1: Arch Biochem Biophys. 2007 Feb 12; [Epub ahead of print]
Molecular cloning and characterization of one member of 3beta/hydroxy sterol
glucosyltransferase gene family in Withania somnifera.
Sharma LK, Madina BR, Chaturvedi P, Sangwan RS, Tuli R.
National Botanical Research Institute, Rana Pratap Marg, Lucknow 226001, Uttar
Pradesh, India.
Sterol glycosides are constituents of plant cell membranes. Glucosylations of
the sterols are catalyzed by sterol glucosyltransferases (SGTs), which are
members of family 1 glycosyltransferases. We have identified the family of SGT
genes expressed in the leaves of a medicinal plant Withania somnifera. One
member (SGTL1) of this gene family was cloned. The full/length cDNA sequence of
SGTL1 represents 2532 bp, comprising untranslated regions (UTRs) of 337 and 89
bp at the 5' and 3' ends, respectively. The amino acid sequence deduced from the
2103 bp open reading frame (ORF) showed homology (67/45%) to the reported plant
SGTs. The presence of two putative transmembrane domains suggested the
association of SGTL1 with membrane. The SGTL1 was expressed in Escherichia coli
and recombinant enzyme from the supernatant was partially purified and
biochemically characterized. The relative activity and kinetic properties of
SGTL1 for different sterols were compared with a recombinant SGT (GenBank
Accession No. ) of Arabidopsis thaliana (AtSGT). Both the recombinant enzymes
showed activity with 3/beta/OH sterols. The distribution of SGTL1 transcript in
W. somnifera, as determined by quantitative PCR, showed higher expression in
roots and mature leaves. Expression of the SGTL1 transcript in the leaves of W.
somnifera was enhanced following the application of salicylic acid. In contrast,
it decreased rapidly on exposure of the plants to heat shock, suggesting
functional role of the enzyme in biotic and abiotic stresses.
PMID: 17324374 [PubMed / as supplied by publisher]
2: Biochim Biophys Acta. 2007 Jan 8; [Epub ahead of print]
Purification and physico/kinetic characterization of 3beta/hydroxy specific
sterol glucosyltransferase from Withania somnifera (L) and its stress response.
Madina BR, Sharma LK, Chaturvedi P, Sangwan RS, Tuli R.
National Botanical Research Institute, Rana Pratap Marg, Lucknow/226001, (U.P.)
India.
Sterol glycosyltransferases catalyze the synthesis of diverse glycosteroids in
plants, leading to a change in their participation in cellular metabolism.
Withania somnifera is a medically important plant, known for a variety of
pharmacologically important withanolides and their glycosides. In this study, a
cytosolic sterol glucosyltransferase was purified 3406 fold to near homogeneity
from W. somnifera leaves and studied for its biochemical and kinetic properties.
The purified enzyme was active with UDP/glucose but not with UDP/galactose as
sugar donor. It exhibited broad sterol specificity by glucosylating a variety of
sterols and phytosterols with 3beta/OH group. It showed a low level of activity
with flavonoids and isoflavonoids. The enzyme gave maximum K(cat)/K(m) value
(0.957) for 24/methylenecholesterol that resembles aglycone structure of
pharmacologically important sitoindosides VII and VIII from W. somnifera. The
enzyme follows ordered sequential bisubstrate mechanism of reaction, in which
UDP/glucose and sterol are the first and second binding substrates. This is the
first detailed kinetic study on purified plant cytosolic sterol
glucosyltransferases. Results on peptide mass fingerprinting and substrate
specificity suggested that the enzyme belongs to the family of secondary
metabolite glucosylating glucosyltransferases. The enzyme activity exhibited a
rapid in vivo response to high temperature and salicylic acid treatment of
plants, suggesting its physiological role in abiotic and biotic stress.
PMID: 17293176 [PubMed / as supplied by publisher]
3: Phytother Res. 2007 Jan 12; [Epub ahead of print]
In Vivo antimalarial activity of aqueous extracts from Kenyan medicinal plants
and their Chloroquine (CQ) potentiation effects against a blood/induced
CQ/resistant rodent parasite in mice.
Muregi FW, Ishih A, Suzuki T, Kino H, Amano T, Mkoji GM, Miyase T, Terada M.
Department of Parasitology, Hamamatsu University School of Medicine, 1/20/1
Handayama, Hamamatsu 431/3192, Japan.
Hot water extracts from eight medicinal plants representing five families, used
for malaria treatment in Kenya were screened for their in vivo antimalarial
activity in mice against a chloroquine (CQ) resistant Plasmodium berghei NK65,
either alone or in combination with CQ. Extracts of three plants, Toddalia
asiatica (root bark), Rhamnus prinoides (leaves and root bark) and Vernonia
lasiopus (root bark) showed high chemosuppression in the range 51%/75%. Maytenus
acuminata, M. heterophylla, M. senegalensis and Rhamnus staddo had moderate
activities of 33%/49% parasitaemia suppression in the root bark and/or leaf
extracts, while Withania somnifera (root bark) had a non/significant suppression
(21%). In combination with CQ, extracts of V. lasiopus (all parts), leaf
extracts of M. senegalensis, R. prinoides and T. asiatica as well as root barks
of M. heterophylla, R. staddo and T. asiatica had improved parasitaemia
suppression in the range 38%/66%, indicating synergistic interactions.
Remarkable parasitaemia suppression by the extracts, either alone or in
combination with CQ resulted into longer survival of mice relative to the
controls, in some cases by more than 2 weeks. Plants, which showed significant
antimalarial activity including V. lasiopus, T. asiatica and R. prinoides,
should further be evaluated in the search for novel agents against
drug/resistant malaria. Copyright (c) 2007 John Wiley & Sons, Ltd.
PMID: 17221829 [PubMed / as supplied by publisher]
4: Chem Biodivers. 2004 Sep;1(9):1289/95.
Cholinesterase/inhibiting withanolides from Ajuga bracteosa.
Riaz N, Malik A; Aziz/ur/Rehman; Nawaz SA, Muhammad P, Choudhary MI.
International Centre for Chemical Sciences, H.E.J. Research Institute of
Chemistry, University of Karachi, Karachi/75270, Pakistan.
Three new withanolides, bracteosin A (= (22R)/5beta,6beta :
22,26/diepoxy/4beta,28/dihydroxy/3beta/methoxyergost/24/ene/1,26/dione; 1),
bracteosin B (= (22R)/5beta,6beta :
22,26/diepoxy/4beta,28/dihydroxy/3beta/methoxy/1,26/dioxoergost/24/en/19/oic
acid; 2), and bracteosin C (=
(22R)/22,26/epoxy/4beta,6beta,27/trihydroxy/3beta/methoxyergost/24/ene/1,26/dion
e; 3), have been isolated from the whole plants of Ajuga bracteosa. Their
structures were deduced by spectral analysis, including 1D/ and 2D/NMR
techniques. In addition, dihydroclerodin/1, clerodinin A, lupulin A, and
dihydroajugapitin have also been isolated for the first time from this species.
Compounds 1/3 exhibited evident inhibitory potential against cholinesterase
enzymes in a concentration/dependent fashion.
PMID: 17191906 [PubMed / indexed for MEDLINE]
5: J Nat Prod. 2006 Dec;69(12):1790/2.
Ashwagandhanolide, a bioactive dimeric thiowithanolide isolated from the roots
of Withania somnifera.
Subbaraju GV, Vanisree M, Rao CV, Sivaramakrishna C, Sridhar P, Jayaprakasam B,
Nair MG.
Laila Research Center, Unit I, Phase III, Jawahar Autonagar, Vijayawada 520 007,
India. subbarajugottumukkala@hotmail.com
A new dimeric withanolide, ashwagandhanolide (1), was isolated from the roots of
an Ayurvedic medicinal herb, Withania somnifera. A detailed spectroscopic
evaluation revealed its identity as a dimer with an unusual thioether linkage.
Compound 1 displayed growth inhibition against human gastric (AGS), breast
(MCF/7), central nervous system (SF/268), colon (HCT/116), and lung (NCI H460)
cancer cell lines, with IC50 values in the range 0.43/1.48 microg/mL. In
addition, it inhibited lipid peroxidation and the activity of the enzyme
cyclooxygenase/2 in vitro.
PMID: 17190461 [PubMed / indexed for MEDLINE]
6: Cancer Res. 2007 Jan 1;67(1):246/53. Epub 2006 Dec 21.
Par/4/dependent apoptosis by the dietary compound withaferin A in prostate
cancer cells.
Srinivasan S, Ranga RS, Burikhanov R, Han SS, Chendil D.
Department of Clinical Sciences, College of Health Sciences, University of
Kentucky, 900 South Limestone Street, Lexington, KY 40536, USA.
Deletion or mutation of the androgen receptor (AR) renders prostate tumors
refractory to apoptosis by androgen ablation, the mainstay of prostate cancer
therapy. To identify novel therapeutics that can induce apoptosis regardless of
the AR status of prostate cancer cells, we screened dietary herbal compounds
using a reporter assay for the prostate apoptosis response/4 (Par/4) gene, which
induces p53/ and PTEN/independent and cancer/selective apoptosis. One of the
compounds, withaferin A (WA), a major constituent of the dietary compound
Withania somnifera, induced Par/4/dependent apoptosis in androgen/refractory
prostate cancer cells and regression of PC/3 xenografts in nude mice.
Interestingly, restoration of wild/type AR in PC/3 (AR negative) cells abrogated
both Par/4 induction and apoptosis by WA. Individually, WA and anti/androgens
induced neither Par/4 nor apoptosis in androgen/responsive prostate cancer
cells, yet in combination, WA and anti/androgen synergistically induced Par/4
and apoptosis in androgen/responsive prostate cancer cells. Thus, when
judiciously combined with anti/androgens, WA inhibits survival of both
androgen/responsive and androgen/refractory prostate cancer cells by a
Par/4/dependent mechanism. As Par/4 up/regulation induces apoptosis in most
tumor cells, our findings can be extended to high/throughput screens to identify
synergistic combinations for both therapy/sensitive and therapy/resistant
cancers.
Publication Types:
Research Support, Non/U.S. Gov't
Research Support, U.S. Gov't, Non/P.H.S.
PMID: 17185378 [PubMed / indexed for MEDLINE]
7: Altern Med Rev. 2006 Dec;11(4):269/77.
Ancient medicine, modern use: Withania somnifera and its potential role in
integrative oncology.
Winters M.
Withania somnifera Dunal, commonly known as ashwagandha, has been used for
centuries in Ayurvedic medicine to increase longevity and vitality. Western
research supports its polypharmaceutical use, confirming antioxidant,
anti/inflammatory, immune/modulating, and antistress properties in the whole
plant extract and several separate constituents. This article reviews the
literature pertaining to Withania somnifera and its botanical constituents as
antitumor agents and in conjunction with radiation and chemotherapy treatment.
Following a search of MEDLINE and EBSCO databases, it can be concluded that
Withania somnifera reduces tumor cell proliferation while increasing overall
animal survival time. Furthermore, it has been shown to enhance the
effectiveness of radiation therapy while potentially mitigating undesirable side
effects. Withania somnifera also reduces the side effects of chemotherapeutic
agents cyclophosphamide and paclitaxel without interfering with the
tumor/reducing actions of the drugs. These effects have been demonstrated in
vitro on human cancer cell lines, and in vivo on animal subjects, but there have
been no human trials to date. Given its broad spectrum of cytotoxic and
tumor/sensitizing actions, Withania somnifera presents itself as a novel
complementary therapy for integrative oncology care.
