral dietary supplementation is an
attractive addition to the traditional treatment of hemorrhoids and varicose
veins. The loss of vascular integrity is associated with the pathogenesis of
both hemorrhoids and varicose veins. Several botanical extracts have been shown
to improve microcirculation, capillary flow, and vascular tone, and to
strengthen the connective tissue of the perivascular amorphous substrate. Oral
supplementation with Aesculus hippocastanum, Ruscus aculeatus, Centella
asiatica, Hamamelis virginiana, and bioflavonoids may prevent time-consuming,
painful, and expensive complications of varicose veins and hemorrhoids.

Publication Types:
Review

PMID: 11302778 [PubMed - indexed for MEDLINE]

87: Minerva Cardioangiol. 2001 Apr;49(2):159-63.

[Effectiveness of the combination of alpha tocopherol, rutin, melilotus, and
centella asiatica in the treatment of patients with chronic venous
insufficiency]

[Article in Italian]

Cataldi A, Gasbarro V, Viaggi R, Soverini R, Gresta E, Mascoli F.

Unita Operativa Chirurgia Vascolare, Arcispedale S. Anna, Turin, Italy.
[email protected]

BACKGROUND: The aim of this comparative clinical study was to evaluate the
efficacy of the association of alphatocopherol, rutin, melilotus officinalis,
and centella asiatica with oral administration in patients with chronic venous
insufficiency. METHODS: Thirty patients with chronic venous insufficiency have
been randomized in two groups of fifteen subjects (control and treatment group).
During the period of treatment the patients didn't wear elastocompressive
stockings. The therapeutic efficacy and the clinical tolerability of this
association have been valued with clinical-instrumental evaluations and by a
control after 15 and 30 days. Functional bothers, cramps and the edema have been
valued in function presence and of their gravity with a clinical-score between 0
and 4. RESULTS: At the end of the observation period, a significant improvement
of the clinical simptomatology was obtained, characterised by a diminution of
the sovrafascial edema. CONCLUSIONS: The present study confirms previous
clinical experiences regarding the described treatment and suggests its
application in chronic venous insufficiency.

Publication Types:
Clinical Trial
English Abstract
Randomized Controlled Trial

PMID: 11292962 [PubMed - indexed for MEDLINE]

88: J Clin Psychopharmacol. 2000 Dec;20(6):680-4.

A double-blind, placebo-controlled study on the effects of Gotu Kola (Centella
asiatica) on acoustic startle response in healthy subjects.

Bradwejn J, Zhou Y, Koszycki D, Shlik J.

Royal Ottawa Hospital and the Department of Psychiatry, University of Ottawa,
Ontario, Canada. [email protected]

Investigations of the pharmacologic profile of medicinal plants have revealed
that a number of plants with purported anxiolytic activity bind to
cholecystokinin (CCK) receptors. This finding is intriguing in view of the
proposed involvement of CCK in the pathophysiology of fear and anxiety. This
double-blind, placebo-controlled study was undertaken to evaluate the anxiolytic
activity of Gotu Kola (Centella asiatica) in healthy subjects. Gotu Kola has
been used for centuries in Ayurvedic and traditional Chinese medicine to
alleviate symptoms of depression and anxiety. Recent studies in the rat have
shown that long-term pretreatment with Gotu Kola decreases locomotor activity,
enhances elevated-plus maze performance, and attenuates the acoustic startle
response (ASR). In this study, the authors evaluated the effects of Gotu Kola on
the ASR in humans. Subjects were randomly assigned to receive either a single
12-g orally administered dose of Gotu Kola (N = 20) or placebo (N = 20). The
results revealed that compared with placebo, Gotu Kola significantly attenuated
the peak ASR amplitude 30 and 60 minutes after treatment. Gotu Kola had no
significant effect on self-rated mood, heart rate, or blood pressure. These
preliminary findings suggest that Gotu Kola has anxiolytic activity in humans as
revealed by the ASR. It remains to be seen whether this herb has therapeutic
efficacy in the treatment of anxiety syndromes.

Publication Types:
Clinical Trial
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

PMID: 11106141 [PubMed - indexed for MEDLINE]

89: Life Sci. 2000 Oct 13;67(21):2647-53.

Effects of Centella asiatica on ethanol induced gastric mucosal lesions in rats.

Cheng CL, Koo MW.

Department of Pharmacology, Faculty of Medicine, The University of Hong Kong,
China.

Centella asiatica is a herbal medicine widely used in China and India for wound
healing. The aim of this study was to examine its effects on the prevention of
ethanol induced gastric lesions in rats. Gastric transmucosal potential
difference (PD) was reduced by the application of 50% ethanol in the gastric
ex-vivo chamber model and Centella extract (CE) accelerated its recovery. Oral
administration of CE (0.05 g/kg, 0.25 g/kg and 0.50 g/kg) before ethanol
administration significantly inhibited gastric lesions formation (58% to 82%
reduction) and decreased mucosal myeloperoxidase (MPO) activity in a dose
dependent manner. These results suggested that CE prevented ethanol induced
gastric mucosal lesions by strengthening the mucosal barrier and reducing the
damaging effects of free radicals.

Publication Types:
In Vitro
Research Support, Non-U.S. Gov't

PMID: 11104366 [PubMed - indexed for MEDLINE]

90: Phytomedicine. 2000 Oct;7(5):427-48.

Chemical, pharmacological and clinical profile of the East Asian medical plant
Centella asiatica.

Brinkhaus B, Lindner M, Schuppan D, Hahn EG.

Department of Traditional and Complementary Medicine, Medical Department I,
Friedrich-Alexander University, Erlangen-Nuremberg, Germany.
[email protected]

Centella asiatica is a medicinal plant that has been in use since prehistoric
times. Its active constituents include pentacyclic triterpene derivatives.
Studies have been conducted in particular to investigate the madecassosides and
asiaticosides. In common with most traditional phytotherapeutic agents, Centella
asiatica is used in folk medicine to treat a wide range of indications. In
contrast to other medicinal plants, however, Centella asiatica has been
subjected to quite extensive experimental and clinical investigations. Studies
done in accordance with standardized scientific criteria have shown it to have a
positive effect in the treatment of venous insufficiency and striae gravidarum.
Centella asiatica also appears to be effective in the treatment of wound healing
disturbances. At the present time, clinical studies aimed at investigating the
sedative, analgesic, antidepressive, antimicrobial, antiviral and
immunomodulatory effects that have been demonstrated experimentally, are still
lacking. However, the therapeutic potential of this plant in terms of its
efficacy and versatility is such that further detailed research would appear
worthwhile.

Publication Types:
Review

PMID: 11081995 [PubMed - indexed for MEDLINE]

91: J Pharm Biomed Anal. 2000 Aug 1;23(1):61-8.

Electrospray characterization of selected medicinal plant extracts.

Mauri P, Pietta P.

