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Clinical Studies

Abstracts are presented below for clinical studies on Pepper.

  • Botanical Name: Piper Nigrum

  • Ayurvedic Name: Maricha

  • Common Name: Pepper

Piper Nigrum

Plant Phytonutrient Profile


1: Phytochemistry. 2006 Dec 21; [Epub ahead of print]

ACAT inhibition of alkamides identified in the fruits of Piper nigrum.

Rho MC, Lee SW, Park HR, Choi JH, Kang JY, Kim K, Lee HS, Kim YK.

Natural Medicine Research Center, Korea Research Institute of Bioscience and
Biotechnology, 52 Eoundong, Yusong/​gu, Daejon 305/​333, Republic of Korea.

In this study, via a bioactivity/​guided fractionation of MeOH extracts of the
fruits of Piper nigrum, alkamide (5) and five previously/​identified alkamides
were isolated. Their structures were elucidated via spectroscopic analysis
((1)H, (13)C NMR and ESI/​MS), as follows: retrofractamide A (1), pipercide (2),
piperchabamide D (3), pellitorin (4), dehydroretrofractamide C (5) and
dehydropipernonaline (6). The IC(50) values determined for the compounds were
24.5 (1), 3.7 (2), 13.5 (3), 40.5 (4), 60 (5) and 90muM (6), according to the
results of an ACAT enzyme assay system using rat liver microsomes. These
compounds all inhibited cholesterol esterification in HepG2 cells.

PMID: 17188313 [PubMed /​ as supplied by publisher]

2: J Agric Food Chem. 2006 Dec 27;54(26):9759/​63.

Inhibition of diacylglycerol acyltransferase by alkamides isolated from the
fruits of Piper longum and Piper nigrum.

Lee SW, Rho MC, Park HR, Choi JH, Kang JY, Lee JW, Kim K, Lee HS, Kim YK.

Natural Medicine Research Center, Korea Research Institute of Bioscience and
Biotechnology, Daejeon 305/​333, Korea, and School of Medicine, Pusan National
University, Pusan, Korea.

Pharmacological inhibition of acyl CoA:diacylglycerol acyltransferase (DGAT, EC
2.3.1.20) has emerged as a potential therapy for the treatment of obesity and
type 2 diabetes. Bioassay/​guided isolation of CHCl3 extracts of the fruits of
Piper longum and Piper nigum (Piperaceae), using an in vitro DGAT inhibitory
assay, lead to isolation of a new alkamide named
(2E,4Z,8E)/​N/​[9/​(3,4/​methylenedioxyphenyl)/​2,4,8/​nonatrienoyl]piperidine (2),
together with four known alkamides: retrofractamide C (1), pipernonaline (3),
piperrolein B (4), and dehydropipernonaline (5). Compounds 2/​5 inhibited DGAT
with IC50 values of 29.8 (2), 37.2 (3), 20.1 (4), and 21.2 (5) microM,
respectively, but the IC50 value for 1 was more than 900 microM. This finding
indicates that compounds possessing piperidine groups (2/​5) can be potential
DGAT inhibitors.

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

PMID: 17177498 [PubMed /​ in process]

3: Ying Yong Sheng Tai Xue Bao. 2006 Sep;17(9):1633/​6.

[Potential allelopathic effects of Piper nigrum, Mangifera indica and Clausena
lansium]

[Article in Chinese]

Yan G, Zhu C, Luo Y, Yang Y, Wei J.

College of Environment and Plant Protection, South China University of Tropical
Agriculture, Danzhou, China. yan_guijun@163.com

With Piper nigrum, Mangifera indica and Clausena lansium as the donators, this
paper studied their potential allelopathic effects on the germination and growth
of Zea mays, Glycine max, Cucurbita moschata, Arachis hypogaea, Raphanus
sativus, Echinochloa crusgalli, Digitaria sanguinalis and Stylosanthes
guianensis. The results showed that the aqueous extracts of these donators could
inhibit the germination and growth of Z. mays, G. max, C. moschata, E.
crus/​galli and D. sanguinalis at high concentration, but stimulate them at low
concentration. In rhizosphere soil of P. nigrum and M. indica, the germination
and growth of Z. mays L was stimulated, while A. hypogaea was inhibited. The
aqueous extracts of the donators were extracted by ethyl acetate and n/​butanol,
respectively, and the inhibitory activity of both aqueous and n/​butanol
fractions from P. nigrum and M. indica on Z. mays, R. sativus and S. guianensis
was stronger than that of ethyl acetate fraction, indicating that P. nigrum and
M. indica contained the allelochemicals with high polarity.

Publication Types:
English Abstract

PMID: 17147171 [PubMed /​ in process]

4: J Environ Sci Eng. 2005 Oct;47(4):276/​85.

Interaction of potassium phosphonate fungicide in laterite soil.