Publication Types:
Review
PMID: 17176166 [PubMed / indexed for MEDLINE]
8: J Biol Chem. 2007 Feb 16;282(7):4253/4264. Epub 2006 Dec 6.
Withaferin A Strongly Elicits I{kappa}B Kinase beta Hyperphosphorylation
Concomitant with Potent Inhibition of Its Kinase Activity.
Kaileh M, Vanden Berghe W, Heyerick A, Horion J, Piette J, Libert C, De
Keukeleire D, Essawi T, Haegeman G.
Laboratory of Eukaryotic Gene Expression and Signal Transduction (LEGEST),
Department of Molecular Biology, Ghent University/UGent, K. L. Ledeganckstraat
35, B/9000 Gent, Belgium, Master program in Clinical Laboratory Sciences,
Birzeit University, P. O. Box 14, Birzeit, Palestine, Center for Biomedical
Integrated Genoproteomics (CBIG), Virology and Immunology Unit, Institute of
Pathology B23, B/4000 Liege, Belgium, Department of Molecular Biomedical
Research, Flanders Interuniversity for Biotechnology and Ghent University,
Technologiepark 927, B/9052 Zwijnaarde, Belgium, and Laboratory of Pharmacognosy
and Phytochemistry, Ghent University/UGent, Harelbekestraat 72, B/9000 Gent,
Belgium.
The transcription factor NFkappaB plays a critical role in normal and
pathophysiological immune responses. Therefore, NFkappaB and the signaling
pathways that regulate its activation have become a major focus of drug
development programs. Withania somnifera (WS) is a medicinal plant that is
widely used in Palestine for the treatment of various inflammatory disorders. In
this study we show that the leave extract of WS, as well as its major
constituent withaferin A (WA), potently inhibits NFkappaB activation by
preventing the tumor necrosis factor/induced activation of IkappaB kinase beta
via a thioalkylation/sensitive redox mechanism, whereas other WS/derived
steroidal lactones, such as withanolide A and 12/deoxywithastramonolide, are far
less effective. To our knowledge, this is the first communication of IkappaB
kinase beta inhibition by a plant/derived inhibitor, coinciding with
MEK1/ERK/dependent Ser/181 hyperphosphorylation. This prevents IkappaB
phosphorylation and degradation, which subsequently blocks NFkappaB
translocation, NFkappaB/DNA binding, and gene transcription. Taken together, our
results indicate that pure WA or WA/enriched WS extracts can be considered as a
novel class of NFkappaB inhibitors, which hold promise as novel
anti/inflammatory agents for treatment of various inflammatory disorders and/or
cancer.
PMID: 17150968 [PubMed / as supplied by publisher]
9: J Ethnopharmacol. 2006 Nov 15; [Epub ahead of print]
Antimalarial activity of methanolic extracts from plants used in Kenyan
ethnomedicine and their interactions with chloroquine (CQ) against a CQ/tolerant
rodent parasite, in mice.
Muregi FW, Ishih A, Miyase T, Suzuki T, Kino H, Amano T, Mkoji GM, Terada M.
Department of Parasitology, Hamamatsu University School of Medicine, 1/20/1
Handayama, Hamamatsu 431/3192, Japan; Centre for Biotechnology Research and
Development, Kenya Medical Research Institute (KEMRI), P.O. Box 54840/00200,
Nairobi, Kenya.
Methanolic extracts from 15 medicinal plants representing 11 families, used
traditionally for malaria treatment in Kenya were screened for their in vivo
antimalarial activity in mice against a chloroquine (CQ)/tolerant Plasmodium
berghei NK65, either alone or in combination with CQ. The plant parts used
ranged from leaves (L), stem bark (SB), root bark (RB), seeds (S) and whole
plant (W). When used alone, extracts from seven plants, Clerodendrum myricoides
(RB), Ficus sur (L/SB/RB), Maytenus acuminata (L/RB), Rhamnus prinoides (L/RB),
Rhamnus staddo (RB), Toddalia asiatica (RB) and Vernonia lasiopus (RB) had
statistically significant parasitaemia suppressions of 31.7/59.3%. In
combination with CQ, methanolic extracts of Albizia gummifera (SB), Ficus sur
(RB), Rhamnus prinoides and Rhamnus staddo (L/RB), Caesalpinia volkensii (L),
Maytenus senegalensis (L/RB), Withania somnifera (RB), Ekebergia capensis
(L/SB), Toddalia asiatica (L/RB) and Vernonia lasiopus (L/SB/RB) gave
statistically significant and improved suppressions which ranged from 45.5 to
85.1%. The fact that these activities were up to five/fold higher than that of
extract alone may suggest synergistic interactions. Remarkable parasitaemia
suppression by the extracts, either alone or in combination with CQ mostly
resulted into longer mouse survival relative to the controls, in some cases by a
further 2 weeks. Plants, which showed significant antimalarial activity
including Vernonia lasiopus, Toddalia asiatica, Ficus sur, Rhamnus prinoides and
Rhamnus staddo warrant further evaluation in the search for novel antimalarial
agents against drug/resistant malaria.
PMID: 17145149 [PubMed / as supplied by publisher]
10: Plant Cell Rep. 2006 Nov 15; [Epub ahead of print]
Changes in morphological phenotypes and withanolide composition of
Ri/transformed roots of Withania somnifera.
Bandyopadhyay M, Jha S, Tepfer D.
Centre of Advanced Study in Cell and Chromosome Research, Department of Botany,
University of Calcutta, 35 Ballygunge Circular Road, Calcutta, 700019, India,
sjbot@caluniv.ac.in.
Developmental variability was introduced into Withania somnifera using genetic
transformation by Agrobacterium rhizogenes, with the aim of changing
withasteroid production. Inoculation of W. somnifera with A. rhizogenes strains
LBA 9402 and A4 produced typical transformed root lines, transformed callus
lines, and rooty callus lines with simultaneous root dedifferentiation and
redifferentiation. These morphologically distinct transformed lines varied in
T/DNA content, growth rates, and withasteroid accumulation. All of the lines
with the typical transformed root morphology contained the T(L) T/DNA, and 90%
of them carried the T(R) T/DNA, irrespective of the strain used for infection.
Accumulation of withaferin A was maximum (0.44% dry weight) in the transformed
root line WSKHRL/1. This is the first detection of withaferin A in the roots of
W. somnifera. All of the rooty callus lines induced by strain A4 contained both
the T(L) and the T(R)/DNAs. In contrast, 50% of the rooty/callus lines obtained
with strain LBA 9402 contained only the T(R) T/DNA. All the rooty callus lines
accumulated both withaferin A and withanolide D. The callusing lines induced by
LBA 9402 lacked the T(L) T/DNA genes, while all the callusing lines induced by
strain A4 contained the T(L) DNA. Four of these callus lines produced both
withaferin A (0.15/0.21% dry weight) and withanolide D (0.08/0.11% dry weight),
and they grew faster than the transformed root lines. This is the first report
of the presence of withasteroids in undifferentiated callus cultures of W.
somnifera.
PMID: 17103214 [PubMed / as supplied by publisher]
11: Chem Biol Interact. 2006 Dec 15;164(3):174/80. Epub 2006 Nov 7.
Suppressive effect of Withania somnifera root powder on experimental gouty
arthritis: An in vivo and in vitro study.
Rasool M, Varalakshmi P.
Faculty of Biosciences, School of Bioengineering and Biosciences, Vellore
Institute of Technology (Deemed University), Vellore 632014, Tamil Nadu, India.
mkr474@rediffmail.com
The effect of Withania somnifera L. Dunal root powder on paw volume and serum
lysosomal enzyme activities was investigated in monosodium urate crystal/induced
rats. The levels of beta/glucuronidase and lactate dehydrogenase were also
measured in monosodium urate crystal incubated polymorphonuclear leucocytes
(PMNL). A significant increase in the level of paw volume and serum lysosomal
enzymes was observed in monosodium urate crystal/induced rats. The increased
beta/glucuronidase and lactate dehydrogenase level were observed in untreated
monosodium urate crystal incubated polymorphonuclear leucocytes. On treatment
with the W. somnifera root powder (500/1000 mg/kg body weight), the above
changes were reverted back to near normal levels. W. somnifera also showed
potent analgesic and antipyretic effect with the absence of gastric damage at
different dose levels in experimental rats. For comparison purpose,
non/steroidal anti/inflammatory drug (NSAID) indomethacin was used as a
standard. These results provide evidence for the suppressive effect of W.
somnifera root powder by retarding amplification and propagation of the
inflammatory response without causing any gastric damage.
PMID: 17084827 [PubMed / indexed for MEDLINE]
12: J Clin Rheumatol. 2004 Oct;10(5):236/245.
A 32/Week Randomized, Placebo/Controlled Clinical Evaluation of RA/11, an
Ayurvedic Drug, on Osteoarthritis of the Knees.
Chopra A, Lavin P, Patwardhan B, Chitre D.
From the *Center for Rheumatic Diseases, Inlaks and Budhrani Hospital, Bharati
Hospital Medical College (Deemed University), Pune, India; daggerAverion, Inc.,
Framingham, Massachusetts; the double daggerSchool of Health Sciences,
University of Pune, India; and section signBIO/VED Pharmaceuticals, Inc., San
Jose, California.
BACKGROUND:: The ancient Indian (Asian) Ayurvedic medicinal system uses
herbomineral drugs to treat arthritis. Despite centuries of use, very few have
been tested by drug trials. RA/11 (ARTREX, MENDAR), a standardized multiplant
Ayurvedic drug (Withania somnifera, Boswellia serrata, Zingiber officinale, and
Curcuma longa) is currently used to treat arthritis. OBJECTIVE:: The objective
of this study was to evaluate the efficacy and safety of RA/11 in patients with
symptomatic osteoarthritis (OA) of the knees. METHODS:: A total of 358 patients
with chronic knee pain were screened free/of/cost in "arthritis camps" in an
Indian metropolis. Ninety patients with primary OA of the knees (ACR
classification; Arthritis Rheum 1986;29:1039/1049) were found eligible
(postanalgesic washout pain visual analog score [VAS] >/=40 mm in either or both
knees on body weight/bearing activities) to enroll into a randomized,
double/blind, placebo/controlled, parallel efficacy, single/center, 32/week drug
trial (80% power to detect 25% difference, P = 0.05, 2/sided). Concurrent
analgesics/nonsteroidal antiinflammatory drugs and steroids in any form were not
allowed. Lifestyle and/or dietary restrictions, as per routine Ayurveda
practices, were not imposed. Pain VAS (maximum pain in each knee recorded by the
patient during the preceding 48 hours) and modified WOMAC (Western Ontario
McMaster University OA Index, Likert scale, version 3.0) were the primary
efficacy variables. The WOMAC section on "physical function difficulty" was
modified for Indian use and validated before the trial. Routine laboratory
testing was primarily done to monitor drug safety. At baseline, the groups
(active = 45, placebo = 45) were well matched for several measures (mean pain
VAS: active = 6.17; placebo = 6.5). RESULTS:: 1) Efficacy: Compared with
placebo, the mean reduction in pain VAS at week 16 (active = 2.7, placebo = 1.3)
and week 32 (active = 2.8, placebo = 1.8) in the active group was significantly
(P <0.05, analysis of variance [ANOVA]) better. Similarly, the improvement in
the WOMAC scores at week 16 and week 32 were also significantly superior (P
<0.01, ANOVA) in the active group. 2) Safety: Both the groups reported mild
adverse events (AE) without any significant difference. 3) Withdrawals:
Twenty/eight patients were discontinued. None reported drug/related toxicity.