Istituto Tecnologie Biomediche Avanzate/CNR, Milan, Italy. [email protected]

Extracts of selected medicinal plants were examined by electrospray mass
spectrometry (ESI-MS). This technique allowed identification of the main
components of each extract, thereby providing a typical finger-print of the
examined plants. More specifically, anthocyanins (Vaccinium myrtillus),
isoflavones (Glycine max, soybean), flavonol-glycosides and terpenes (Ginkgo
biloba), triterpenes (Centella asiatica), caffeoyl-quinic acids (Cynara
scolymus, artichoke), ginsenosides (Panax ginseng), catechins (Camellia
sinensis, green tea) and flavones and flavanones (Propolis) were detected
rapidly at levels in the range of 0.1-1 microg/ml, using 0.2-1 mg/ml of each
medicinal plant extract.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10898155 [PubMed - indexed for MEDLINE]

92: Aesthetic Plast Surg. 2000 May-Jun;24(3):227-34.

New innovations in scar management.

Widgerow AD, Chait LA, Stals R, Stals PJ.

As current aesthetic surgical techniques become more standardized and results
more predictable, a fine scar may be the demarcating line between acceptable and
unacceptable aesthetic results. With this in mind, a scar management program has
been adopted based on the modalities of wound support, hydration, and hastened
maturity, all factors gleaned from scientific evidence published over the past
25 years. Tension on a scar in one axis will result in a stretched scar,
probably initiated by neutrophils and their neutral proteases [18,26]. Tension
on a scar from many directions or intermittently will result in a hypertrophic
scar, possibly initiated by lymphocytes but definitely related to a prolongation
of the inflammatory process, with increased fibroblast activity and overabundant
extracellular matrix secretion [24,26]. The common initiating factor is the
tension on the scar, and the critical element needed to counteract this tension
is scar support. Clinical experience has shown us that the most reliable way to
support a scar is by using microporous tape. Hydration is a second beneficial
influence on scar control and is the basis of the use of silicone sheeting and
gel [7,29,36]. Alpha Centella cream has two main components. The first is an
extract from the plant Bulbine frutescens. This increases hydration under the
tape by leaving a layer of fatty vesicles of glycoprotein on the skin surface.
This also has antibacterial properties. The second component is the principal
terpenoids extracted from the Centella asiatica plant. These include asiatic
acid, madecassic acid, and asiaticoside. Centella asiatica has been documented
to aid wound healing in a large number of scientific reports
[5,12,21,22,33,34,40]. The most beneficial effect appears to be the stimulation
of maturation of the scar by the production of type I collagen [4,19] and the
resulting decrease in the inflammatory reaction and myofibroblast production.
Thus these components have been incorporated into the formulation of a scar
management program. This publication reviews much of the available literature
relating to scar management and describes the formulation and use of a scar
management program based on this information.

PMID: 10890953 [PubMed - indexed for MEDLINE]

93: Cochrane Database Syst Rev. 2000;(2):CD000066.

Creams for preventing stretch marks in pregnancy.

Young GL, Jewell D.

Barn Croft Surgery, Temple Sowerby, Penrith, Cumbria, CA10 1RZ.
[email protected]

BACKGROUND: Many women develop stretch marks (striae gravidarum) during
pregnancy. A number of creams have been used to remove these stretch marks.
OBJECTIVES: The objective of this review was to assess the effects of topical
treatments to prevent the development of stretch marks. SEARCH STRATEGY: We
searched the Cochrane Pregnancy and Childbirth Group trials register. In
addition, the Cochrane Controlled Trials Register (CENTRAL/CCTR) was searched.
Date of last search: April 1999. SELECTION CRITERIA: Randomised trials comparing
active creams with placebo for the treatment of stretch marks in pregnant women.
DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted
independently by two reviewers. MAIN RESULTS: One study involving 100 women was
included. Compared to placebo, treatment with a cream containing Centella
asiatica extract, alpha tocopherol and collagen-elastin hydrolysates was
associated with less women developing stretch marks (odds ratio 0.41, 95%
confidence interval 0.17 to 0.99). REVIEWER'S CONCLUSIONS: One particular cream
appears to help prevent the development of stretch marks in pregnancy, but only
for women who had previously suffered stretch marks in pregnancy. There is no
evidence of benefit for general use.

Publication Types:
Review

PMID: 10796111 [PubMed - indexed for MEDLINE]

94: Phytomedicine. 2000 Jan;6(6):411-9.

Anti-herpes simplex virus activities of crude water extracts of Thai medicinal
plants.

Yoosook C, Bunyapraphatsara N, Boonyakiat Y, Kantasuk C.

Department of Microbiology, Faculty of Science, Mahidol University, Bangkok,
Thailand. [email protected]

A number of Thai medicinal plants, recommended as remedies for herpesvirus
infection and have been used in primary health care were investigated for their
intracellular activities against herpes simplex viruses (HSV). Centella asiatica
L., Maclura cochinchinensis Cornor, and Mangifera indica L. contained both
anti-HSV-1 and -2 activities, as determined by plaque inhibition assay. An
inhibition of the production of infectious HSV-2 virions from infected Vero
cells could also be demonstrated. Combinations of each of these reconstituted
extracts with 9-(2-hydroxyethoxymethyl) guanosine (acyclovir; ACV) resulted
either in subadditive, additive, or synergistic interaction, against HSV-2,
depending on the dose of ACV used; mixture of C. asiatica and M. indica exerted
an additive effect in a similar assay. Furthermore, the inhibitory effects of
these plant extracts were also substantiated by flow cytometric analysis of
virus-specific antigens in the infected cells. The active constituent present in
C. asiatica extract was determined to be asiaticoside while in M. indica was
mangiferin. Thus, these data suggest therapeutic potential of these plant
extracts.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10715843 [PubMed - indexed for MEDLINE]

95: Eur J Dermatol. 1999 Jun;9(4):289-96.

Triterpenes from Centella asiatica stimulate extracellular matrix accumulation
in rat experimental wounds.

Maquart FX, Chastang F, Simeon A, Birembaut P, Gillery P, Wegrowski Y.

Laboratory of Biochemistry, UPRESA CNRS 6021, IFR-53 Biomolecules, Faculty of
Medicine, Reims, France. [email protected]

Titrated Extract from Centella asiatica (TECA) is a drug which has been used for
many years in Europe for the treatment of wound healing defects. It is a
reconstituted mixture of 3 triterpenes extracted from the plant, asiatic acid,
madecassic acid and asiaticoside. In this report, we studied the effects of TECA
and its separated components in the wound chamber model described by Schilling
et al. Stainless steel wound chambers were surgically inserted under the skin of
rats and received serial injections of either TECA or its purified components.
Chambers were collected at days 7, 14, 21 or 28 for biochemical analysis or
histological examination. TECA-injected wound chambers were characterized by
increased dry weight, DNA, total protein, collagen and uronic acid contents.
Peptidic hydroproline was also increased, showing an increased remodeling of the
collagen matrix in the wound. The 3 purified components of TECA were all able to
reproduce the effects of the complete drug, with some differences depending on
the product. Asiatic acid and asiaticoside were the most active of the 3
triterpenes. Asiaticoside exerted a preferential stimulation of collagen
synthesis and was active at low doses only. In addition to collagen, the 3
components were also able to stimulate glycosaminoglycan synthesis.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10356407 [PubMed - indexed for MEDLINE]

96: Biol Pharm Bull. 1999 Jul;22(7):703-6.