Kumar RA, Velayudhan KT, Vasu K, Ramachandran V, Bhai RS, Unnikrishnan G.

Isotope Hydrology Division, Centre for Water Resources Development and
Management, Kozhikode, Kerala, India.

Potassium phosphonate is a fungicide widely used to control Phytophthora fungi
species in many crops all over the world. In this paper, an attempt has been
made to study the interaction of potassium phosphonate with soil under varying
pH and calcium level. Several reports available in literature indicate that the
phosphonate in organic form adsorb strongly on almost all mineral surfaces and
natural materials like soil and sediments. The present study conducted on
laterite soil of Kerala using 2 mm sieved sample indicated that phosphonate
obeys Freundlich adsorption isotherm. Though at lower concentrations, Langmuir
model equally fits well, deviation was observed at higher concentrations. pH and
calcium content of the soil had striking influence on the interaction of the
chemical with the soil. The calcium source also appeared to influence the
adsorption phenomenon. Since potassium phosphonate is extensively used to
control Phytophthora fungi species in black pepper (Piper nigrum) plantations in
India and liming is a standard practice followed as soil amendment in acid soils
to increase the soil pH, this study may help to maintain good soil quality.

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

PMID: 17051913 [PubMed /​ indexed for MEDLINE]

5: Pak J Pharm Sci. 2006 Jul;19(3):214/​8.

Bactericidal activity of black pepper, bay leaf, aniseed and coriander against
oral isolates.

Chaudhry NM, Tariq P.

Department of Microbiology, University of Karachi, Karachi/​75270, Pakistan.

Present investigation focused on antibacterial potential of aqueous decoction of
black pepper (Piper nigrum L.), bay leaf (Laurus nobilis L.), aniseed
(Pimpinella anisum L.), and coriander (Coriandum sativum L.) against 176
bacterial isolates belonging to 12 different genera of bacterial population
isolated from oral cavity of 200 individuals. The disc diffusion technique was
employed. Overall aqueous decoction of black pepper was the most bacterial/​toxic
exhibited 75% antibacterial activity as compared to aqueous decoction of bay
leaf (53.4%) and aqueous decoction of aniseed (18.1%), at the concentration of
10 ml/disc. The aqueous decoction of coriander did not show any antibacterial
effect against tested bacterial isolates.

PMID: 16935829 [PubMed /​ indexed for MEDLINE]

6: Cell Biochem Funct. 2006 Nov/​Dec;24(6):491/​8.

Efficacy of piperine, an alkaloidal constituent from Piper nigrum on erythrocyte
antioxidant status in high fat diet and antithyroid drug induced hyperlipidemic
rats.

Vijayakumar RS, Nalini N.

Department of Biochemistry, Annamalai University, Annamalainagar/​608 002,
Tamilnadu, India.

The main aim of this study was to investigate the effect of piperine on
erythrocyte antioxidant status in high fat diet (HFD) and antithyroid drug
induced hyperlipidemic rats. Male Wistar rats were divided into eight groups.
The first four groups were fed a control diet and in addition were given
respectively 1% carboxymethyl cellulose (CMC); 10 mg/kg body weight carbimazole
(CM); 10 mg CM + 40 mg/kg body weight piperine and 10 mg CM + 2 mg/kg body
weight atorvastatin (ATV). A similar pattern was followed for the next four
groups except that they were all fed HFD instead of the control diet.
Erythrocyte osmotic fragility, total cholesterol, phospholipids, lipid
peroxidation products, enzymic and non/​enzymic antioxidant status were studied
in all experimental groups. Significantly increased osmotic fragility, total
cholesterol/phospholipid ratio, thiobarbituric acid reactive substances and
lipid hydroperoxides were observed in the plasma and erythrocytes of HFD fed and
CM treated rats compared to the control. Superoxide dismutase, catalase,
glutathione peroxidase, vitamin E and reduced glutathione in erythrocytes and
vitamin C in the plasma were also significantly lowered in HFD fed, antithyroid
drug treated rats compared to control animals. Concurrent piperine
supplementation along with HFD and antithyroid drug administration normalized
erythrocyte osmotic fragility, reduced lipid peroxidation, and improved the
enzymic and non/​enzymic antioxidant status compared to those rats that did not
receive piperine. Thus, our results indicate that piperine supplementation
markedly protects erythrocytes from oxidative stress by improving the
antioxidant status in HFD fed antithyroid drug treated rats. Copyright (c) 2006
John Wiley & Sons, Ltd.

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

PMID: 16927417 [PubMed /​ indexed for MEDLINE]

7: J Basic Clin Physiol Pharmacol. 2006;17(2):71/​86.

Piperine, an active principle from Piper nigrum, modulates hormonal and apo
lipoprotein profiles in hyperlipidemic rats.

Vijayakumar RS, Nalini N.

Department ofBiochemistry and Biotechnology, Annamalai University,
Annamalainagar/​608 002, Tamilnadu, India.