The majority failed follow up/compliance. No differences were observed between
the groups. CONCLUSION:: This controlled drug trial demonstrates the potential
efficacy and safety of RA/ 11 in the symptomatic treatment of OA knees over 32
weeks of therapy.
PMID: 17043520 [PubMed / as supplied by publisher]
13: Ann Transplant. 2005;10(4):6/10.
The new approaches to preservation of graft cell integrity in preservation for
transplantation.
Gewartowska M, Olszewski WL.
Department of Surgical Research and Transplantology, Medical Research Center,
Polish Academy of Sciences, Warsaw, Poland.
Restoration of cell plasma membrane integrity after injury is essential for the
survival of animal cells. In case of graft preservation or during chemotherapy
in cancer, cell membrane integrity and the process of its repair are disrupted.
Cytoprotective substances are important in such cases, as well as in other
diseases, for example in myocardial infarction, acute insults and in chronic
neurodegenerative diseases. Hyperosmolarity is a condition in which cell
membrane stability may be damaged in vivo but preserved in the in vitro
conditions. Hypertonicity causes water leaving from cells by osmosis, decreasing
cell volume and increasing of intracellular ionic strength. High intracellular
ionic strength perturbs cellular function by decreasing the rates of biochemical
reaction. We review the new experimentally studied cytoprotective substances and
their application in cell membrane protection. Moreover, we present our data on
the effects of hyperosmolarity and its protective effect on cell internal
structure.
Publication Types:
Review
PMID: 17037081 [PubMed / indexed for MEDLINE]
14: Lett Appl Microbiol. 2006 Nov;43(5):469/74.
Inhibition of aflatoxin B production of Aspergillus flavus, isolated from
soybean seeds by certain natural plant products.
Krishnamurthy YL, Shashikala J.
Department of P.G. Studies and Research in Applied Botany, Kuvempu University,
Shankaraghatta, Shimoga District, Karnataka, India. murthy_ylk@yahoo.co.in
AIMS: The inhibitory effect of cowdung fumes, Captan, leaf powder of Withania
somnifera, Hyptis suaveolens, Eucalyptus citriodora, peel powder of Citrus
sinensis, Citrus medica and Punica granatum, neem cake and pongamia cake and
spore suspension of Trichoderma harzianum and Aspergillus niger on aflatoxin
B(1) production by toxigenic strain of Aspergillus flavus isolated from soybean
seeds was investigated. METHODS AND RESULTS: Soybean seed was treated with
different natural products and fungicide captan and was inoculated with
toxigenic strain of A. flavus and incubated for different periods. The results
showed that all the treatments were effective in controlling aflatoxin B(1)
production. Captan, neem cake, spore suspension of T. harzianum, A. niger and
combination of both reduced the level of aflatoxin B(1) to a great extent. Leaf
powder of W. somnifera, H. suaveolens, peel powder of C. sinensis, C. medica and
pongamia cake also controlled the aflatoxin B(1) production. CONCLUSIONS: All
the natural product treatments applied were significantly effective in
inhibiting aflatoxin B(1) production on soybean seeds by A. flavus. SIGNIFICANCE
AND IMPACT OF THE STUDY: These natural plant products may successfully replace
chemical fungicides and provide an alternative method to protect soybean and
other agricultural commodities from aflatoxin B(1) production by A. flavus.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 17032218 [PubMed / indexed for MEDLINE]
15: Int J Oncol. 2006 Nov;29(5):1269/78.
Chemopreventative strategies targeting the MGMT repair protein: augmented
expression in human lymphocytes and tumor cells by ethanolic and aqueous
extracts of several Indian medicinal plants.
Niture SK, Rao US, Srivenugopal KS.
Center for Cancer Biology, Department of Pharmaceutical Sciences, Texas Tech
University Health Sciences Center, Amarillo, TX 79106, USA.
O6/alkylguanines are potent mutagenic, pro/carcinogenic and cytotoxic lesions
induced by exogenous and endogenous alkylating agents. A facilitated elimination
of these lesions by increasing the activity of O6/methylguanine/DNA
methyltransferase (MGMT) is likely to be a beneficial chemoprevention strategy,
which, however, has not been examined. Because, a marginal enhancement of this
protein may be adequate for genomic protection, we studied alterations in MGMT
activity and expression in human peripheral blood lymphocytes and cancer cell
lines induced by water/soluble and alcohol/soluble constituents of several
plants with established antioxidant and medicinal properties. Both the ethanolic
and aqueous extracts from neem (Azadirachta indica), holy basil (Ocimum
sanctum), winter cherry (Withania somnifera), and oregano (Origanum majorana)
increased the levels of MGMT protein and its demethylation activity in a
time/dependent manner with a maximum of 3/fold increase after 72/h treatment.
The extracts from gooseberry (Emblica officinalis), common basil (Ocimum
basilicum), and spearmint (Mentha viridis) were relatively less efficient in
raising MGMT levels. Increased levels of MGMT mRNA accounted at least, in part,
for the increased activity of the DNA repair protein. The herbal treatments also
increased glutathione S/transferase/pi (GSTP1) expression, albeit to a lesser
extent than MGMT. These data provide the first evidence for the upregulation of
human MGMT by plant constituents and raise the possibility of rational dietary
approaches for attenuating alkylation/induced carcinogenesis. Further, they
reveal the putative antioxidant responsiveness of the MGMT gene in human cells.
Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non/U.S. Gov't
PMID: 17016661 [PubMed / indexed for MEDLINE]
16: Biofactors. 2006;27(1/4):53/67.
Enhanced cardiovascular function and energy level by a novel chromium
(III)/supplement.
Thirunavukkarasu M, Penumathsa S, Juhasz B, Zhan L, Bagchi M, Yasmin T, Shara
MA, Thatte HS, Bagchi D, Maulik N.
Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery,
University of Connecticut Medical Center, 263 Farmington Avenue, Farmington, CT
06030, USA.
The impetus for the novel Energy Formula (EF) which combines the niacin/bound
chromium (III) (0.45%) (NBC), standardized extract of Withania somnifera
extracts (10.71%), caffeine (22.76%), D/ribose (10.71%) and selected amino acids
such as phenylalanine, taurine and glutamine (55.37%) was based on the knowledge
of the cardioprotective potentials of the Withania somnifera extract, caffeine
and D/ribose as well as their abilities to increase energy levels and the
abilities of amino acids to increase the muscle mass and energy levels. The
effect of oral supplementation of EF on the safety, myocardial energy levels and
cardioprotective ability were investigated in an ischemic/reperfused myocardium
model in both male and female Sprague/Dawley rats over 90 days trial period. At
the completion of 90 days, the EF/treated male and female rats gained 9.4% and
3.1% less body weights, respectively, as compared to their corresponding control
groups. No significant difference was found in the levels of lipid peroxidation
and activities of hepatic Aspartate transaminase, Alanine transaminase and
Alkaline phosphatase in EF treatment when compared with control animals. The
male and female rat hearts were subjected to 30 min of global ischemia followed
by 2 h of reperfusion at 30 and 90 days of EF treatment. Cardiovascular
functions including heart rate, coronary flow, aortic flow, dp/dt(max), left
ventricular developed pressure (LVDP) and infarct size were monitored. The
levels of myocardial adenosine triphosphate (ATP), creatine phosphate (CP),
phospho/adenosine monophosphate kinase (p/AMPK) levels, were analyzed at the end
of 30 and 90 days of treatment. Significant improvement was observed in all
parameters in the EF treatment groups as compared to their corresponding
controls. Thus the niacin/bound chromium (III) based energy formula is safe and
effective supplement to boost energy levels and cardioprotection.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 17012764 [PubMed / in process]
17: J Basic Microbiol. 2006;46(5):365/74.
Antimicrobial properties of a non/toxic glycoprotein (WSG) from Withania
somnifera (Ashwagandha).
Girish KS, Machiah KD, Ushanandini S, Harish Kumar K, Nagaraju S, Govindappa M,
Vedavathi M, Kemparaju K.
Department of Biochemistry, University of Mysore, Manasagangothri, Mysore/560
006, India.
A monomeric glycoprotein with a molecular mass of 28 kDa in SDS/PAGE was
isolated from the Withania somnifera root tubers. The protein designated WSG
(Withania somnifera glycoprotein) demonstrated potent antimicrobial activity
against the phytopathogenic fungi and bacteria tested. Antifungal effect has
been demonstrated in that WSG exerts a fungistastic effect by inhibiting spore
germination and hyphal growth in the tested fungi. WSG showed potent antifungal
activity against Aspergillus flavus, Fusarium oxysporum, F. verticilloides and
antibacterial activity against Clvibacter michiganensis subsp. michiganensis.
WSG is an acidic, non/toxic (trypsin/chymotrypsin) protease inhibitor. These
results encourage further studies of WSG as a potential therapeutic agent for
its antifungal activity.
PMID: 17009292 [PubMed / indexed for MEDLINE]
18: Mol Cell Biochem. 2006 Nov;292(1/2):13/7. Epub 2006 Sep 27.
Stabilization of membrane bound enzyme profiles and lipid peroxidation by
Withania somnifera along with paclitaxel on benzo(a)pyrene induced experimental
lung cancer.
Senthilnathan P, Padmavathi R, Magesh V, Sakthisekaran D.
Department of Medical Biochemistry, Dr. ALM Postgraduate Institute of Basic
Medical Sciences, University of Madras, Taramani, Chennai 600113, India.
The present study was aimed to evaluate the therapeutic effects of Withania
somnifera along with paclitaxel on lung tumor induced by benzo(a)pyrene in male
Swiss albino mice. The levels of ATPase enzymes and lipid peroxidation were
evaluated in lung cancer bearing mice, in erythrocyte membrane and tissues. The
extent of peroxidation was estimated by measuring the thiobarbituric
acid/reactive substances. Simultaneously the activities of different ATPases
(Na(+)/K(+)/ATPases, Mg(2+)/ATPases and Ca(2+)/ATPases) were determined. The
alterations of these enzyme activities in membrane and tissues were indicative
of the tumor formation caused by benzo(a)pyrene (50 mg/kg body weight, orally)
in cancer bearing animals. The activities of these enzymes were reversed to near
normal control values in animals treated with Withania somnifera (400 mg/kg
b.wt, orally) along with paclitaxel (33 mg/kg b.wt, i.p). Treatment with
Withania somnifera along with paclitaxel altered these damage mediated through
free radicals, and the treatment displays the protective role of these drugs by
inhibiting free radical mediated cellular damages. Over, based on the data
providing a correlation Withania somnifera along with paclitaxel provide
stabilization of membrane bound enzyme profiles and decreased lipid peroxidation
against benzo(a)pyrene induced lung cancer in mice.
PMID: 17003952 [PubMed / indexed for MEDLINE]
19: Phytochemistry. 2006 Oct;67(20):2269/76. Epub 2006 Sep 7.
Phytochemical and genetic analysis in selected chemotypes of Withania somnifera.
Dhar RS, Verma V, Suri KA, Sangwan RS, Satti NK, Kumar A, Tuli R, Qazi GN.
Regional Research Laboratory, RRL, Biotechnology Division, Canal Road, Jammu,
Tawi 180001, India.