The effect of tetrandrine and extracts of Centella asiatica on acute radiation
dermatitis in rats.

Chen YJ, Dai YS, Chen BF, Chang A, Chen HC, Lin YC, Chang KH, Lai YL, Chung CH,
Lai YJ.

Department of Radiation Oncology, Mackay Memorial Hospital, Taiwan, Republic of
China.

Radiation injury to the skin is one of the major limiting factors in
radiotherapy. We designed this study using Sprague-Dawley rats to evaluate the
reduction in skin injury achieved using natural products from plant extracts as
protection. The acute skin reaction in tetrandrine- and Madecassol-treated
animals appeared earlier, but was significantly less severe, than in the control
group. The peak skin reactions in the tetrandrine group were less serious than
those of the control group at three different radiation doses. At a high dose
irradiation, the healing effect of tetrandrine is better than Madecassol and
vaseline. The histologic findings indicate that tetrandrine and Madecassol are
able to reduce acute radiation reactions by their anti-inflammatory activity.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10443466 [PubMed - indexed for MEDLINE]

97: J Ethnopharmacol. 1999 Apr;65(1):1-11.

In vitro and in vivo wound healing activity of asiaticoside isolated from
Centella asiatica.

Shukla A, Rasik AM, Jain GK, Shankar R, Kulshrestha DK, Dhawan BN.

Pharmacology Division, Central Drug Research Institute, Lucknow, India.
[email protected]

The activity of asiaticoside, isolated from Centella asiatica, has been studied
in normal as well as delayed-type wound healing. In guinea pig punch wounds
topical applications of 0.2% solution of asiaticoside produced 56% increase in
hydroxyproline, 57% increase in tensile strength, increased collagen content and
better epithelisation. In streptozotocin diabetic rats, where healing is
delayed, topical application of 0.4% solution of asiaticoside over punch wounds
increased hydroxyproline content, tensile strength, collagen content and
epithelisation thereby facilitating the healing. Asiaticoside was active by the
oral route also at 1 mg/kg dose in the guinea pig punch wound model. It promoted
angiogenesis in the chick chorioallantoic membrane model at 40 microg/disk
concentration. These results indicate that asiaticoside exhibits significant
wound healing activity in normal as well as delayed healing models and is the
main active constituent of Centella asiatica.

Publication Types:
In Vitro
Research Support, Non-U.S. Gov't

PMID: 10350364 [PubMed - indexed for MEDLINE]

98: Phytother Res. 1999 Feb;13(1):50-4.

Asiaticoside-induced elevation of antioxidant levels in healing wounds.

Shukla A, Rasik AM, Dhawan BN.

Pharmacology Department, Central Drug Research Institute, Lucknow, India.
[email protected]

Asiaticoside derived from the plant Centella asiatica is known to possess good
wound healing activity. Enhanced healing activity has been attributed to
increased collagen formation and angiogenesis. Since antioxidants have been
reported to play a significant role in the wound healing process we studied the
effect of asiaticoside on the levels of certain antioxidants in the wound so as
to explore the possible involvement of such a mechanism in the asiaticoside
induced wound healing. Asiaticoside application (0.2%, topical) twice daily for
7 days to excision-type cutaneous wounds in rats led to increased enzymatic and
non-enzymatic antioxidants, namely superoxide dismutase (35%), catalase (67%),
glutathione peroxidase (49%), vitamin E (77%) and ascorbic acid (36%) in newly
formed tissues. It also resulted in a several fold decrease in lipid peroxide
levels (69%) as measured in terms of thiobarbituric acid reactive substance.
However, continued application for 14 days showed no significant difference in
these antioxidants compared with their values in vehicle treated wound tissue.
It appears from the present study that asiaticosides enhanced induction of
antioxidant levels at an initial stage of healing which may be an important
contributory factor in the healing properties of this substance.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10189951 [PubMed - indexed for MEDLINE]

99: J Chromatogr Sci. 1999 Feb;37(2):51-5.

Extraction and analysis of cosmetic active ingredients from an anti-cellulitis
transdermal delivery system by high-performance liquid chromatography.

Morganti P, Fionda A, Elia U, Tiberi L.

Mavi Sud, Research & Development Laboratories, Aprilia, Italy.

A new transdermal delivery system that controls cellulitis is evaluated using
reversed-phase high-performance liquid chromatography coupled with photodiode
array detection. An extraction procedure and the validation of the analytical
method to assay the active excipients from the Centella asiatica plant
(asiaticoside, madacessic acid, and asiatic acid) are described. Excellent
results ae obtained in terms of linearity, accuracy, and specificity of the
analytical method.

PMID: 10065405 [PubMed - indexed for MEDLINE]

100: Indian J Exp Biol. 1998 Jun;36(6):569-72.

Evaluation of topical formulations of aqueous extract of Centella asiatica on
open wounds in rats.

Sunilkumar, Parameshwaraiah S, Shivakumar HG.

J.S.S. College of Pharmacy, Mysore, India.

Formulations (ointment, cream and gel) of aqueous extract of C. asiatica, when
applied topically, thrice daily for 24 days on the open wounds in rats increased
cellular proliferation and collagen synthesis at the wound site, as evidenced by
increase in collagen content and tensile strength. The treated wounds
epithelialised faster and the rate of wound contraction was higher as compared
to control wounds. The process of healing was better with gel formulation when
compared to other two formulations.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9731470 [PubMed - indexed for MEDLINE]

101: Hindustan Antibiot Bull. 1997 Feb-Nov;39(1-4):56-60.

In vitro evaluation of inhibitory nature of extracts of 18-plant species of
Chhindwara against 3-keratinophilic fungi.

Qureshi S, Rai MK, Agrawal SC.

Department of Botany, Danielson College, Chhindwara, India.

Effect of extract of 18 plant species, viz., Acorus calamus, Adhatoda vasica,
Amomum subulatum, Andrographis paniculata, Boerhaavia diffusa, Cassia
occidentalis, Centella asiatica, Cymbopogon citratus, Hemidesmus indicus, Hyptis
suaveolens, Malvestrum sp., Passiflora edulis, Pergularia daemia, Peristrophe
bicalyculata, Shuteria hirsuta, Solanum nigrum, Tecoma stans, and Verbascum
chinense on the growth of Microsporum gypseum, Chrysosporium tropicum and
Trichophyton terrestre was evaluated and discussed. The sensitivity of the
keratinophilic fungi was evaluated by dry-weight method. The maximum inhibition
of mycelial growth was shown by M. gypseum (86.62%) followed by T. terrestre
(81.86%) and C. tropicum (74.06%) when treated with S. hirsuta whereas the
minimum inhibition was exhibited by M. gypseum (0.29%), C. tropicum (0.16%) and
T. terrestre (1.76%) when tested with the extract of P. edulis, A. vasica and B.
diffusa respectively.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10386016 [PubMed - indexed for MEDLINE]

102: Indian J Exp Biol. 1996 Dec;34(12):1208-11.