PURPOSE: To study the effect of piperine, an alkaloid, on thyroid hormones and
apolipoproteins in high/​fat/​diet (HFD) and antithyroid drug/​induced
hyperlipidemic rats. EXPERIMENTAL: Male Wistar rats were first divided into two
groups, control diet and high/​fat diet (HFD) and then subdivided into four
subgroups of ten animals each. The animals were treated with the following
regimens for 10 weeks: 1% carboxymethyl cellulose; 10 mg carbimazole (CM)/kg
body weight; 10 mg CM + 40 mg piperine/kg body weight, and 10 mg CM + 2 mg
atorvastatin /ATV//kg body weight. Lipid profiles, hormone levels, and
apolipoprotein levels were studied in all groups. RESULTS: HFD and/or CM
administration significantly elevated the plasma levels of total cholesterol,
VLDL, LDL, triglycerides, free fatty acids, and phospholipids, but significantly
reduced the HDL levels. Moreover, CM administration significantly reduced apo
A/​I levels and T3, T4 and testosterone levels while significantly elevating
plasma apo B, thyroid stimulating hormone (TSH) and insulin levels. The
simultaneous administration of piperine and HFD significantly reduced plasma
lipids and lipoproteins levels, except for HDL, which was significantly
elevated. Piperine supplementation also improved the plasma levels of apo A/​I,
T3, T4, testosterone, and I and significantly reduced apo B, TSH, and insulin to
near normal levels. CONCLUSIONS: The data presented here provide evidence that
piperine possesses thyrogenic activity, thus modulating apolipoprotein levels
and insulin resistance in HFD/​fed rats, opening a new view in the management of
dyslipidemia by dietary supplementation with nutrients.

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

PMID: 16910313 [PubMed /​ indexed for MEDLINE]

8: Ying Yong Sheng Tai Xue Bao. 2006 Apr;17(4):699/​702.

[Allelopathy of decomposing pepper stalk on pepper growth]

[Article in Chinese]

Hou Y, Zhou B, Wu X, Fu Y, Wang Y.

College of Horticulture, Shenyang Agricultural University, Shenyang 110161,
China. houyongxia@126.com

With decomposing pepper stalk as test material, this paper studied its
allelopathy on the growth of pepper plants. The results showed that after 60
days of decomposition, the decomposed pepper stalk could decrease the plant
height, stem diameter, dry weights of above/​and underground biomass, leaf area,
and chlorophyll content of pepper plants by 0.0374 /​ 0.0646, 0.0020 /​ 0.0097,
0.0050 /​ 0.0355 and 0.0916 /​ 0.3584, 0.0016 /​ 0.0251, and 0.0043 /​ 0.0242
respectively. These inhibitory effects were enhanced after 120 days of
decomposition, but the difference with CK was not significant. The root vigor
and its SOD, POD and CAT activities of pepper plants were decreased, while the
MDA content and relative conductivity were increased with the increasing
concentration of decomposed pepper stalk and with the prolong of treating time.
The allelopathic effects of decomposed pepper stalk on the physiological indices
of pepper root activity ranged from 0.0163 to 0.6507, which was significantly
higher than that of plant growth index.

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

PMID: 16836105 [PubMed /​ indexed for MEDLINE]

9: J Med Food. 2006 Summer;9(2):237/​45.

Effect of spices on lipid metabolism in 1,2/​dimethylhydrazine/​induced rat colon
carcinogenesis.

Nalini N, Manju V, Menon VP.

Department of Biochemistry, Annamalai University, Annamalainagar, Tamilnadu,
India. nalininam@yahoo.com

Colon cancer is the second most common cancer among men and women worldwide. We
investigated the effect of red chilli (Capsicum annum L.), cumin (Cuminum
cyminum L.), and black pepper (Piper nigrum L.) on colon cancer induced in rats
by a colon/​specific carcinogen, 1,2/​dimethylhydrazine (DMH). Colon cancer was
induced by subcutaneous injection of DMH at a dosage of 20 mg/kg of body weight
(15 doses, at 1/​week intervals). The rats were continued with the standard
pellet diet and supplemented red chilli [C. annum L., 0.015% (wt/wt) mixed with
the diet], cumin seeds [C. cyminum L., 1.25% (wt/wt) mixed with the diet], and
black pepper (P. nigrum L., 0.5% (wt/wt) mixed with the diet] throughout the
experimental period. After the total experimental period of 32 weeks (including
2 weeks of acclimatization) the incidence and number of tumors in the colon were
observed to be significantly higher in the rats administered DMH and/or red
chillis, as compared with the cumin + DMH and black pepper + DMH groups. No
tumors were observed in the control, cumin + DMH, or black pepper + DMH groups.
The levels of fecal bile acids and neutral sterols in 24/​hour fecal samples were
significantly decreased in DMH + chilli/​administered rats, while the excretion
of fecal bile acids and neutral sterols was significantly increased in cumin +
DMH/​ and black pepper + DMH/​administered rats. In DMH/​, chilli/​, and chilli +
DMH/​administered rats the levels of cholesterol, cholesterol/phospholipid ratio,
and 3/​hydroxy/​3/​methylglutaryl/​CoA reductase activity were decreased in cumin +
DMH/​ and black pepper + DMH/​treated rats. The phospholipid levels were reduced
in the DMH, chilli, and chilli + DMH groups as compared with the cumin + DMH and
black pepper + DMH groups. Our results show that chilli supplementation promotes
colon carcinogenesis, whereas cumin or black pepper suppresses colon
carcinogensis in the presence of the procarcinogen DMH.