The main active components and genetic profile of 15 selected accessions of
Withania somnifera Dunal. were analysed. Ethanolic extract of the dried
roots/leaves of the plant was concentrated under pressure at 50+//5 degrees C
and was analysed for main compounds (withanolides and withaferin A) by HPLC. All
the main components were found to be present in accessions (AGB 002, AGB 009,
RSS 009, RSS 033). Correlation of these main components with their genetic
factors, was undertaken using AFLP (amplified fragment length polymorphism)
markers. Among 64 primers 7 yielded optimum polymorphism. A total of 913
polymorphic peaks were generated using these primers. Jaccard's similarity
coefficient indicated that accessions having almost the same active compounds
clustered together. The present study demonstrates that AFLP can be successfully
used to resolve the correlation of AFLP data with the presence of secondary
metabolites.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 16956635 [PubMed / indexed for MEDLINE]
20: J Ethnopharmacol. 2007 Jan 19;109(2):359/63. Epub 2006 Aug 4.
Screening of selected Indian medicinal plants for acetylcholinesterase
inhibitory activity.
Vinutha B, Prashanth D, Salma K, Sreeja SL, Pratiti D, Padmaja R, Radhika S,
Amit A, Venkateshwarlu K, Deepak M.
Department of Pharmacognosy, Al/Ameen College of Pharmacy, Hosur Road,
Bangalore, India.
Seventy/six plant extracts including methanolic and successive water extracts
from 37 Indian medicinal plants were investigated for acetylcholinesterase
(AChE) inhibitory activity (in vitro). Results indicated that methanolic
extracts to be more active than water extracts. The potent AChE inhibiting
methanolic plant extracts included Withania somnifera (root), Semecarpus
anacardium (stem bark), Embelia ribes (Root), Tinospora cordifolia (stem), Ficus
religiosa (stem bark) and Nardostachys jatamansi (rhizome). The IC(50) values
obtained for these extracts were 33.38, 16.74, 23.04, 38.36, 73.69 and
47.21mug/ml, respectively. These results partly substantiate the traditional use
of these herbs for improvement of cognition.
PMID: 16950584 [PubMed / in process]
21: Invest Ophthalmol Vis Sci. 2006 Sep;47(9):4138/45.
Small molecule anti/angiogenic probes of the ubiquitin proteasome pathway:
potential application to choroidal neovascularization.
Bargagna/Mohan P, Ravindranath PP, Mohan R.
Department of Ophthalmology and Visual Sciences, University of Kentucky,
Lexington, KY 40536, USA.
PURPOSE: To characterize the angiogenic and inflammatory responses of human
choroidal endothelial cells (HCECs) to stimulators and inhibitors of the
ubiquitin proteasome pathway (UPP). METHODS: The regulation of the UPP by the
inhibitor withaferin A and its congener, withanolide D, two natural products
derived from the medicinal plant Withania somnifera was assessed in the
three/dimensional endothelial cell sprouting assay (3D/ECSA), by using HCEC/ and
human umbilical vein endothelial cell (HUVEC)/derived spheroids embedded in a
collagen I matrix. Western blot analysis was used to investigate the effect of
withanolides on IkappaB/alpha, polyubiquitination, and heme oxygenase (HO)/1
regulation in HCEC and HUVEC cultures. RESULTS: HCECs, like HUVECs, responded to
fibroblast growth factor/2, vascular endothelial growth factor, and tumor
necrosis factor (TNF)/alpha stimulation and sprouted vessel/like structures in
collagen I matrix. However, HCECs were slower to generate these sprouting
vessels, when compared with HUVECs. The extent of inhibition of endothelial cell
sprouting in 3D matrix, the blockade of TNF/alpha/induced IkappaB/alpha
degradation, levels of global polyubiquitinated proteins, and induced production
of HO/1 in response to treatment by the withanolides in cultured endothelial
cells was similarly regulated between HCECs and HUVECs. CONCLUSIONS: HCECs share
with HUVECs a similar response to UPP inhibitors, suggesting that this
well/conserved pathway that regulates angioinflammatory mechanisms could be
exploited for drug/targeting in the development of novel agents for CNV
treatment.
PMID: 16936134 [PubMed / indexed for MEDLINE]
22: Int Immunopharmacol. 2006 Oct;6(10):1535/42. Epub 2006 Apr 27.
Prophylactic administration of Withania somnifera extract increases host
resistance in Listeria monocytogenes infected mice.
Teixeira ST, Valadares MC, Goncalves SA, de Melo A, Queiroz ML.
Fisiopatologia Medica, Faculdade de Ciencias Medicas, FCM, Universidade Estadual
de Campinas, UNICAMP, Campinas, SP, Brazil.
In this study, we demonstrated that Withania somnifera L. extract (WSE) protects
mice from a lethal dose of Listeria monocytogenes when administered
prophylactically at 100, 250 and 500 mg/kg for 10 days, with survival rates up
to 30%. These doses also prevented the myelosuppression and the splenomegaly
caused by a sublethal infection with L. monocytogenes, due to increased numbers
of granulocyte/macrophage progenitors (CFU/GM) in the bone marrow. Investigation
of the production of colony/stimulating factors (CSFs) revealed increased
colony/stimulating activity (CSA) in the serum of normal and infected mice
pre/treated with WSE. Further studies to investigate the levels of
interferon/gamma (INF/gamma) and lymphocyte cell proliferation were undertaken.
We observed dose/dependent increases in cell proliferation and in the levels of
INF/gamma in mice infected with L. monocytogenes and treated with WSE. All
together, our results suggest that WSE indirectly modulates immune activity and
probably disengages Listeria/induced suppression of these responses by inducing
a higher reserve of myeloid progenitors in the bone marrow, proliferation of
lymphocytes and increased INF/gamma levels.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 16919825 [PubMed / indexed for MEDLINE]
23: Int Immunopharmacol. 2006 Sep;6(9):1394/403. Epub 2006 May 8.
Augmentation and proliferation of T lymphocytes and Th/1 cytokines by Withania
somnifera in stressed mice.
Khan B, Ahmad SF, Bani S, Kaul A, Suri KA, Satti NK, Athar M, Qazi GN.
Cell Biology Laboratory, Department of Pharmacology, Regional Research
Laboratory, Jammu Tawi 180001, India.
Stress has been associated with reports of both greater severity and
prolongation of diseases in patients with the infectious origin as well as other
immune/mediated diseases. Withania somnifera, an Indian medicinal plant used
widely in the treatment of many clinical conditions in India, was investigated
for its anti/stress properties using BALB/c mice subjected to chronic stress.
The study aimed to investigate chronic stress/induced alterations on Th1
lymphocyte subset distribution and corresponding cytokine secretion patterns.
Oral administration of chemically standardized and identified aqueous fraction
of W. somnifera root (WS) at the graded doses of 25, 50, 100 and 200 mg/kg p.o.
caused significant increase in the stress/induced depleted T/cell population and
increased the expression of Th1 cytokines in chronically stressed mice.
PMID: 16846833 [PubMed / indexed for MEDLINE]
24: Cancer Sci. 2006 Jul;97(7):658/64.
Chemotherapeutic efficacy of paclitaxel in combination with Withania somnifera
on benzo(a)pyrene/induced experimental lung cancer.
Senthilnathan P, Padmavathi R, Magesh V, Sakthisekaran D.
Department of Medical Biochemistry, ALM Postgraduate Institute of Basic Medical
Sciences, University of Madras, Taramani Campus, Chennai 600/113, India.
Lung cancer is one of the leading causes of cancer death in the world and is
notoriously difficult to treat effectively. In the present study, male Swiss
albino mice were divided into five groups of six animals each: group I animals
received corn oil orally and served as a control; group II cancer/induced
animals received benzo(a)pyrene (50 mg/kg bodyweight dissolved in corn oil,
orally) twice weekly for four successive weeks; group III cancer/bearing animals
(after 12 weeks of induction) were treated with paclitaxel (33 mg/kg bodyweight,
i.p.) once weekly for 4 weeks; group IV cancer/bearing animals were treated with
paclitaxel along with Withania somnifera (400 mg/kg bodyweight) orally once
weekly for 4 weeks; and group V animals constituted the drug control treated
with paclitaxel along with W. somnifera. The serum, lung and liver were
investigated biochemically for aryl hydrocarbon hydroxylase, gamma/glutamyl
transpeptidase, 5'/nucleotidase, lactate dehydrogenase and protein/bound
carbohydrate components (hexose, hexosamine and sialic acid). These enzyme
activities were increased significantly in cancer/bearing animals compared with
control animals. The elevation of these in cancer/bearing animals was indicative
of the persistent deteriorating effect of benzo(a)pyrene in cancer/bearing
animals. Our data suggest that paclitaxel, administered with W. somnifera, may
extend its chemotherapeutic effect through modulating protein/bound carbohydrate
levels and marker enzymes, as they are indicators of cancer. The combination of
paclitaxel with W. somnifera could effectively treat the benzo(a)pyrene/induced
lung cancer in mice by offering protection from reactive oxygen species damage
and also by suppressing cell proliferation.
PMID: 16827807 [PubMed / indexed for MEDLINE]
25: Mol Cancer Ther. 2006 Jun;5(6):1434/45.
Withanolides potentiate apoptosis, inhibit invasion, and abolish
osteoclastogenesis through suppression of nuclear factor/kappaB (NF/kappaB)
activation and NF/kappaB/regulated gene expression.
Ichikawa H, Takada Y, Shishodia S, Jayaprakasam B, Nair MG, Aggarwal BB.
Cytokine Research Laboratory, Department of Experimental Therapeutics, The
University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard,
Houston, TX 77030, USA.
The plant Withania somnifera Dunal (Ashwagandha), also known as Indian ginseng,
is widely used in the Ayurvedic system of medicine to treat tumors,
inflammation, arthritis, asthma, and hypertension. Chemical investigation of the
roots and leaves of this plant has yielded bioactive withanolides. Earlier
studies showed that withanolides inhibit cyclooxygenase enzymes, lipid
peroxidation, and proliferation of tumor cells. Because several genes that
regulate cellular proliferation, carcinogenesis, metastasis, and inflammation
are regulated by activation of nuclear factor/kappaB (NF/kappaB), we
hypothesized that the activity of withanolides is mediated through modulation of
NF/kappaB activation. For this report, we investigated the effect of the
withanolide on NF/kappaB and NF/kappaB/regulated gene expression activated by
various carcinogens. We found that withanolides suppressed NF/kappaB activation
induced by a variety of inflammatory and carcinogenic agents, including tumor
necrosis factor (TNF), interleukin/1beta, doxorubicin, and cigarette smoke
condensate. Suppression was not cell type specific, as both inducible and
constitutive NF/kappaB activation was blocked by withanolides. The suppression
occurred through the inhibition of inhibitory subunit of IkappaB alpha kinase
activation, IkappaB alpha phosphorylation, IkappaB alpha degradation, p65
phosphorylation, and subsequent p65 nuclear translocation. NF/kappaB/dependent
reporter gene expression activated by TNF, TNF receptor (TNFR) 1,
TNFR/associated death domain, TNFR/associated factor 2, and IkappaB alpha kinase
was also suppressed. Consequently, withanolide suppressed the expression of
TNF/induced NF/kappaB/regulated antiapoptotic (inhibitor of apoptosis protein 1,
Bfl/1/A1, and FADD/like interleukin/1beta/converting enzyme/inhibitory protein)
and metastatic (cyclooxygenase/2 and intercellular adhesion molecule/1) gene
products, enhanced the apoptosis induced by TNF and chemotherapeutic agents, and
suppressed cellular TNF/induced invasion and receptor activator of NF/kappaB
ligand/induced osteoclastogenesis. Overall, our results indicate that
withanolides inhibit activation of NF/kappaB and NF/kappaB/regulated gene
expression, which may explain the ability of withanolides to enhance apoptosis
and inhibit invasion and osteoclastogenesis.
Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non/U.S. Gov't
Research Support, U.S. Gov't, Non/P.H.S.
PMID: 16818501 [PubMed / indexed for MEDLINE]
26: Altern Med Rev. 2006 Jun;11(2):128/50.
Modulation of cytokine expression by traditional medicines: a review of herbal
immunomodulators.
Spelman K, Burns J, Nichols D, Winters N, Ottersberg S, Tenborg M.
Clinical Division, Department of Herbal Medicine, Tai Sophia Institute, 7750
Montpelier Road, Laurel, MD 20723, USA. spelman123@earthlink.net.
Modulation of cytokine secretion may offer novel approaches in the treatment of
a variety of diseases. One strategy in the modulation of cytokine expression may
be through the use of herbal medicines. A class of herbal medicines, known as
immunomodulators, alters the activity of immune function through the dynamic
regulation of informational molecules such as cytokines. This may offer an
explanation of the effects of herbs on the immune system and other tissues. For
this informal review, the authors surveyed the primary literature on medicinal
plants and their effects on cytokine expression, taking special care to analyze
research that utilized the multi/component extracts equivalent to or similar to
what are used in traditional medicine, clinical phytotherapy, or in the
marketplace. METHODOLOGY: MEDLINE, EBSCO, and BIOSIS were used to identify
research on botanical medicines, in whole or standardized form, that act on
cytokine activity through different models, i.e., in vivo (human and animal), ex
vivo, or in vitro. RESULTS: Many medicinal plant extracts had effects on at
least one cytokine. The most frequently studied cytokines were IL/1, IL/6, TNF,
and IFN. Acalypha wilkesiana, Acanthopanax gracilistylus, Allium sativum, Ananus
comosus, Cissampelos sympodialis, Coriolus versicolor, Curcuma longa, Echinacea
purpurea, Grifola frondosa, Harpagophytum procumbens, Panax ginseng, Polygala
tenuifolia, Poria cocos, Silybum marianum, Smilax glabra, Tinospora cordifolia,
Uncaria tomentosa, and Withania somnifera demonstrate modulation of multiple
cytokines. CONCLUSION: The in vitro and in vivo research demonstrates that the
reviewed botanical medicines modulate the secretion of multiple cytokines. The
reported therapeutic success of these plants by traditional cultures and modern
clinicians may be partially due to their effects on cytokines. Phytotherapy
offers a potential therapeutic modality for the treatment of many differing
conditions involving cytokines. Given the activity demonstrated by many of the
reviewed herbal medicines and the increasing awareness of the broad/spectrum
effects of cytokines on autoimmune conditions and chronic degenerative
processes, further study of phytotherapy for cytokine/related diseases and
syndromes is warranted.
Publication Types:
Review
PMID: 16813462 [PubMed / indexed for MEDLINE]
27: J Ethnopharmacol. 2006 Nov 3;108(1):152/4. Epub 2006 Apr 29.
An inventory of the ethnobotanicals used as anthelmintics in the southern Punjab
(Pakistan).
Jabbar A, Raza MA, Iqbal Z, Khan MN.
Ethnoveterinary Research and Development Centre, Department of Veterinary
Parasitology, University of Agriculture, Faisalabad/38040, Pakistan.
jabbaruaf@yahoo.co.uk
A survey was conducted in southern Punjab, Pakistan, in order to document
existing ethnobotanical knowledge by the herdsmen/key respondents about
anthelmintics in ruminants. A 3/satge process was used to document the plants
being used to treat and/or control helminthes. This paper describes 29 plants to
treat helminthosis in ruminants. The main plants used were Lamium amplexicaule
L., Mallotus philippinensis Muell., Withania somnifera (L.) Dunal., Azadirachta
indica A. Juss., and Citrullus colocynthis (L.) Schrad. A few of these plants
have been scientifically validated for their claim by herdsmen on modern lines
while majority of them still needs investigations. This documentation could
provide a foundation for the scientific study and verification of those plants
which merit such study.
PMID: 16730420 [PubMed / in process]
28: Vascul Pharmacol. 2006 Jun;44(6):406/10. Epub 2006 May 18.
Immunomodulatory role of Withania somnifera root powder on experimental induced
inflammation: An in vivo and in vitro study.
Rasool M, Varalakshmi P.
Department of Biosciences, Vellore Institute of Technology, Deemed University,
Vellore/632 014, India. mkr474@rediffmail.com
The aqueous suspension of Withania somnifera root powder was investigated for
their in vivo and in vitro immunomodulatory properties. W. somnifera showed
potent inhibitory activity towards the complement system, mitogen induced
lymphocyte proliferation and delayed/type hypersensitivity reaction.
Administration of W. somnifera root powder did not have a significant effect on
humoral immune response in rats. Our results report immunosuppressive effect of
W. somnifera root powder, thus it could be a candidate for developing as an
immunosuppressive drug for the inflammatory diseases.
PMID: 16713367 [PubMed / indexed for MEDLINE]
29: Phytomedicine. 2007 Feb;14(2/3):136/42. Epub 2006 May 18.
Hypocholesteremic and antioxidant effects of Withania somnifera (Dunal) in
hypercholesteremic rats.
Visavadiya NP, Narasimhacharya AV.
Department of Biosciences, Sardar Patel University, Vallabh Vidyanagar 388 120,
Gujarat, India.
Hypocholesteremic and antioxidant effects of Withania somnifera (WS) Dunal
(Solanaceae) were investigated in hypercholesteremic male albino rats. When the
root powder of WS was added to the diet at 0.75 and 1.5gm/rat/day,
hypercholesteremic animals registered significant decreases in total lipids
(/40.54%; /50.69%), cholesterol (/41.58%; /53.01%) and triglycerides (/31.25%; /
44.85%) in plasma. On the other hand, significant increases in plasma
HDL/cholesterol levels (+15.10%; +17.71%), HMG/CoA reductase activity (+19.51%;
+26.02%) and bile acid content (+24.64%; +30.52%) of liver were noted in these
animals. A similar trend was also noted in bile acid (+22.43%;+28.52%),
cholesterol (+14.21%; +17.68%) and neutral sterol (+12.40%; +18.85%) excretion
in the hypercholesteremic animals with WS administration. Further, a significant
decrease in lipid/peroxidation (/35.29%; /36.52%) occurred in WS administered
hypercholesteremic animals when compared to their normal counterparts. However,
it appeared that WS root powder is also effective in normal subjects for
decreasing lipid profiles.
PMID: 16713218 [PubMed / in process]
30: Phytother Res. 2006 Jul;20(7):614/7.
Hypolipidemic activity of aqueous extract of Withania coagulans Dunal in albino
rats.
Hemalatha S, Wahi AK, Singh PN, Chansouria JP.
Department of Pharmaceutics, Institute of Technology, Banaras Hindu University,
Varanasi 221005, India.
Administration of an aqueous extract of fruits of Withania coagulans (1 g/kg;
p.o.) to high fat diet induced hyperlipidemic rats for 7 weeks, significantly
reduced elevated serum cholesterol, triglycerides and lipoprotein levels. This
drug also showed hypolipidemic activity in triton induced hypercholesterolemia.
The histopathological examination of liver tissues of treated hyperlipidemic
rats showed comparatively lesser degenerative changes compared with
hyperlipidemic controls. The hypolipidemic effect of W. coagulans fruits was
found to be comparable to that of an Ayurvedic product containing Commiphora
mukkul.
PMID: 16691631 [PubMed / in process]
31: J Ethnopharmacol. 2006 Aug 11;107(1):107/15. Epub 2006 Apr 5.
Selective Th1 up/regulating activity of Withania somnifera aqueous extract in an
experimental system using flow cytometry.
Bani S, Gautam M, Sheikh FA, Khan B, Satti NK, Suri KA, Qazi GN, Patwardhan B.
Department of Pharmacology, Regional Research Laboratory, Jammu Tawi, India.
sarangbani@rediffmail.com
Withania somnifera (Ashwagandha) is reported to be immunoprotective and
immunoadjuvant. We studied its roots aqueous extract on T helper (Th) immunity
using flow cytometry. This extract was standardized with six withanolides as
marker compounds using HPLC. Once daily dose ranging from 25 to 400 mg/kg/p.o.
was used to study effect on Th1: IFN/gamma, IL/2 and Th2: IL/4 cytokine
modulation. We also studied effect on CD4 and CD8 in normal and immunesuppressed
mice. The results indicate that extract at 100 mg/kg resulted significant
selective up/regulation of Th1 response. Treatment with extract showed
significant increase in CD4 and CD8 counts as compared to control and
cyclopsorin A, with a faster recovery of CD4+ T cells in immunesuppressed
animals. Under immunesuppressed conditions, potentiation of cellular and humoral
immune responses of extract was comparable to levamisole. This study indicates
the selective Th1 up/regulating effect of extract and suggests its use for
selective Th1/Th2 modulation.
PMID: 16603328 [PubMed / indexed for MEDLINE]
32: J Pharm Pharmacol. 2006 Apr;58(4):513/9.
Withania somnifera improves bone calcification in calcium/deficient
ovariectomized rats.
Nagareddy PR, Lakshmana M.
Dept. of Pharmacology, Government College of Pharmacy, Bangalore, 560027, India.
reddy@interchange.ubc.ca
Osteoporosis, characterized by reduction in bone density, is a significant
source of mortality among the elderly, particularly in oestrogen/deficient
women. We studied the effect of Withania somnifera (WS) root extract
(ethanolic), which contains oestrogen/like withanolides for anti/osteoporotic
activity. Female Sprague/Dawley rats were either sham operated (n = 12) or
ovariectomized (n = 12) and treated with WS/vehicle (65 mg kg(/1)), orally for
16 weeks (n = 12). All rats were allowed free access to a calcium/deficient diet
(0.04% Ca) and distilled water. At termination, urinary excretion of calcium
(Ca) and phosphorus (P) and serum levels of Ca, P and alkaline phosphatase (ALP)
were measured. Femur and tibia bones were processed for histological
(histology), morphological (scanning electron microscopy, SEM), biomechanical
strength (impact test) and mineral composition (ash) analysis. Ovariectomized
(OVX) rats showed a significant increase in serum ALP levels and urinary Ca and
P excretion. Histological findings revealed narrowed, and disappearance of,
trabeculae with widened medullary spaces in the OVX group. Ash analysis showed a
reduction in ash weight, percent ash, ash Ca, ash P and ash magnesium levels in
the OVX group. Further, SEM examination revealed metaphyseal bone loss in femurs
and impact test showed a reduction in biomechanical strength of tibias in OVX
rats. WS treatment markedly prevented the above changes in OVX rats and thus may
be a potential agent in the treatment of osteoporosis.
Publication Types:
Comparative Study
Research Support, Non/U.S. Gov't
PMID: 16597369 [PubMed / indexed for MEDLINE]
33: Eur J Neurosci. 2006 Mar;23(6):1417/26.
Withanoside IV and its active metabolite, sominone, attenuate
Abeta(25/35)/induced neurodegeneration.
Kuboyama T, Tohda C, Komatsu K.
Division of Biofunctional Evaluation, Research Center for Ethnomedicine,
Institute of Natural Medicine, University of Toyama, Toyama 930/0194, Japan.