Effects of Centella asiatica extract on dermal wound healing in rats.

Suguna L, Sivakumar P, Chandrakasan G.

Department of Biochemistry, Central Leather Research Institute Madras, India.

Effects of oral and topical administration of an alcoholic extract of C.
asiatica on rat dermal wound healing was studied. The extract increased cellular
proliferation and collagen synthesis at the wound site, as evidenced by increase
in DNA, protein and collagen content of granulation tissues. Quicker and better
maturation and crosslinking of collagen was observed in the extract-treated
rats, as indicated by the high stability of acid-soluble collagen and increase
in aldehyde content and tensile strength. The extract treated wounds were found
to epithelialise faster and the rate of wound contraction was higher, as
compared to control wounds. The results show that C. asiatica produced different
actions on the various phases of wound repair.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9246912 [PubMed - indexed for MEDLINE]

103: Allergol Immunopathol (Madr). 1996 May-Jun;24(3):132-4.

Allergic contact dermatitis due to Centella asiatica: a new case.

Gonzalo Garijo MA, Revenga Arranz F, Bobadilla Gonzalez P.

Allergology Departament, Infanta Cristina University Hospital, Badajoz Spain.

We report a new case of allergic contact dermatitis due to Centella asiatica, a
weak sensitizer. Patch tests with Centella asiatica at different vehicles and in
different concentrations were carried out. Regarding our results, we suggest as
a routine procedure to start with 1% pet, and when the test remains negative 10%
pet and 2% eth 70 degrees could be used.

Publication Types:
Case Reports

PMID: 8766746 [PubMed - indexed for MEDLINE]

104: Contact Dermatitis. 1995 Dec;33(6):435-6.

Allergic contact dermatitis from butoxyethyl nicotinic acid and Centella
asiatica extract.

Bilbao I, Aguirre A, Zabala R, Gonzalez R, Raton J, Diaz Perez JL.

Servicio de Dermatologia, Hospital de Cruces, Vizcaya, Spain.

Publication Types:
Case Reports

PMID: 8706410 [PubMed - indexed for MEDLINE]

105: J Ethnopharmacol. 1995 Aug 11;48(1):53-7.

Cytotoxic and anti-tumour properties of certain taxa of Umbelliferae with
special reference to Centella asiatica (L.) Urban.

Babu TD, Kuttan G, Padikkala J.

Amala Cancer Research Centre, Kerala, India.

Centella asiatica (L.) Urban (Umbelliferae) is commonly used in the Ayurvedic
system of medicine to treat various diseases. The present study examines the
anti-tumour effect of the crude extract (CE) of Centella asiatica as well as its
partially purified fractions (AF) from chromatographic procedures by both in
vitro short and long term chemosensitivity and in vivo tumour model test
systems. AF dose dependently inhibited the proliferation of the transformed cell
lines significantly more than did the CE and other solvent fractions. Fifty
percent effective doses on hour 3 exposure to AF were 17 and 22 micrograms/ml
for Ehrlich ascites tumour cells (EAC) and Dalton's lymphoma ascites tumour
cells (DLA), respectively. However, practically no toxic effects were detected
in normal human lymphocytes. AF also significiantly suppressed the
multiplication of mouse lung fibroblast (L-929) cells at a concentration of 8
micrograms/ml in long term culture. Oral administration of the extracts (CE and
AF) retarded the development of solid and ascites tumours and increased the life
span of these tumour bearing mice. Tritiated thymidine, uridine and leucine
incorporation assay suggest that the fraction acts directly on DNA synthesis.

Publication Types:
In Vitro
Research Support, Non-U.S. Gov't

PMID: 8569247 [PubMed - indexed for MEDLINE]

106: Contact Dermatitis. 1994 Sep;31(3):201.

Allergic contact dermatitis due to Centella asiatica extract.

Danese P, Carnevali C, Bertazzoni MG.

Department of Dermatology, C. Poma Hospital, Mantova, Italy.

Publication Types:
Case Reports

PMID: 7821029 [PubMed - indexed for MEDLINE]

107: Pak J Pharm Sci. 1994 Jul;7(2):17-24.

Amino Acid analysis of intellan, a herbal product used in enhancing brain
function.

Ahmad S, Rahman A, Fatima K, Bader Y.

Pharmaceutical & Fine Chemical Research Centre, PCSIR Labs. Karachi.

Analysis of the drug "INTELLAN" and two reputed plants i.e. Centella asiatica
and Herpestis monniera used in the preparation of the drug reveals that glutamic
and aspartic acids are present in high concentration in the drug and are also
required by brain in high concentration to keep itself in higher gears. Both
these amino acids are used as neurotransmitters and also in stabilizing and
stimulating the activities of brain, thus resulting in better performance.

PMID: 16414752 [PubMed - in process]

108: Minerva Cardioangiol. 1994 Jun;42(6):299-304.

[The microcirculatory activity of Centella asiatica in venous insufficiency. A
double-blind study]

[Article in Italian]

Cesarone MR, Laurora G, De Sanctis MT, Incandela L, Grimaldi R, Marelli C,
Belcaro G.

Istituto di Clinica Cardiovascolare, Universita degli Studi G. D'Annunzio,
Chieti.

In 87 patients with chronic venous hypertensive microangiopathy the efficacy of
oral FTTCA (Centella asiatica) administered for 60 days was tested. The
microcirculatory effects of two dosages (30 mg bid and 60 mg bid) versus placebo
was assessed in a double blind study. The compound was well tolerated and no
unwanted effects were observed. Microcirculatory parameters--peri-malleolar skin
flux at rest (RF) and transcutaneous PO2 and PCO2--improved as did the
abnormally increased RF, PCO2 decreased and PO2 increased in comparison with
values measured at inclusion. These results confirm the efficacy of FTTCA in
venous hypertensive microangiopathy. Furthermore the effects of FTTCA appear to
be dose-related.

Publication Types:
Clinical Trial
Comparative Study
English Abstract
Randomized Controlled Trial

PMID: 7936334 [PubMed - indexed for MEDLINE]

109: Indian J Lepr. 1994 Jan-Mar;66(1):65-8.

In vitro experiments with Centella asiatica: investigation to elucidate the
effect of an indigenously prepared powder of this plant on the acid-fastness and
viability of M. tuberculosis.

Herbert D, Paramasivan CN, Prabhakar R, Swaminathan G.

Tuberculosis Research Center (ICMR), Chetput, Madras.