PMID: 16822210 [PubMed /​ indexed for MEDLINE]

10: Planta Med. 2006 May;72(6):527/​32.

Mechanism/​based inhibition of human liver microsomal cytochrome P450 2D6
(CYP2D6) by alkamides of Piper nigrum.

Subehan, Usia T, Kadota S, Tezuka Y.

Institute of Natural Medicine, University of Toyama, Toyama, Japan.

Nineteen alkamides isolated from Piper nigrum L. were tested for their
mechanism/​based inhibition on human liver microsomal dextromethorphan
O/​demethylation activity, a prototype marker for cytochrome P450 2D6 (CYP2D6).
All compounds increased their inhibitory activity with increasing preincubation
time. Among them, 15 and 17 showed more than 50 % decrease of the CYP2D6
residual activity after 20 min preincubation. Further investigations on 15 and
17 showed that the characteristic time/​ and concentration/​dependent inhibition,
which required a catalytic step with NADPH, was not protected by nucleophiles,
and was decreased by the presence of a competitive inhibitor. The kinetic
parameters for inactivation (kinact and KI) were 0.028 min/​1 and 0.23 microM for
15 and 0.064 min/​1 and 0.71 microM for 17, respectively, which were stronger
than the known mechanism/​based inhibitor, paroxetine (a positive control). Thus,
15 and 17 are potent mechanism/​based inhibitors of CYP2D6.

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

PMID: 16808005 [PubMed /​ indexed for MEDLINE]

11: Biochem Pharmacol. 2006 Aug 14;72(4):486/​97. Epub 2006 Jun 14.

Modulation of cadmium induced alterations in murine thymocytes by piperine:
oxidative stress, apoptosis, phenotyping and blastogenesis.

Pathak N, Khandelwal S.

Industrial Toxicology Research Centre, Mahatma Gandhi Marg, P. Box 80, Lucknow
226001, India.

Piperine, a main component of Piper longum Linn. and Piper nigrum Linn., is a
plant alkaloid with a long history of medicinal use in Indian medicine. It is
known to exhibit a variety of biological activities which include anti/​pyretic,
anti/​inflammatory, anti/​depressant, hepatoprotective and antitumor. Its
immunomodulatory role has so far been limited to humoral response. The influence
of piperine on murine thymocytes, immunocompromised by cadmium has been reported
by us in this investigation. The various biochemical parameters such as
oxidative stress markers (ROS and GSH), Bcl/​2 protein expression, mitochondrial
membrane potential, caspase/​3 activity, DNA damage, blastogenesis and T
lymphocyte phenotypes were determined. Cadmium (25 microM) induced apoptosis
earliest at 6 h. Alterations in ROS and GSH preceded mitochondrial membrane
depolarization and caspase/​3 activation followed by apoptosis. The phenotypic
changes occurred at 18 h and blastogenesis at 72 h. Various conc. of piperine
(1, 10 and 50 microg/ml) when added along with Cd (25 microM) from 1.5 to 72 h,
caused a dose and time dependent amelioration in all the cellular events
mentioned above. Modulation of oxidative stress has earlier been reported to
reduce Cd induced apoptosis in murine lymphocytes. Inhibition of the ROS
production and replenishment of GSH by piperine, may in part be responsible for
the suppression of downstream cascade of events, i.e. apoptosis, blastogenesis
and T lymphocyte phenotyping. The study clearly demonstrated the anti/​oxidative,
anti/​apoptotic, and restorative ability against cell proliferative mitogenic
response and phenotypic alterations by piperine, suggesting its therapeutic
usefulness in immunocompromised conditions.

PMID: 16780805 [PubMed /​ indexed for MEDLINE]

12: Phytother Res. 2006 Aug;20(8):683/​6.

Effect of piperine on the steady/​state pharmacokinetics of phenytoin in patients
with epilepsy.

Pattanaik S, Hota D, Prabhakar S, Kharbanda P, Pandhi P.

Department of Pharmacology, Research Block B, Postgraduate Institute of Medical
Education and Research, Chandigarh 160012, India.