At the present, medication of dementia is limited to symptomatic treatments such
as the use of cholinesterase inhibitors. To cure dementia completely, that is
regaining neuronal function, reconstruction of neuronal networks is necessary.
Therefore, we have been exploring antidementia drugs based on reconstructing
neuronal networks in the damaged brain and found that withanoside IV (a
constituent of Ashwagandha; the root of Withania somnifera) induced neurite
outgrowth in cultured rat cortical neurons. Oral administration of withanoside
IV (10 micromol/kg/day) significantly improved memory deficits in
Abeta(25/35)/injected (25 nmol, i.c.v.) mice and prevented loss of axons,
dendrites, and synapses. Sominone, an aglycone of withanoside IV, was identified
as the main metabolite after oral administration of withanoside IV. Sominone (1
microM) induced axonal and dendritic regeneration and synaptic reconstruction
significantly in cultured rat cortical neurons damaged by 10 microM
Abeta(25/35). These data suggest that orally administrated withanoside IV may
ameliorate neuronal dysfunction in Alzheimer's disease and that the active
principle after metabolism is sominone.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 16553605 [PubMed / indexed for MEDLINE]
34: J Ethnopharmacol. 2006 Jul 19;106(3):403/7. Epub 2006 Mar 13.
Anti/plasmodial activity and toxicity of extracts of plants used in traditional
malaria therapy in Meru and Kilifi Districts of Kenya.
Kirira PG, Rukunga GM, Wanyonyi AW, Muregi FM, Gathirwa JW, Muthaura CN, Omar
SA, Tolo F, Mungai GM, Ndiege IO.
Department of Chemistry, School of Pure & Applied Sciences, Kenyatta University,
P.O. Box 43844, Nairobi 00100 GPO, Kenya.
The methanol and aqueous extracts of 10 plant species (Acacia nilotica,
Azadirachta indica, Carissa edulis, Fagaropsis angolensis, Harrissonia
abyssinica, Myrica salicifolia, Neoboutonia macrocalyx, Strychnos heningsii,
Withania somnifera and Zanthoxylum usambarensis) used to treat malaria in Meru
and Kilifi Districts, Kenya, were tested for brine shrimp lethality and in vitro
anti/plasmodial activity against chloroquine/sensitive and chloroquine/resistant
strains of Plasmodium falciparum (NF54 and ENT30). Of the plants tested, 40% of
the methanol extracts were toxic to the brine shrimp (LD(50)<100micro/ml), while
50% showed in vitro anti/plasmodial activity (IC(50)<100microg/ml). The methanol
extract of the stem bark of N. macrocalyx had the highest toxicity to brine
shrimp nauplii (LD(50) 21.04+//1.8microg/ml). Methanol extracts of the rest of
the plants exhibited mild or no brine shrimp toxicity (LD(50)>50microg/ml). The
aqueous extracts of N. macrocalyx had mild brine shrimp toxicity (LD(50)
41.69+//0.9microg/ml), while the rest were lower (LD(50)>100microg/ml). The
methanol extracts of F. angolensis and Zanthoxylum usambarense had IC(50) values
<6microg/ml while the aqueous ones had values between 6 and 15microg/ml, against
both chloroquine/sensitive and resistant P. falciparum strains. The results
support the use of traditional herbs for anti/malarial therapy and demonstrate
their potential as sources of drugs.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 16530996 [PubMed / indexed for MEDLINE]
35: Comp Biochem Physiol C Toxicol Pharmacol. 2006 Jun;143(2):158/61. Epub 2006
Mar 2.
A glycoprotein from a folk medicinal plant, Withania somnifera, inhibits
hyaluronidase activity of snake venoms.
Machiah DK, Girish KS, Gowda TV.
Department of Pathology, Emory School of Medicine, Atlanta, Georgia, USA.
Venom hyaluronidases help in rapid spreading of the toxins by destroying the
integrity of the extra/cellular matrix of the tissues in the victims. A
hyaluronidase inhibitor (WSG) is purified from a folk medicinal plant, Withania
somnifera. The glycoprotein inhibited the hyaluronidase activity of cobra (Naja
naja) and viper (Daboia russelii) venoms, which was demonstrated by zymogram
assay and staining of the skin tissues for differential activity. WSG completely
inhibited the activity of the enzyme at a concentration of 1:1 w/w of venom to
WSG. Thus we are able to demonstrate that the glycoprotein inhibits
hyaluronidase activity of the venoms. External application of the plant extract
as an antidote in rural parts of India to snakebite victims appears to have a
scientific basis.
Publication Types:
In Vitro
Research Support, Non/U.S. Gov't
PMID: 16513428 [PubMed / in process]
36: Biochimie. 2006 Jun;88(6):701/10. Epub 2006 Jan 26.
Purification of a post/synaptic neurotoxic phospholipase A2 from Naja naja venom
and its inhibition by a glycoprotein from Withania somnifera.
Machiah DK, Gowda TV.
Department of Infectious Disease, Emory University, Atlanta 30030 Georgia, USA.
A post/synaptic neurotoxic phospholipase A(2) (PLA(2)) has been purified from
Indian cobra Naja naja venom. It was associated with a peptide in the venom. The
association was disrupted using 8 M urea. It is denoted to be a basic protein by
its behavior on both ion exchange chromatography and electrophoresis. It is
toxic to mice, LD(50) 1.9 mg/kg body weight (ip). It is proved to be
post/synaptic PLA(2) by chymographic experiment using frog nerve/muscle
preparation. A glycoprotein, (WSG) was isolated from a folk medicinal plant
Withania somnifera. The WSG inhibited the phospholipase A(2) activity of
NN/XIa/PLA(2,) isolated from the cobra venom, completely at a mole/to/mole ratio
of 1:2 (NN/XIa/PLA(2): WSG) but failed to neutralize the toxicity of the
molecule. However, it reduced the toxicity as well as prolonged the death time
of the experimental mice approximately 10 times when compared to venom alone.
The WSG also inhibited several other PLA(2) isoforms from the venom to varying
extent. The interaction of the WSG with the PLA(2) is confirmed by fluorescence
quenching and gel/permeation chromatography. Chemical modification of the active
histidine residue of PLA(2) using p/brophenacyl bromide resulted in the loss of
both catalytic activity as well as neurotoxicity of the molecule. These findings
suggest that the venom PLA(2) has multiple sites on it; perhaps some of them are
overlapping. Application of the plant extract on snakebite wound confirms the
medicinal value associated with the plant.
Publication Types:
In Vitro
Research Support, Non/U.S. Gov't
PMID: 16494989 [PubMed / indexed for MEDLINE]
37: Phytomedicine. 2006 Mar;13(4):222/9. Epub 2005 Sep 27.
Protective effect of CardiPro against doxorubicin/induced cardiotoxicity in
mice.
Mohan IK, Kumar KV, Naidu MU, Khan M, Sundaram C.
Department of Clinical Pharmacology & Therapeutics, Nizam's Institute of Medical
Sciences, Punjagutta, Hyderabad, 500082, India.
The effect of CardiPro, a polyherbal formulation, with an antioxidant property,
has been studied on doxorubicin (DXR)/induced cardiotoxicity in mice. CardiPro
(150 mg/kg b.w., twice daily was administered orally for 7 weeks along with four
equal injections (each containing 4.0 mg/kg b.w., DXR) intraperitoneally, once
weekly (cumulative dose 16 mg/kg). After a 3/week post DXR treatment period,
cardiotoxicity was assessed by noting mortality, volume of ascites, liver
congestion, changes in heart weight, myocardial lipid peroxidation, antioxidant
enzymes and histology of heart. DXR/treated animals showed higher mortality
(50%) and more ascites. Myocardial SOD and glutathione peroxidase activity were
decreased and lipid peroxidation was increased. Histology of heart of
DXR/treated animals showed loss of myofibrils and focal cytoplasmic
vacuolization. CardiPro significantly protected the mice from DXR/induced
cardiotoxic effects as evidenced by lower mortality (25%), less ascites,
myocardial lipid peroxidation, normalization of antioxidant enzymes and minimal
damage to the heart histologically. Our data confirm the earlier reports that
DXR cardiotoxicity is associated with the free radical/induced tissue damage.
Administration of CardiPro, with an antioxidant property, protected the
DXR/induced cardiotoxicity in mice.
Publication Types:
Comparative Study
Research Support, Non/U.S. Gov't
PMID: 16492523 [PubMed / indexed for MEDLINE]
38: Phytother Res. 2006 Feb;20(2):140/6.
Effect of Withania somnifera root extract on reserpine/induced orofacial
dyskinesia and cognitive dysfunction.
Naidu PS, Singh A, Kulkarni SK.
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab
University, Chandigarh 160014, India.
Tardive dyskinesia is one of the major side effects of long/term neuroleptic
treatment. The pathophysiology of this disabling and commonly irreversible
movement disorder is still obscure. Vacuous chewing movements in rats are widely
accepted as an animal model of tardive dyskinesia. Oxidative stress and products
of lipid peroxidation are implicated in the pathophysiology of tardive
dyskinesia. Repeated treatment with reserpine (1.0 mg/kg) on alternate days for
a period of 5 days (days 1, 3 and 5) significantly induced vacuous chewing
movements and tongue protrusions in rats. Chronic treatment with Withania
somnifera root extract (Ws) for a period of 4 weeks to reserpine treated animals
significantly and dose dependently (50 and 100 mg/kg) reduced the
reserpine/induced vacuous chewing movements and tongue protrusions. Reserpine
treated animals also showed poor retention of memory in the elevated plus maze
task paradigm. Chronic Ws administration significantly reversed
reserpine/induced retention deficits. Biochemical analysis revealed that chronic
reserpine treatment significantly induced lipid peroxidation and decreased the
glutathione (GSH) levels in the brains of rats. Chronic reserpine treated rats
showed decreased levels of antioxidant defense enzymes, superoxide dismutase
(SOD) and catalase. Chronic administration of Ws root extract dose dependently
(50 and 100 mg/kg) and significantly reduced the lipid peroxidation and restored
the decreased glutathione levels by chronic reserpine treatment. It also
significantly reversed the reserpine/induced decrease in brain SOD and catalase
levels in rats. The major findings of the present study indicate that oxidative
stress might play an important role in the pathophysiology of reserpine/induced
abnormal oral movements. In conclusion, Withania somnifera root extract could be
a useful drug for the treatment of drug/induced dyskinesia. Copyright 2006 John
Wiley & Sons, Ltd.
PMID: 16444668 [PubMed / indexed for MEDLINE]
39: Indian J Exp Biol. 2006 Jan;44(1):45/8.
Effect of BR/16A (Mentat), a polyherbal formulation on drug/induced catalepsy in
mice.
Kumar A, Kulkarni SK.
University Institute of Pharmaceutical Science, Panjab University, Chandigarh
160 014, India.
Parkinson's disease (PD) is a neurodegenerative disease characterized by the
selective loss of dopamine (DA) neurons of the substantia nigra pars compacta
(SNc). The events, which trigger and/or mediate the loss of nigral DA neurons,
however, remain unclear. Neuroleptic/induced catalepsy has long been used as an
animal model for screening drugs for Parkinsonism. Administration of haloperidol
(1 mg/kg, ip) or reserpine (2 mg/kg, ip) significantly induced catalepsy in
mice. BR/16A (50 and 100 mg/kg, po), a polyherbal formulation or ashwagandha (50
and 100 mg/kg, po), significantly reversed the haloperidol or reserpine/induced
catalepsy. The results indicate that BR/16A or ashwagandha has protective effect
against haloperidol or reserpine/induced catalepsy and provide hope that BR/16A
could be used in preventing the drug/induced extrapyramidal side effects and may
offer a new therapeutic approach to the treatment of Parkinson's disease.