The herb Centella asiatica (Linn.), found throughout India, is acclaimed to have
medicinal properties and has been used in leprosy patients from very early
times. It is considered that the active compound of this herb, called
asiaticoside, probably acts on the waxy covering of M. leprae. The in vitro
effect of an indigenously produced dry powder of Centella asiatica (CA) on the
acid-fastness and viability of M. tuberculosis was investigated in the present
study. The results indicate that CA may not have any direct action on the
acid-fastness or viability of M.tuberculosis H37Rv in vitro. Further studies
using purified asiaticoside of the plant or in vivo studies are required.

PMID: 7983394 [PubMed - indexed for MEDLINE]

110: Contact Dermatitis. 1993 Oct;29(4):175-9.

Centella asiatica (Indian pennywort), an effective therapeutic but a weak
sensitizer.

Hausen BM.

Department of Dermatology, University Hospital, Hamburg, Germany.

The sensitizing capacity of Centella asiatica (raw extract) and its triterpenic
constituents asiaticoside, asiatic acid and madecassic acid has been studied in
guinea pigs. The extract itself as well as the 3 acids were found to be very
weak sensitizers. Centella asiatica extract is used effectively in the treatment
of keloids, leg ulcers, phlebitis, slow-healing wounds, leprosy, surgical
lesions, striae distensae and cellulitis. Although applied frequently to damaged
skin, the risk of acquiring contact sensitivity to this plant or its
constituents is low.

Publication Types:
Case Reports

PMID: 8281778 [PubMed - indexed for MEDLINE]

111: Cytotechnology. 1993;13(3):221-6.

Enhancement of the attachment on microcarriers and tPA production by fibroblast
cells in a serum-free medium by the addition of the extracts of Centella
asiatica.

Kim YN, Park YS, Kim HK, Jeon BC, Youn SE, Lee HY.

Department of Food Engineering, Kangwon National University, Chunchon, Korea.

The addition of ethanol extracts of Centella asiatica showed a remarkable
enhancement of fibroblast cells attachment to Cytodex beads in serum-free (SF)
medium. It also improves tPA production in both batch and perfusion
cultivations. The optimal concentration for SF medium was determined as 2 ppm of
the extracts when using Cytodex III. In batch cultivation a high specific tPA
production rate was obtained, compared to that from 5% FBS containing medium.
However, a fast specific growth rate was observed in 5% FBS medium. In perfusion
cultivation a reasonably good cell density and tPA production was achieved at a
perfusion rate of 2.4 x 10(6) (viable cell/ml) and 0.65 (micrograms/ml),
respectively at 22 ml/min.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 7764663 [PubMed - indexed for MEDLINE]

112: Indian J Exp Biol. 1992 Oct;30(10):889-91.

Effects of plant extract Centella asiatica (Linn.) on cold restraint stress
ulcer in rats.

Chatterjee TK, Chakraborty A, Pathak M, Sengupta GC.

Department of Pharmaceutical Technology, Jadavpur University, Calcutta, India.

Extract of C. asiatica (Linn.) inhibited significantly gastric ulceration
induced by cold and restraint stress (CRS) in Charles-Foster rats, Antiulcer
activity of plant extract was compared with famotidine (H2-antagonist) and
sodium valproate (anti-epileptic). Plant extract, formotidine and sodium
valproate showed a dose dependent reduction of gastric ulceration. Plant extract
increased brain GABA level which was also dose dependent. Pretreatment with
bicuculline methiodide (specific GABAA-antagonist) at the dose level of 0.5
mg/kg im, reversed the antiulcerogenic activity of both plant extract and sodium
valproate. Bicuculline as such did not induce gastric ulceration in normal rat.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 1293014 [PubMed - indexed for MEDLINE]

113: Minerva Cardioangiol. 1992 Apr;40(4):137-43.

[Activity of Centella asiatica in venous insufficiency]

[Article in Italian]

Cesarone MR, Laurora G, De Sanctis MT, Belcaro G.

Clinica Cardiovascolare, Universita degli Studi G. D'Annunzio, Chieti.

In this a review concerning TTFCA, its effects on metabolism in the connective
tissue of the vascular wall and on the microcirculation are presented and
discussed. This compound is effective in venous insufficiency, reducing ankle
edema, foot swelling, capillary filtration rate and by improving
microcirculatory parameters (RF, VAR PO2-PCO2). TTFCA displays a significant
activity in venous hypertensive microangiopathy and its effects are
dose-dependent.

Publication Types:
Clinical Trial
Comparative Study
English Abstract

PMID: 1528498 [PubMed - indexed for MEDLINE]

114: Contact Dermatitis. 1992 Mar;26(3):192-3.

Allergic contact dermatitis from a cream containing Centella asiatica extract.

Izu R, Aguirre A, Gil N, Diaz-Perez JL.

Dermatology Department, Cruces Hospital, Bilbao, Spain.

Publication Types:
Case Reports

PMID: 1387057 [PubMed - indexed for MEDLINE]

115: Phytochemistry. 1992 Jan;31(1):227-31.

Triterpenoids and their glycosides from the bark of Schefflera octophylla.

Sung TV, Lavaud C, Porzel A, Steglich W, Adam G.

Institute of Natural Products Chemistry, National Research Centre of SRV, Hanoi,
Vietnam.

A new triterpene and its glycosides were isolated from the bark of Schefflera
octophylla together with asiatic acid and asiaticoside. Based on spectroscopic
data, especially 2DNMR, and chemical transformations the structures of the new
compounds were determined as 3 alpha-hydroxy-urs-12-ene-23,28-dioic acid and 3
alpha-hydroxy-urs-12-ene-23,28-dioic acid 28-O-[alpha-L-rhamnopyranosyl
(1----4)-O-beta-D-glucopyranosyl (1----6)]-beta-D-glucopyranoside. For the first
time asiaticoside was isolated from a plant other than Centella asiatica.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 1367880 [PubMed - indexed for MEDLINE]

116: Haematologica. 1991 May-Jun;76(3):256-9.

Centella Asiatica Triterpenic Fraction (CATTF) reduces the number of circulating
endothelial cells in subjects with post phlebitic syndrome.

Montecchio GP, Samaden A, Carbone S, Vigotti M, Siragusa S, Piovella F.

Clinica Medica II, IRCCS Policlinico San Matteo, Pavia, Italy.

Here we report a study performed in order to assess the number of circulating
endothelial cells (EC) in normal subjects and in patients with postphlebitic
syndrome (PPS), and the effect of treatment with Centella Asiatica Triterpenic
Fraction (CATTF), a drug which has been demonstrated to be effective in
promoting wound healing in vivo. EC counts were determined by means of
differential centrifugation and phase contrast microscopy. Patients with PPS
showed an increased number of circulating EC in comparison to normal subjects
(3.8 +/- 1.2 cells versus 1.5 +/- 0.6 per counting chamber). Treatment for three
weeks with CATTF caused a statistically significant reduction of circulating EC
(1.80 +/- 0.6 cells per counting chamber).

Publication Types:
Clinical Trial

PMID: 1743599 [PubMed - indexed for MEDLINE]

117: Angiology. 1990 Jul;41(7):533-40.