Piperine, the active principle of Piper longum, Piper nigrum and Zingiber
officinalis, has been reported to enhance the oral bioavailability of phenytoin
in human volunteers. The objective of this study was to explore the effect of a
single dose of piperine in patients with uncontrolled epilepsy on the
steady/​state pharmacokinetics of phenytoin. Two groups of 10 patients each
receiving either a 150 mg or 200 mg twice daily dose of phenytoin were selected.
Twelve hours after the night dose, venous blood samples were collected at 0,
0.5, 1, 2, 4, 6, 9, 12 h after administration of phenytoin. On the next study
day, piperine 20 mg was administered along with phenytoin and samples were
collected similarly. The mean plasma drug concentrations at different time
points and the pharmacokinetic parameters before and after piperine
administration were compared by Student's t/​test. Piperine increased
significantly the mean plasma concentration of phenytoin at most of the time
points in both dose groups. There was a significant increase in AUC((0/​12h)) (p
< 0.01), C(max) (p < 0.001) and K(a) (p < 0.05) whereas the changes in K(el) and
t(max) were not significant. The results showed that piperine enhanced the
bioavailability of phenytoin significantly, possibly by increasing the
absorption.

PMID: 16767797 [PubMed /​ indexed for MEDLINE]

13: Insect Mol Biol. 2006 Jun;15(3):329/​39.

Erratum in:
Insect Mol Biol. 2006 Dec;15(6):861.

The effect of a synergistic concentration of a Piper nigrum extract used in
conjunction with pyrethrum upon gene expression in Drosophila melanogaster.

Jensen HR, Scott IM, Sims SR, Trudeau VL, Arnason JT.

Department of Biology, University of Ottawa, Center for Advanced Research in
Environmental Genomics, Ottawa, Ontario, Canada.

An ethyl acetate extract of Piper nigrum L. (Piperaceae) peppercorns was tested
as a synergist for the botanical insecticide pyrethrum. A high synergist ratio
of 11.6 against Drosophila melanogaster was obtained for the combination of
pyrethrum supplemented with P. nigrum. The effect of this combination was
investigated using cDNA microarray analysis of gene expression profiles in D.
melanogaster. Treatment of D. melanogaster with pyrethrum alone resulted in a
large number of differentially expressed genes, principally associated with
stress responses. Seven genes were identified as being commonly expressed in D.
melanogaster treated with at least two of the following treatments: P. nigrum,
pyrethrum or P. nigrum plus pyrethrum. These are likely implicated in Drosophila
defence responses to toxins.

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

PMID: 16756552 [PubMed /​ indexed for MEDLINE]

14: Int J Food Sci Nutr. 2005 Nov;56(7):491/​9.

The antioxidant and radical scavenging activities of black pepper (Piper nigrum)
seeds.

Gulcin I.

Department of Chemistry, Ataturk University, Faculty of Science and Arts,
TR/​25240, Erzurum, Turkey. igulcin@atauni.edu.tr

Water and ethanol crude extracts from black pepper (Piper nigrum) were
investigated for their antioxidant and radical scavenging activities in six
different assay, namely, total antioxidant activity, reducing power,
1,1/​Diphenyl/​2/​picryl/​hydrazyl (DPPH) free radical scavenging, superoxide anion
radical scavenging, hydrogen peroxide scavenging, and metal chelating
activities. Both water extract (WEBP) and ethanol extract (EEBP) of black pepper
exhibited strong total antioxidant activity. The 75 microg/ml concentration of
WEBP and EEBP showed 95.5% and 93.3% inhibition on peroxidation of linoleic acid
emulsion, respectively. On the other hand, at the same concentration, standard
antioxidants such as butylated hydroxyanisole (BHA), butylated hydroxytoluene
(BHT) and alpha/​tocopherol exhibited 92.1%, 95.0%, and 70.4% inhibition on
peroxidation of linoleic acid emulsion, respectively. Also, total phenolic
content in both WEBP and EEBP were determined as gallic acid equivalents. The
total phenolics content of water and ethanol extracts were determined by the
Folin/​Ciocalteu procedure and 54.3 and 42.8 microg gallic acid equivalent of
phenols was detected in 1 mg WEBP and EEBP.

PMID: 16503560 [PubMed /​ indexed for MEDLINE]

15: Spectrochim Acta A Mol Biomol Spectrosc. 2006 Mar 13;63(4):879/​82. Epub 2006
Feb 21.

An ESR protocol based on relaxation phenomena of irradiated Japanese pepper.

Ukai M, Nakamura H, Shimoyama Y.