PMID: 16430090 [PubMed / indexed for MEDLINE]
40: J Ethnopharmacol. 2006 May 24;105(3):336/41. Epub 2006 Jan 10.
Evaluation of the effect of Withania somnifera root extracts on cell cycle and
angiogenesis.
Mathur R, Gupta SK, Singh N, Mathur S, Kochupillai V, Velpandian T.
Department of Pharmacology, All India Institute of Medical Sciences, Ansari
Nagar, New Delhi 110029, India.
In the Indian System of Medicine, the medicinal plant, Withania somnifera Dunal
(Solanaceae) finds application for numerous ailments including cancer. This
study explores the mechanism(s) underlying this property. The hydroalcoholic
extract of the roots (WS) was partitioned between chloroform (WS/chloroform) and
water (WS/water). Further, WS/chloroform was fractionated (A1/A12) by
reverse/phase column chromatography and their withanolide content was quantified
by high/performance liquid chromatography (HPLC). Preliminarily, the
anti/proliferative activity of all the extracts and fractions was screened
against human laryngeal carcinoma (Hep2) cells by microculture tetrazolium assay
(MTT). Two extracts (WS and WS/chloroform) and three fractions (A4, A5 and A6)
negatively affected Hep2 viability at the concentration of 25 microg/ml and
these were further investigated pharmacologically. Flow cytometry revealed cell
cycle block and accumulation of hypoploid (sub G1) cells as the mode of
anti/proliferative activity of all but A4. Their anti/angiogenic potential was
investigated by a chickchorio/allantoic membrane (CAM) wherein a significant
inhibition (p<0.0001) of vascular endothelium growth factor (VEGF), induced
neovascularization was recorded. The effect was confirmed in vivo by mouse
sponge implantation method. These findings suggest that the roots of Withania
somnifera possess cell cycle disruption and anti/angiogenic activity, which may
be a critical mediator for its anti/cancer action.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 16412596 [PubMed / indexed for MEDLINE]
41: J Plant Physiol. 2006 Feb;163(2):220/3. Epub 2005 Sep 2.
Regeneration of plants from alginate/encapsulated shoot tips of Withania
somnifera (L.) Dunal, a medicinally important plant species.
Singh AK, Varshney R, Sharma M, Agarwal SS, Bansal KC.
National Research Centre on Plant Biotechnology, Indian Agricultural Research
Institute, New Delhi/110 012, India.
A protocol was developed for plant regeneration from encapsulated shoot tips
collected from in vitro proliferated shoots of Withania somnifera. The best gel
composition was achieved using 3% sodium alginate and 75 mM CaCl2.2H2O. The
maximum percentage response (87%) for conversion of encapsulated shoot tips into
plantlets was achieved on MS medium supplemented with 0.5 mg/l IBA after 5 weeks
of culture. The conversion of encapsulated shoot tips into plantlets also
occurred when calcium alginate beads having entrapped propagules were directly
sown in autoclaved soilrite moistened with 14/MS salts.
PMID: 16399013 [PubMed / indexed for MEDLINE]
42: Ann N Y Acad Sci. 2005 Nov;1056:261/78.
Antiulcer and Antioxidant Activity of Asparagus racemosus WILLD and Withania
somnifera DUNAL in Rats.
Bhatnagar M, Sisodia SS, Bhatnagar R.
Department of Zoology, University College of Science, Mohan Lal Sukhadia
University, Udaipur/313001, India. mbhatnagar@yahoo.com.
Comparative study of the antiulcer and antisecretory activity of Asparagus
racemosus Willd (Shatawari) and Withania somnifera Dunal (Ashwagandha) root
extract with a standard drug, ranitidine, in various models of gastric ulcer in
rats is presented. Ulcer was induced by the indomethacin (NSAID) and swim
(restraint) stress treatment. Results demonstrated that A. racemosus as well as
W. somnifera methanolic extract (100 mg/kg BW/day p.o.) given orally for 15 days
significantly reduced the ulcer index, volume of gastric secretion, free
acidity, and total acidity. A significant increase in the total carbohydrate and
total carbohydrate/protein ratio was also observed. Study also indicated an
increase in antioxidant defense, that is, enzymes superoxide dismutase,
catalase, and ascorbic acid, increased significantly, whereas a significant
decrease in lipid peroxidation was observed. A. racemosus was more effective in
reducing gastric ulcer in indomethacin/treated gastric ulcerative rats, whereas
W. somnifera was effective in stress/induced gastric ulcer. Results obtained for
both herbal drugs were comparable to those of the standard drug ranitidine.
PMID: 16387694 [PubMed / in process]
43: Chem Biol Interact. 2006 Feb 25;159(3):180/5. Epub 2005 Dec 22.
Enhancement of antitumor effect of paclitaxel in combination with
immunomodulatory Withania somnifera on benzo(a)pyrene induced experimental lung
cancer.
Senthilnathan P, Padmavathi R, Banu SM, Sakthisekaran D.
Department of Medical Biochemistry, Dr. ALM Postgraduate Institute of Basic
Medical Sciences, University of Madras, Taramani, Chennai 600113, India.
senthilnpm@rediffmail.com
The current experimental work deals with the immunomodulatory studies on the
extract of Withania somnifera (L.) Dunal root powder against benzo(a)pyrene
induced lung cancer in male Swiss albino mice. In our previous study, we
reported the antioxidant and anticarcinogenic effect of W. somnifera (L.) Dunal
along with paclitaxel. Immune dysfunction has been found to be associated with
cancer and chemotherapy. Benzo(a)pyrene induced cancer animals were treated with
400mg/kg bodyweight of W. somnifera (L.) Dunal extract for 30 days significantly
alters the levels of immunocompetent cells, immune complexes and
immunoglobulins. Based on the data, the carcinogen as well as the paclitaxel
affects the immune system, the toxic side effects on the immune system is more
reversible and more controllable by W. somnifera (L.) Dunal. These results
concluded the immunomodulatory activity of W. somnifera (L.) Dunal extract,
which is a known immunomodulator in indigenous medicine.
PMID: 16375880 [PubMed / indexed for MEDLINE]
44: Ned Tijdschr Geneeskd. 2005 Nov 19;149(47):2637/8.
[Thyrotoxicosis following the use of ashwagandha]
[Article in Dutch]
van der Hooft CS, Hoekstra A, Winter A, de Smet PA, Stricker BH.
Inspectie voor de Gezondheidszorg, sectie Geneesmiddelenbewaking, Postbus
16.119, 2500 BC Den Haag.
A 32/year/old healthy woman developed thyrotoxicosis while taking capsules that
contained ashwagandha herbal extract for symptoms of chronic fatigue. She was
not taking any other remedies or medications. During the first few weeks, she
took the capsules only occasionally without any symptoms, but after increasing
the dose, she experienced clinical symptoms indicative of thyrotoxicosis. This
was confirmed by laboratory assessment. The symptoms resolved spontaneously
after discontinuation of the ashwagandha capsules and laboratory values
normalised. To our knowledge, this relationship has not been reported previously
in humans. Data from animal studies, however, have suggested that ashwagandha
can increase serum concentrations of thyroid hormones. This case study suggests
that thyrotoxicosis is a potentially serious side effect of ashwagandha.
Publication Types:
Case Reports
English Abstract
PMID: 16355578 [PubMed / indexed for MEDLINE]
45: Phytochemistry. 2005 Dec;66(23):2702/7. Epub 2005 Nov 15.
Unusually sulfated and oxygenated steroids from Withania somnifera.
Misra L, Lal P, Sangwan RS, Sangwan NS, Uniyal GC, Tuli R.
Central Institute of Medicinal and Aromatic Plants, P.O./CIMAP, Lucknow, UP 226
015, India. laxmisra@hotmail.com
Four (1, 8/10) and six known (2/7) withanolides were isolated from the leaves of
Withania somnifera. Among the new compounds, 10 possessed the rare 3/O/sulfate
group with the saturation in A ring and 9 contained unusual 1,4/dien/3/one
group. Compound 8 did not have usual 2,3 unsaturation in A ring while 1 had the
rare C/16 double bond. The structures of all the compounds were elucidated by
spectroscopic methods and chemical transformation.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 16293277 [PubMed / indexed for MEDLINE]
46: Life Sci. 2006 Jan 25;78(9):1010/4. Epub 2005 Sep 6.
Modulation of TCA cycle enzymes and electron transport chain systems in
experimental lung cancer.
Senthilnathan P, Padmavathi R, Magesh V, Sakthisekaran D.
Department of Medical Biochemistry, Dr. ALM Postgraduate Institute of Basic
Medical Sciences, University of Madras, Taramani, Chennai 600 113, India.
senthilnpm@rediffmail.com
The modulatory effect of Withania somnifera along with paclitaxel on
tricarboxylic acid (TCA) cycle key enzymes and electron transport chain
complexes were investigated against lung cancer induced by benzo(a)pyrene in
Swiss albino mice. Decreased activities of TCA cycle key enzymes such as
isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), malate
dehydrogenase (MDH) and alpha/ketoglutarate dehydrogenase (alpha/KGDH) in lung
cancer bearing animals were observed. Upon W. somnifera along with paclitaxel
administration the above biochemical changes were inclined towards normal
control animal values. Activities of mitochondrial enzymes and electron
transport complexes were analyzed in the experimental groups to determine the
efficiency of energy production. This study further confirms the
chemotherapeutic effect of W. somnifera along with paclitaxel which is found to
be more effective in the treatment of lung cancer. Thus these results are
consistent with our hypothesis that the combination chemotherapy of W. somnifera
along with paclitaxel as a promising chemotherapeutic agent.
PMID: 16143346 [PubMed / indexed for MEDLINE]
47: Biochem Biophys Res Commun. 2005 Aug 19;334(1):276/87.
Withanolides, a new class of natural cholinesterase inhibitors with calcium
antagonistic properties.
Choudhary MI, Nawaz SA, ul/Haq Z, Lodhi MA, Ghayur MN, Jalil S, Riaz N, Yousuf
S, Malik A, Gilani AH, ur/Rahman A.