Improvement of capillary permeability in patients with venous hypertension after
treatment with TTFCA.

Belcaro GV, Grimaldi R, Guidi G.

Microcirculation Laboratory, G. D'Annunzio University, Chieti, Italy.

The VSC (vacuum suction chamber) device, a new system to evaluate local
capillary permeability, was used with laser Doppler flowmetry to study
variations of permeability and of the microcirculation in 10 normal subjects; in
22 patients with moderate, superficial venous hypertension; and in 12 patients
with postphlebitic limbs and severe venous hypertension. All these patients had
distal (ankle and foot edema) in the evening. After a first assessment these
subjects were studied again after two weeks without treatment and after two
weeks' treatment with total triterpenic fraction of centella asiatica (TTFCA),
tablets, 60 mg, tid. The VSC produces a wheal on the skin of the perimalleolar
region that disappears (in average) in less than sixty minutes in normal
subjects. The disappearance time (DT) is greater in conditions of increased
capillary filtration and permeability. The three groups of subjects (normal and
those with superficial and severe venous hypertension) had significantly
different, increasing disappearance time of the wheals at the first observation.
There were no significant changes after two weeks' observation, but after 2
weeks' treatment with TTFCA, there was a significant decrease of DT both in
limbs with superficial and with deep venous incompetence. The improvement
(decrease) of the abnormally increased capillary permeability was associated
with a significant improvement of the microcirculation and symptoms (studied by
an analogue scale line). In conclusion this study showed a combined improvement
of the microcirculation and capillary permeability after treatment with TTFCA
and the possibility of using the VSC to evaluate the effects of drugs (or other
treatment) on local capillary permeability in patients with venous hypertension.

PMID: 2389834 [PubMed - indexed for MEDLINE]

118: J Ethnopharmacol. 1990 Feb;28(2):235-41.

Pharmacokinetics of the total triterpenic fraction of Centella asiatica after
single and multiple administrations to healthy volunteers. A new assay for
asiatic acid.

Grimaldi R, De Ponti F, D'Angelo L, Caravaggi M, Guidi G, Lecchini S, Frigo GM,
Crema A.

Department of Internal Medicine and Therapeutics, University of Pavia, Italy.

A new HPLC assay method was used to investigate the pharmacokinetics of asiatic
acid after oral administration of the total triterpenic fraction of Centella
asiatica in single doses (30 or 60 mg) and after a 7-day treatment (30 or 60 mg
twice daily). Twelve healthy volunteers received each treatment following a
randomized cross-over design with trials separated by a 3-week interval. The
time of peak plasma concentration was not affected by dosage difference or by
treatment scheme. Differences in peak plasma concentration and area under the
concentration vs. time curve from 0 to 24 h (AUC0-24) calculated after 30 or 60
mg administration (single dose) were accounted for by the different dose
regimen. However, after chronic treatment with both 30 and 60 mg, peak plasma
concentrations, AUC0-24 and half-life were significantly higher than those
observed after the corresponding single dose administration. This phenomenon
could be explained by a metabolic interaction between asiatic acid and
asiaticoside, which is transformed into asiatic acid in vivo.

Publication Types:
Clinical Trial
Comparative Study
Randomized Controlled Trial

PMID: 2329813 [PubMed - indexed for MEDLINE]

119: Connect Tissue Res. 1990;24(2):107-20.

Stimulation of collagen synthesis in fibroblast cultures by a triterpene
extracted from Centella asiatica.

Maquart FX, Bellon G, Gillery P, Wegrowski Y, Borel JP.

Laboratory of Biochemistry, CNRS URA, Faculty of Medicine, Reims, France.

The drug "Titrated Extract from Centella asiatica" (TECA), used for its
stimulating properties on the healing of wounds, is a mixture of 3 terpenes
extracted from a tropical plant: asiatic acid (30%, w/w), madecassic acid (30%,
w/w) and asiaticoside (40%, w/w). The effects of TECA and its individual
components were checked on human foreskin fibroblast monolayer cultures. TECA
increased the collagen synthesis in a dose-dependent fashion whereas a
simultaneous decrease in the specific activity of neosynthesized collagen was
observed. Asiatic acid was found to be the only component responsible for
collagen synthesis stimulation. TECA and all three terpenes increased the
intracellular free proline pool. This effect was independent of the stimulation
of collagen synthesis.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 2354631 [PubMed - indexed for MEDLINE]

120: Angiology. 1990 Jan;41(1):12-8.

Capillary filtration and ankle edema in patients with venous hypertension
treated with TTFCA.

Belcaro GV, Rulo A, Grimaldi R.

Cardiovascular Clinic, University G. D'Annunzio, Chieti, Italy.

The variation of capillary filtration rate (CFR), ankle circumference (AC), and
ankle edema (AE) was evaluated in three groups of patients with venous
hypertension (ambulatory venous pressure greater than 42 mmHg) and in a group of
normal subjects before and after treatment for four weeks with Total Triterpenic
fraction of Centella Asiatica (TTFCA), a venoactive drug acting on the
microcirculation and on capillary permeability. Group A (20 patients) was
treated with TTFCA 60 mg tid; Group B (20 patients) was treated with 30 mg tid;
Group C (12 patients) was treated with placebo; and Group D (10 normal subjects)
was treated with TTFCA 60 mg tid in an open study. Capillary filtration rate was
assessed by venous occlusion plethysmography, ankle edema by a new system called
AECT (Ankle edema coin tester). Subjective symptoms of venous hypertension were
assessed by an analogue scale line considering four symptoms: swelling
sensation, restless lower extremity, pain and cramps, and tiredness. CFR, AC,
and AE were significantly higher in patients in comparison with normal subjects.
After four weeks of TTFCA treatment there was a significant decrease of the
abnormally increased CFR, AC, and AECT time in patients. This was also greater
in the higher dose group. No significant change was observed in the placebo
group and in normal subjects treated with TTFCA. Symptoms were also
significantly improved in the two groups treated with the active drug according
to the dose. No significant changes were observed in the placebo group.(ABSTRACT
TRUNCATED AT 250 WORDS)

Publication Types:
Clinical Trial
Comparative Study
Controlled Clinical Trial

PMID: 2305995 [PubMed - indexed for MEDLINE]

121: Int J Clin Pharmacol Res. 1990;10(4):229-33.

Effects of Centella asiatica extract on mucopolysaccharide metabolism in
subjects with varicose veins.

Arpaia MR, Ferrone R, Amitrano M, Nappo C, Leonardo G, del Guercio R.

Institute of General Medicine and Clinical Methodology, Department and Service
of Medical Angiology, Faculty of Medicine and Surgery, University of Naples,
Italy.