Department of Food Science, Hokkaido University of Education, Hakodate 040/​8567,
Japan. mitsuko@cc.hokkyodai.ac.jp

We found various free radicals in a commercially available pepper in Japan
before and after irradiation using electron spin resonance (ESR) spectroscopy.
The typical ESR spectrum of the pepper consists of a sextet centered at g = 2.0,
a singlet at the same g/​value and a singlet at g = 4.0. Upon gamma ray
irradiation, a new pair of signals appeared in the pepper. The progressive
saturation behavior (PSB) at various microwave power levels indicated quite
different relaxation behaviors of those radicals. Namely, the peak intensity of
the organic free radical component decreases in a monotonic fashion, whereas the
Mn2+ and Fe3+ ESR signals substantially keep constant. This reflects the
evidence of three independent radicals in the pepper before irradiation. The PSB
of the pair peaks as induced by irradiation possessed quite different PSB from
that of the free radical located at g = 2.0. We proposed a new protocol for the
ESR detection of irradiated foods by the PSB method at different microwave power
levels. This would call for a major modification of the CEN protocol in European
Union.

PMID: 16495128 [PubMed /​ indexed for MEDLINE]

16: J Agric Food Chem. 2006 Feb 22;54(4):1289/​95.

Gene expression profiles of Drosophila melanogaster exposed to an insecticidal
extract of Piper nigrum.

Jensen HR, Scott IM, Sims S, Trudeau VL, Arnason JT.

Department of Biology, University of Ottawa, Ottawa/​Carleton Institute of
Biology, 30 Marie/​Curie Street, Ottawa, Ontario K1N 6N5, Canada.

Black pepper, Piper nigrum L. (Piperaceae), has insecticidal properties and
could potentially be utilized as an alternative to synthetic insecticides.
Piperine extracted from P. nigrum has a biphasic effect upon cytochrome P450
monooxygenase activity with an initial suppression followed by induction. In
this study, an ethyl acetate extract of P. nigrum seeds was tested for
insecticidal activity toward adult Musca domestica and Drosophila melanogaster.
The effect of this same P. nigrum extract upon differential gene expression in
D. melanogaster was investigated using cDNA microarray analysis of 7380 genes.
Treatment of D. melanogaster with P. nigrum extract led to a greater than 2/​fold
upregulation of transcription of the cytochrome P450 phase I metabolism genes
Cyp 6a8, Cyp 9b2, and Cyp 12d1 as well as the glutathione/​S/​transferase phase II
metabolism gene Gst/​S1. These data suggests a complex effect of P. nigrum upon
toxin metabolism.

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

PMID: 16478250 [PubMed /​ indexed for MEDLINE]

17: J Ethnopharmacol. 2006 May 24;105(3):449/​55. Epub 2006 Jan 18.

Mechanism/​based inhibition of CYP3A4 and CYP2D6 by Indonesian medicinal plants.

Subehan, Usia T, Iwata H, Kadota S, Tezuka Y.

Institute of Natural Medicine, Toyama Medical and Pharmaceutical University,
2630/​Sugitani, Toyama 930/​0194, Japan.

Thirty samples of Indonesian medicinal plants were tested for their
mechanism/​based inhibition on cytochrome P450 3A4 (CYP3A4) and CYP2D6 via
erythromycin N/​demethylation and dextromethorphan O/​demethylation activities in
human liver microsomes. From screening with 0 and 20min preincubation at
0.5mg/ml of methanol extracts, five plants (Cinnamomum burmani bark, Foeniculum
vulgare seed, Strychnos ligustrina wood, Tinospora crispa stem, and Zingiber
cassumunar rhizome) showed more than 30% increase of CYP3A4 inhibition, while
three (Alpinia galanga rhizome, Melaleuca leucadendron leaf, and Piper nigrum
fruit) showed more than 30% increase of CYP2D6 inhibition. In these eight
plants, Foeniculum vulgare seed, Cinnamomum burmani bark, and Strychnos
ligustrina wood showed time/​dependent inhibition on CYP3A4 and Piper nigrum
fruit and Melaleuca leucadendron leaf on CYP2D6. Among these, four plants other
than Melaleuca leucadendron revealed NADPH/​dependent inhibition. Thus,
Foeniculum vulgare, Cinnamomum burmani, and Strychnos ligustrina should contain
mechanism/​based inhibitors on CYP3A4 and Piper nigrum contain that on CYP2D6.

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

PMID: 16414224 [PubMed /​ indexed for MEDLINE]

18: Phytomedicine. 2006 Jan;13(1/​2):67/​73. Epub 2005 Jun 29.

CYP3A4 and CYP2D6 inhibitory activities of Indonesian medicinal plants.

Usia T, Iwata H, Hiratsuka A, Watabe T, Kadota S, Tezuka Y.

Institute of Natural Medicine, Toyama Medical and Pharmaceutical University,
2630/​Sugitani, Toyama 930/​0194, Japan.