Dr. Panjwani Center for Molecular Medicine and Drug Research, International
Center for Chemical Sciences, University of Karachi, Karachi/75270, Pakistan.
hej@cyber.net.pk
The withanolides 1/3 and 4/5 isolated from Ajuga bracteosa and Withania
somnifera, respectively, inhibited acetylcholinesterase (AChE, EC 3.1.1.7) and
butyrylcholinesterase (BChE, EC 3.1.1.8) enzymes in a concentration/dependent
fashion with IC50 values ranging between 20.5 and 49,2 microm and 29.0 and 85.2
microm for AChE and BChE, respectively. Lineweaver/Burk as well as Dixon plots
and their secondary replots indicated that compounds 1, 3, and 5 are the linear
mixed/type inhibitors of AChE, while 2 and 4 are non/competitive inhibitors of
AChE with K(i) values ranging between 20.0 and 45.0 microm. All compounds were
found to be non/competitive inhibitors of BChE with K(i) values ranging between
27.7 and 90.6 microm. Molecular docking study revealed that all the ligands are
completely buried inside the aromatic gorge of AChE, while compounds 1, 3, and 5
extend up to the catalytic triad. A comparison of the docking results showed
that all ligands generally adopt the same binding mode and lie parallel to the
surface of the gorge. The superposition of the docked structures demonstrated
that the non/flexible skeleton of the ligands always penetrates the aromatic
gorge through the six/membered ring A, allowing their simultaneous interaction
with more than one subsite of the active center. The affinity of ligands with
AChE was found to be the cumulative effects of number of hydrophobic contacts
and hydrogen bonding. Furthermore, all compounds also displayed dose/dependent
(0.005/1.0 mg/mL) spasmolytic and Ca2+ antagonistic potentials in isolated
rabbit jejunum preparations, compound 4 being the most active with an ED50 value
of 0.09 +// 0.001 mg/mL and 0.22 +// 0.01 microg/mL on spontaneous and K+
/induced contractions, respectively. The cholinesterase inhibitory potential
along with calcium antagonistic ability and safe profile in human neutrophil
viability assay could make compounds 1/5 possible drug candidates for further
study to treat Alzheimer's disease and associated problems.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 16108094 [PubMed / indexed for MEDLINE]
48: Phytother Res. 2005 May;19(5):409/15.
Effect of Dianex, a herbal formulation on experimentally induced diabetes
mellitus.
Mutalik S, Chetana M, Sulochana B, Devi PU, Udupa N.
College of Pharmaceutical Sciences, Manipal, Karnataka, India.
Dianex, a polyherbal formulation consisting of the aqueous extracts of Gymnema
sylvestre, Eugenia jambolana, Momordica charantia Azadirachta indica, Cassia
auriculata, Aegle marmelose, Withania somnifera and Curcuma longa was screened
for hypoglycemic activity in normal and streptozotocin induced diabetic mice.
Dianex was administered in different doses of 100/500 mg/kg/day orally in acute
(6 h) and long/term (6 weeks) studies. Blood glucose levels were checked 2/6 h
after treatment in acute studies and every 2 weeks in long/term studies. Body
weight was recorded on the first and final day of the treatment in the long/term
studies with diabetic mice. After 6 weeks, high/density lipoprotein,
triglycerides, total cholesterol, alanine transaminase (ALT), aspertate
transaminase (AST), urea and creatinine were estimated in serum of the diabetic
mice. Glycogen and total protein levels were estimated in the liver. Also, the
liver and pancreas was subjected to histological examination. Oral glucose
tolerance and in vitro free radical scavenging activity was also studied.Dianex
produced significant (p<0.05) hypoglycemic activity at 250/500 mg/kg doses in
both normal and diabetic mice in acute and long/term studies. The body weight of
diabetic mice significantly (p<0.05) increased with all tested doses of Dianex.
The elevated triglycerides, cholesterol, ALT, AST, urea and creatinine levels in
diabetic mice were significantly (p<0.05) reduced at the doses of 250 and 500
mg/kg. The liver glycogen and protein levels were both significantly (p<0.05)
increased in diabetic mice at 250 and 500 mg/kg doses. Dianex increased the
glucose tolerance significantly (p<0.05) in both normal and diabetic mice at all
the doses tested. Histopathological examination showed that the formulation
decreased streptozotocin induced injury to the tissues at all the doses tested.
It produced significant (p<0.05) free radical scavenging activity against ABTS+,
DPPH and hydroxyl free radicals at the concentrations ranging between 10/1000
microg/ml.Thus, in the present study, Dianex produced significant hypoglycemic
activity in both normal and diabetic animals. It also reversed other diabetic
complications in diabetic mice at 250 and 500 mg/kg doses. In our earlier study,
Dianex was well tolerated in laboratory animals at higher doses (upto 10 g/kg in
mice, acute toxicity; up to 2.5 g/kg in rats, subacute toxicity studies for 30
days) without exhibiting any toxic manifestation. Hence, Dianex may be useful in
the treatment of diabetes mellitus. Copyright (c) 2005 John Wiley & Sons, Ltd.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 16106394 [PubMed / indexed for MEDLINE]
49: Am J Clin Pathol. 2005 Aug;124(2):229/36.
Effect of Brazilian, Indian, Siberian, Asian, and North American ginseng on
serum digoxin measurement by immunoassays and binding of digoxin/like
immunoreactive components of ginseng with Fab fragment of antidigoxin antibody
(Digibind).
Dasgupta A, Reyes MA.
Department of Pathology and Laboratory Medicine, University of Texas/Houston
Medical School, 77030, USA.
We compared Brazilian, Indian, Siberian, Asian, and North American ginseng for
potential interference with 3 digoxin immunoassays: fluorescence polarization
(FPIA), microparticle enzyme (MEIA), and Tina/quant (Roche Diagnostics,
Indianapolis, IN). We supplemented aliquots of a drug/free serum pool with
ginseng extracts representing expected in vivo concentrations and overdose. We
observed apparent digoxin/like immunoreactivity with FPIA, modest
immunoreactivity with MEIA, and no apparent digoxin immunoreactivity with the
Tina/quant with all ginsengs except Brazilian, which showed no immunoreactivity
with any assay. When aliquots of serum pools prepared from patients receiving
digoxin were supplemented with ginsengs, we observed falsely elevated digoxin
values with FPIA, falsely lower digoxin values (negative interference) with
MEIA, and no interference with the Tina/quant. Digoxin/like immunoreactive
components of various ginsengs have moderate protein binding; monitoring free
digoxin concentrations does not eliminate such interference. We also observed
that Digibind (Burroughs Wellcome, Research Triangle Park, NC) can bind free
digoxin/like immunoreactive components of ginsengs; such effects can be
monitored by measuring apparent free digoxin concentrations. Indian, Asian, and
North American ginsengs interfere with serum digoxin measurement by FPIA and
MEIA; the Tina/quant is free of such interference. Digibind can bind free
digoxin/like immunoreactive components of ginseng.
Publication Types:
Comparative Study
PMID: 16040294 [PubMed / indexed for MEDLINE]
50: Nat Prod Res. 2005 Sep;19(6):567/71.
In vitro enzyme inhibition activities of crude ethanolic extracts derived from
medicinal plants of Pakistan.
Khattak S, Saeed/Ur/Rehman, Shah HU, Khan T, Ahmad M.
Department of Chemistry, University of Peshawar, Peshawar / 25120, Pakistan.
somiakhattak@yahoo.com
Twenty two crude ethanolic extracts from 14 indigenous medicinal plants were
subjected to enzyme inhibition screening against acetylcholinesterase (AChE),
butyrylcholinesterase (BChE) and lipoxygenase enzymes (LO). Three extracts
showed activity against AChE, nine extracts were found to be active against BChE
and four extracts inhibited the enzyme LO. The most significant inhibition
activities (> or =50%) were found in extracts derived from Aloe vera (leaves),
Alpinia galanga (rhizome), Curcuma longa (rhizome), Cymbopogon citratus
(leaves), Ocimum americanum (leaves), Ocimum americanum (stem) and Withania
somnifera (roots).
Publication Types:
In Vitro
PMID: 16010821 [PubMed / indexed for MEDLINE]
51: Phytomedicine. 2005 Jun;12(6/7):468/81.
Adaptogenic activity of glyco/peptido/lipid fraction from the alcoholic extract
of Trichopus zeylanicus Gaerten (part II).
Singh B, Chandan BK, Sharma N, Singh S, Khajuria A, Gupta DK.
Department of Pharmacology, Regional Research Laboratory, Canal Road,
Jammu//Tawi, India. bsjaggi2001@yahoo.com
Anti/stress activity was carried out on glyco/peptido/lipid (AF) fraction from
the alcoholic extract of Trichopus zeylanicus Gaerten and demonstrated against a
battery of tests in rats and mice. AF exhibited significant anti/stress activity
in dose/related manners in all the parameters studied against different models
used to induce non/specific stress viz physical and chemically. The major
parameters studied were immobilization induced gastric ulceration,
adjuvant/induced trauma (Stress); humoral antibody synthesis in normal and
immuno/suppressed mice and delayed type of hypersensitivity (DTH) reaction,
chemically stress/induced alteration in hepatic function and anti/oxidant
activity. The extract of Withania somnifera root (a commercial preparation
available locally, Dabur India ltd.) was used to compare the results. In the
safety evaluation study the maximum tolerance dose (MTD) and oral LD50 were
found to be more than 3000 mg/kg, with no signs of abnormalities or any
mortality observed for 15 days period under observation after single dose of
drug administration. Feeding behaviour and fecal output were normal.
PMID: 16008124 [PubMed / indexed for MEDLINE]
52: Indian J Med Res. 2005 May;121(5):683/90.
Influence of Yoga and Ayurveda on self/rated sleep in a geriatric population.
Manjunath NK, Telles S.
Swami Vivekananda Yoga Research Foundation, Bangalore, India.
BACKGROUND AND OBJECTIVE: Sleep in older persons is characterized by decreased
ability to stay asleep, resulting in fragmented sleep and reduced daytime
alertness. Pharmacological treatment of insomnia in older persons is associated
with hazardous side effects. Hence, the present study was designed to compare
the effects of Yoga and Ayurveda on the self rated sleep in a geriatric
population. METHODS: Of the 120 residents from a home for the aged, 69 were
stratified based on age (five year intervals) and randomly allocated to three
groups i.e., Yoga (physical postures, relaxation techniques, voluntarily
regulated breathing and lectures on yoga philosophy), Ayurveda (a herbal
preparation), and Wait/list control (no intervention). The groups were evaluated
for self/assessment of sleep over a one week period at baseline, and after three
and six months of the respective interventions. RESULTS: The Yoga group showed a
significant decrease in the time taken to fall asleep (approximate group average
decrease: 10 min, P<0.05), an increase in the total number of hours slept
(approximate group average increase: 60 min, P< 0.05) and in the feeling of
being rested in the morning based on a rating scale (P<0.05) after six months.
The other groups showed no significant change. INTERPRETATION AND CONCLUSION:
Yoga practice improved different aspects of sleep in a geriatric population.
Publication Types:
Clinical Trial
Comparative Study
Randomized Controlled Trial
Research Support, Non/U.S. Gov't
PMID: 15937373 [PubMed / indexed for MEDLINE]
53: Hum Exp Toxicol. 2005 Mar;24(3):137/47.
Neuroprotective effects of Withania somnifera on 6/hydroxydopamine induced
Parkinsonism in rats.
Ahmad M, Saleem S, Ahmad AS, Ansari MA, Yousuf S, Hoda MN, Islam F.
Neurotoxicology Laboratory, Department of Medical Elementology & Toxicology,
Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, India.
6/Hydroxydopamine (6/OHDA) is one of the most widely used rat models for
Parkinson's disease. There is ample evidence in the literature that 6/OHDA
elicits its toxic manifestations through oxidant stress. In the present study,
we evaluated the anti/parkinsonian effects of Withania somnifera extract, which
has been reported to have potent anti/oxidant, anti/peroxidative and free
radical quenching properties in various diseased conditions. Rats were
pretreated with 100, 200 and 300 mg/kg b.w. of the W. somnifera extract orally
for 3 weeks. On day 21, 2 microL of 6/OHDA (10 microg in 0.1% in ascorbic
acid/saline) was infused into the right striatum while sham operated group
received 2 microL of the vehicle. Three weeks after 6/OHDA injections, rats were
tested for neurobehavioral activity and were killed 5 weeks after lesioning for
the estimation of lipidperoxidation, reduced glutathione content, activities of
glutathione/S/transferase, glutathione reductase, gluta