The effects were studied of the total triterpenic fraction of Centella asiatica
on serum levels of the uronic acids and lysosomal enzymes involved in
mucopolysaccharide metabolism (beta-glycuronidase, beta-N-acetylglucosaminidase,
arylsulfatase) in patients with varicose veins. The basal levels of uronic acids
(467.7 +/- 69.3 micrograms/ml) and of lysosomal enzymes (beta-glycuronidase 1.8
+/- 0.4 microM/min/l, beta-N-acetylglucosaminidase 23.1 +/- 0.4 microM/min/l,
arysulfatase 0.078 +/- 0.003 microM/min/l) were elevated, indicating an
increased mucopolysaccharide turnover in subjects with varicose veins. During
treatment with Centella asiatica extract (60 mg/day for three months), these
levels fell progressively. At the end of treatment the serum uronic acid (231.8
+/- 51.5 micrograms/ml), beta-glycuronidase (1.2 +/- 0.05 microM/min/l),
beta-N-acetylglucosaminidase (17.7 +/- 0.7 microM/min/l) and arysulfatase (0.042
+/- 0.003 microM/min/l) levels were highly significantly lower than the basal
levels (p less than 0.01). The results of this trial provide an indirect
confirmation of regulatory effects of the extract of Centella asiatica on
metabolism in the connective tissue of the vascular wall.

PMID: 2150405 [PubMed - indexed for MEDLINE]

122: J Tradit Chin Med. 1989 Jun;9(2):113-6.

An experimental study of the anti-HSV-II action of 500 herbal drugs.

Zheng MS.

Experimental assessments were made on the anti-HSV-II action of 500 herbs by
determinations of the virus inhibition logarithm (VIL). 13 highly effective
herbs (VIL greater than or equal to 4.00) were screened cut, providing a
rational basis for clinical therapy. Among these effective herbs, 10 were
aqueous extracts of Artemisia anomala, Centella asiatica, Epimedium Sagittatum,
Hibiscus mutabilis, Hosta plantaginea, Hypericum japonicum, Inula japonica,
Mosla punctata, Rhododendron simsii, and Rhus chinenses, while 3 were alcohol
extracts of Epimedium Sagittatum, Hypericum japonicum, and Mosla punctata.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 2550706 [PubMed - indexed for MEDLINE]

123: Phlebologie. 1988 Apr-Jun;41(2):359-69.

[Medical and surgical therapies. Their respective indications in lymphedema]

[Article in French]

Coget J.

The treatment of lymphedema, medical or surgical, remains a difficult one. Often
seen at an advanced stage of the disease, the medical treatment can only
stabilize the lesions. Among them, the coumarins, rutins, Centella asiatica
extracts, procyanoside oligomers are the most prescribed. But prophylaxis of
superimposed infections by antibiotics should not be omitted. As for diuretics,
they must be prohibited. Hygienic and dietetic measures should be recommended.
As for surgical treatments, they are numerous and rarely applied, whether it
consists of the tacking technique or Degni's lymphovenous anastomosis. The
latter may be considered in case of high lymphatic obstruction, especially at
the inguinal level. Servelle's lymphangiectomy, very traumatic, is only
exceptionally indicated.

Publication Types:
English Abstract

PMID: 3406093 [PubMed - indexed for MEDLINE]

124: Ital J Biochem. 1988 Mar-Apr;37(2):69-77.

Effect of the triterpenoid fraction of Centella asiatica on macromolecules of
the connective matrix in human skin fibroblast cultures.

Tenni R, Zanaboni G, De Agostini MP, Rossi A, Bendotti C, Cetta G.

Dipartimento di Biochimica, Universita di Pavia.

The mechanism of action of the total triterpenoid fraction extracted from
Centella Asiatica (TTFCA) was evaluated using human skin fibroblasts cultures as
the experimental system. In particular its influence on the biosynthesis of
collagen, fibronectin and proteoglycans was considered. The presence of TTFCA
(25 micrograms/ml) does not seem to affect cell proliferation, total protein
synthesis or the biosynthesis of proteoglycans in a significant way. A
statistically important increase was observed in the percentage of collagen and,
as revealed by immunofluorescence measurements, in cell layer fibronectin. This
effect on collagen and fibronectin may help to explain the action of TTFCA in
promoting wound healing, and suggests an interesting working hypothesis for its
action on basal endothelia.

PMID: 3042688 [PubMed - indexed for MEDLINE]

125: Angiology. 1987 Jan;38(1 Pt 1):46-50.

Titrated extract of Centella asiatica (TECA) in the treatment of venous
insufficiency of the lower limbs.

Pointel JP, Boccalon H, Cloarec M, Ledevehat C, Joubert M.

Ninety-four patients suffering from venous insufficiency of the lower limbs
participated in a multicenter, double-blind versus placebo study. After
randomization, they were allotted for a treatment period of two months to one of
three groups: TECA 120 mg/day, TECA 60 mg/day, or placebo. A significant
difference (p less than 0.05) in favor of TECA was shown for the symptoms of
heaviness in the lower limbs and edema, as well as for the overall evaluation by
the patient. The venous distensibility measured by a mercury strain gauge
plethysmograph at three occlusion pressures was improved for the TECA groups but
aggravated for the placebo group.

Publication Types:
Clinical Trial
Comparative Study
Randomized Controlled Trial

PMID: 3544968 [PubMed - indexed for MEDLINE]

126: Contact Dermatitis. 1985 Nov;13(5):310-3.

Contact dermatitis due to madecassol.

Eun HC, Lee AY.

Madecassol is an extract of Centella asiatica, a member of the Umbelliferae
family. It contains madecassic acid, asiatic acid and asiaticoside. It has been
used as a wound healing agent and for the prevention of cicatrization. We report
contact dermatitis due to Madecassol and a control study with its individual
ingredients.

Publication Types:
Case Reports

PMID: 2936544 [PubMed - indexed for MEDLINE]

127: Farmaco [Prat]. 1984 Oct;39(10):355-64.

[Effect of Centella asiatica on the biosynthetic activity of fibroblasts in
culture]

[Article in Italian]

Del Vecchio A, Senni I, Cossu G, Molinaro M.

Publication Types:
English Abstract

PMID: 6510515 [PubMed - indexed for MEDLINE]

128: Clin Ter. 1984 Sep 30;110(6):555-9.

[Comparative capillaroscopic study of certain bioflavonoids and total
triterpenic fractions of Centella asiatica in venous insufficiency]

[Article in Italian]

Allegra C.

Publication Types:
English Abstract

PMID: 6238770 [PubMed - indexed for MEDLINE]

129: Minerva Cardioangiol. 1982 Apr;30(4):201-7.

[Centella asiatica extract in venous pathology of the lower limbs and its
evaluation as compared with tribenoside]

[Article in Italian]

Marastoni F, Baldo A, Redaelli G, Ghiringhelli L.

Publication Types:
English Abstract

PMID: 6896366 [PubMed - indexed for MEDLINE]

130: Clin Ter. 1981 Dec 15;99(5):507-13.

[Centella asiatica extract in venous disorders of the lower limbs. Comparative
clinico-instrumental studies with a placebo]

[Article in Italian]

Allegra C, Pollari G, Criscuolo A, Bonifacio M, Tabassi D.