Thirty samples of Indonesian medicinal plants were analyzed for their capacity
to inhibit in vitro metabolism by human cytochrome P450 3A4 (CYP3A4) and CYP2D6
with a radiometric assay. The MeOH/​soluble fractions of 25 samples, prepared
from water extracts, demonstrated inhibitory activity more than 50% on the
metabolism mediated by CYP3A4, and 21 samples on the metabolism mediated by
CYP2D6. Among the MeOH/​soluble fractions, Piper nigrum leaf showed the highest
inhibitory activity against CYP3A4 (91.7%), and Punica granatum against CYP2D6
(98.1%). The water extracts of which MeOH/​soluble fraction showed inhibitory
activity more than 70% were fractionated with EtOAc. From the EtOAc/​soluble
fractions, Curcuma heyneana (67.0%), Pi. cubeba (75.0%), Pi. nigrum fruit
(84.0%), Pi. nigrum leaf (85.8%), and Zingiber aromaticum (75.3%) demonstrated
inhibitory activity more than 50% on the metabolism mediated by CYP3A4, but only
Pi. nigrum fruit (72.8%) and Pi. nigrum leaf (69.1%) showed strong inhibitory
activity against CYP2D6. For samples that showed more than 70% inhibition, their
IC(50) values were determined. The most potent inhibitory activity against
CYP3A4 (IC(50) value of 25 microg/ml) was found for the extract of Pi. nigrum
leaf, while that of Catharanthus roseus showed the most potent inhibitory effect
against CYP2D6 (IC(50) value of 11 microg/ml). These results should indicate
once more the possibility of potential medicinal plant/​drug interactions.

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

PMID: 16360935 [PubMed /​ indexed for MEDLINE]

19: J Ethnopharmacol. 2006 Apr 21;105(1/​2):76/​83. Epub 2005 Dec 6.

Antioxidant activity of a salt/​spice/​herbal mixture against free radical
induction.

Natarajan KS, Narasimhan M, Shanmugasundaram KR, Shanmugasundaram ER.

ALMPG Institute of Basic Medical Sciences, University of Madras, Taramani
Campus, Chennai 600113, India.

A combination of spices (Piper nigrum, Piper longum and Zingiber officinale),
herbs (Cyperus rotundus and Plumbago zeylanica) and salts make up Amrita Bindu.
The study was focused to evaluate the antioxidant property of individual
ingredients in Amrita Bindu against the free radical
2,2'/​azinobis/​(3/​ethylbenzothiazoline/​6/​sulphonic acid) (ABTS). The analysis
revealed the antioxidant potential of the ingredients in the following order:
Piper nigrum>Piper longum>Cyperus rotundus>Plumbago zeylanca>Zingiber
officinale. Two different experiments were designed. In experiment I, rats were
fed with normal diet whereas in experiment II rats were given feed mixed with
Amrita Bindu for 3 weeks (4 g/kg of feed). Rats from both experimental groups
were challenged against a single intraperitonial injection of phenylhydrazine
(PHZ) (7.5 mg/kg body weight). At the end of 24 and 72 h, blood was analysed for
free radicals and antioxidant levels. It was interesting to note that rats with
Amrita Bindu pretreatment showed significantly lower levels of free radicals,
lipid peroxidation and protein carbonyls along with significantly higher levels
of antioxidants when compared with rats without Amrita Bindu pretreatment on PHZ
administration. These results reveal that Amrita Bindu, a salt/​spice/​herbal
mixture exerts a promising antioxidant potential against free radical induced
oxidative damage.

PMID: 16337350 [PubMed /​ indexed for MEDLINE]

20: Plant Cell Rep. 2006 Jan;24(12):699/​707. Epub 2005 Oct 25.

High/​frequency plant regeneration through cyclic secondary somatic embryogenesis
in black pepper (Piper nigrum L.).

Nair RR, Dutta Gupta S.

Indian Institute of Spices Research, Calicut, 673012, Kerala, India.
rrnair9@rediffmail.com

A high/​frequency plantlet regeneration protocol was developed for black pepper
(Piper nigrum L.) through cyclic secondary somatic embryogenesis. Secondary
embryos formed from the radicular end of the primary somatic embryos which were
originally derived from micropylar tissues of germinating seeds on growth
regulator/​free SH medium in the absence of light. The process of secondary
embryogenesis continued in a cyclic manner from the root pole of newly formed
embryos resulting in clumps of somatic embryos. Strength of the medium and
sucrose concentration influenced the process of secondary embryogenesis and
fresh weight of somatic embryo clumps. Full/​strength SH medium supplemented with
1.5% sucrose produced significantly higher fresh weight and numbers of secondary
somatic embryos while 3.0 and 4.5% sucrose in the medium favored further
development of proliferated embryos into plantlets. Ontogeny of secondary
embryos was established by histological analysis. Secondary embryogenic
potential was influenced by the developmental stage of the explanted somatic
embryo and stages up to "torpedo" were more suitable. A single/​flask system was
standardized for proliferation, maturation, germination and conversion of
secondary somatic embryos in suspension cultures. The system of cyclic secondary
somatic embryogenesis in black pepper described here represents a permanent
source of embryogenic material that can be used for genetic manipulations of
this crop species.