Publication Types:
Clinical Trial
Comparative Study
Controlled Clinical Trial
English Abstract

PMID: 7037273 [PubMed - indexed for MEDLINE]

131: Sem Hop. 1979 Nov 8-15;55(37-38):1749-50.

[Use of a titrated extract of Centella asiatica in chronic hepatic disorders
(author's transl)]

[Article in French]

Darnis F, Orcel L, de Saint-Maur PP, Mamou P.

The authors report their preliminary results of a study of the possible
therapeutic activity of a titrated extract of Centella asiatica in chronic
hepatic disorders. Early results are encouraging, especially from a histological
point of view, where improvement in the criteria evaluated was noted in 5 of the
12 patients treated for the longest time. These results have to be assessed in a
critical manner until confirmation is obtained by complementary studies.

Publication Types:
English Abstract

PMID: 230597 [PubMed - indexed for MEDLINE]

132: C R Acad Sci Hebd Seances Acad Sci D. 1978 Mar 13;286(10):789-92.

[Modification of the kinetics of healing after iterative exeresis in the rat.
Action of a triterpenoid and its derivatives on the duration of healing]

[Article in French]

Poizot A, Dumez D.

The authors have studied the action of Titrated Extract of Centella asiatica
(TECA) on the duration off healing of iterative wounds in the Rat. After
repeated exeresis, the planimetric quantification of the wounds, by episcopic
projection, shows that the healing process involves an immediate phase of
dilatation followed by another of contraction. A mathematical analysis has
permitted determination of times of semi-healing and has shown that these are
significantly lengthened after several exeresis in the control group. When
administered by oral route, at a 100 mg/kg dosing, TECA shortens significantly
this lengthening of time, acting more specifically on the immediate process of
healing.

Publication Types:
English Abstract

PMID: 417867 [PubMed - indexed for MEDLINE]

133: Therapie. 1977 Sep-Oct;32(5):573-83.

[Animal study of the transcutaneous movement of the tritium-labelled active
principles of Centella asiatica L. extract after administration in impregnated
gauze or unguent]

[Article in French]

Viala A, Cano JP, Durand A, Paulin R, Roux F, Placidi M, Pinhas H, Lefournier C.

Publication Types:
English Abstract

PMID: 613474 [PubMed - indexed for MEDLINE]

134: Bull Soc Pathol Exot Filiales. 1974 Sep-Oct;67(5):471-8.

[Results of a controlled experiment of the titrated extract of Centella asiatica
in a leper population with perforative foot lesions]

[Article in French]

Nebout M.

Publication Types:
Comparative Study
English Abstract

PMID: 4480467 [PubMed - indexed for MEDLINE]

135: C R Acad Sci Hebd Seances Acad Sci D. 1974 Mar 25;278(13):1743-6.

[Action of a pentacyclic triterpenoid, asiaticoside, isolated from Hydrocotyle
masagascariensis or Centella asiatica, against gastric ulceration in the Wistar
rat exposed to cold at 2 degrees C]

[Article in French]

Ravokatra A, Nigeon-Dureuil M, Ratsimamanga AR.

PMID: 4211283 [PubMed - indexed for MEDLINE]

136: Int Surg. 1973 Jul;58(7):451-2 passim.

Use of titrated extract of Centella asiatica (TECA) in bilharzial bladder
lesions.

Fam A.

PMID: 4717500 [PubMed - indexed for MEDLINE]

137: Lille Med. 1971;17:Suppl 3:574-9.

[Action of the titrated extract of Centella Asiatica in the cicatrization of leg
ulcers (10 mg. tablets). Apropos of 50 cases]

[Article in French]

Huriez C.

PMID: 5153018 [PubMed - indexed for MEDLINE]

138: Indian J Exp Biol. 1968 Jul;6(3):181-2.

Crude extract of Centella asiatica and products derived from its glycosides as
oral antifertility agents.

Dutta T, Basu UP.

PMID: 5718539 [PubMed - indexed for MEDLINE]

139: C R Acad Sci Hebd Seances Acad Sci D. 1967 Jan 9;264(2):407-10.

[Isolation of a new triterpenic acid from Centella asiatica (L.) Urb. of
Madagascar: madecassic acid]

[Article in French]

Boiteau P, Chanez M.

PMID: 4961798 [PubMed - indexed for MEDLINE]

140: Ann Pharm Fr. 1963 Jul-Aug;21:561-7.

[ANTHRONE DETERMINATION OF THE ASIATICOSIDE ISOLATED FROM CENTELLA ASIATICA BY
QUANTITATIVE CHROMATOGRAPHY ON THIN LAYERS OF GLASS POWDER.]

[Article in French]

RAHANDRAHA T, CHANEZ M, BOITEAU P, JAQUARD S.

PMID: 14048142 [PubMed - OLDMEDLINE]

141: Ann Pharm Fr. 1963 Apr;21:313-20.

[Anthrone determination of asiaticoside, ester-oside of Centella asiatica.]

[Article in French]

RAHANDRAHA T, CHANEZ M, BOITEAU P.

PMID: 13990461 [PubMed - indexed for MEDLINE]

142: J Sci Ind Res (C). 1962 Jan;21C:22-6.

Pharmacognostic study of Merremia emarginata Hallier & comparison with Centella
asiatica Linn.

SHAH CS, SUKKAWALA VM, CHAVAN AR.

PMID: 14039163 [PubMed - indexed for MEDLINE]

143: Prensa Med Argent. 1961 Nov 24;48:3154-6.

[Treatment of stubborn ulcers of the lower extremities with Asiaticoside
(Centella asiatica).]

[Article in Spanish]

ANTONELLI NC, SPERA N.

PMID: 13861793 [PubMed - indexed for MEDLINE]

144: Minerva Chir. 1960 Nov 30;15:1235-8.

[On the treatment of cutaneous lesions with extract of "Centella asiatica".]

[Article in Italian]

FINCATO M.

PMID: 13699523 [PubMed - indexed for MEDLINE]

145: Presse Med. 1958 Dec 6;66(86):1933 passim.

[Treatment of leg ulcers by Centella madagascariensis extracts.]

[Article in French]

BOELY C, RATSIMAMANGA AR.

PMID: 13623710 [PubMed - OLDMEDLINE]

146: Lyon Med. 1957 Apr 28;89(17):389-95.

[Asiaticoside; active constituent of Centella asiatica, initiating agent of the
new growth in the early stage of cicatrization of skin ulcers.]

[Article in French]

THIERS H, FAYOLLE J, BOITEAU P, RATSIMAMANGA AR.

PMID: 13440135 [PubMed - indexed for MEDLINE]

147: Therapie. 1956;11(1):125-49.

[Asiaticoside extracted from Centella asiatica and its therapeutic uses in
cicatrization of experimental and refractory wounds (leprosy, cutaneous
tuberculosis and lupus).]

[Article in French]

BOITEAU P, RATSIMAMANGA AR.

PMID: 13337766 [PubMed - indexed for MEDLINE]  

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