PMID: 16249871 [PubMed /​ indexed for MEDLINE]

21: Nat Prod Res. 2005 Oct;19(7):703/​12.

Phytochemical studies on the seed extract of Piper nigrum Linn.

Rasheed M, Afshan F, Tariq RM, Siddiqui BS, Gulzar T, Mahmood A, Begum S, Khan
B.

H.E.J. Research institute of Chemistry, International Centre for Chemical
Sciences, University of Karachi, Karachi/​75270, Pakistan.
bina@khi.comsats.net.pk

The petroleum ether extract of dried ground seeds of Piper nigrum Linn. and some
column fractions of this extract were subjected to GC and GC/​MS analysis,
resulting in the identification of fourteen compounds (1/​14) by using NIST Mass
spectral search program 1998 and the Kovat's retention indices. Ten of the
compounds (1, 2, 4/​12) are reported for the first time from this plant. All the
fractions showed insecticidal activity against the fourth instar larvae of Aedes
aegypti and against the fourth instar larvae of Anopheles stephensi Liston,
determined by the WHO method.

PMID: 16076642 [PubMed /​ indexed for MEDLINE]

22: J Agric Food Chem. 2005 Jul 27;53(15):6056/​60.

Role of the fermentation process in off/​odorant formation in white pepper:
on/​site trial in Thailand.

Steinhaus M, Schieberle P.

Deutsche Forschungsanstalt fur Lebensmittelchemie, Lichtenbergstrasse 4, D/​85748
Garching, Germany.

In white pepper samples, directly taken from a retting batch at a pepper
production plant in Thailand, 3/​methylindole, 4/​methylphenol, 3/​methylphenol,
and butanoic acid, recently confirmed to be responsible for the characteristic
fecal off/​odor frequently detected in white pepper powders, were quantified by
stable isotope dilution analyses. The results clearly showed that, in
particular, 3/​methylindole (fecal, swine/​manure/​like), 4/​methylphenol (fecal,
horse/​like), and butanoic acid (cheese/​like) were biochemically formed during
retting, thus indicating that fermentation is the crucial step for off/​odorant
formation during white pepper processing. Model fermentation experiments
performed with different manufacturing regimens revealed that white pepper,
containing no substantial amounts of these odorants, can be produced from ripe
starting material by a short fermentation under water and with frequent exchange
of water. The overall aroma of such pepper was superior as compared to the aroma
of white pepper produced according to the traditional procedure.

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

PMID: 16028995 [PubMed /​ indexed for MEDLINE]

23: J Agric Food Chem. 2005 Jul 27;53(15):6049/​55.

Characterization of odorants causing an atypical aroma in white pepper powder
(Piper nigrum L.) based on quantitative measurements and orthonasal breakthrough
thresholds.

Steinhaus M, Schieberle P.

Deutsche Forschungsanstalt fur Lebensmittelchemie, Lichtenbergstrasse 4, D/​85748
Garching, Germany.

Application of the aroma extract dilution analysis on an extract of white pepper
powder showing an intense fecal, cowshed/​like off/​flavor revealed 3/​methylindole
(fecal, swine/​manure) and 4/​methylphenol (fecal, horse/​like) with the highest
flavor dilution (FD) factors among the 22 odor/​active compounds detected. In
addition, high FD factors and/or undesirable odor qualities suggested
3/​methylphenol (phenolic), butanoic acid (cheese/​like), and 2/​ and
3/​methylbutanoic acid (cheese/​like) as well as pentanoic acid and hexanoic acid
(cheese/​like odors) as contributors to the malodor. Although the intensities of
the off/​note were clearly different in 50 commercial samples of white pepper,
quantitation of 3/​methylindole and 3/​ and 4/​methylphenol as well as of the five
short/​chain acids by means of stable isotope dilution assays showed similar
concentrations in most of the samples. Storage of a freshly ground white pepper
powder for up to 7 months revealed a significant decrease in the typical odor
qualities of white pepper and an increase in the fecal odor note with storage
time. Because the concentrations of the odorants mentioned above were not much
changed during storage, possibly very volatile odorants, such as alpha/​pinene,
which are able to mask the malodor, are lost during storage of, in particular,
pepper powders. On the basis of odor activity values, which were calculated
using breakthrough thresholds, in particular, 3/​methylindole, 4/​methylphenol,
3/​methylphenol, and butanoic acid could be suggested as the main sources of the
fecal off/​flavor.

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

PMID: 16028994 [PubMed /​ indexed for MEDLINE]

24: J Econ Entomol. 2005 Jun;98(3):845/​55.

Efficacy of botanical insecticides from Piper species (Piperaceae) extracts for
control of Ruropean chafer (Coleoptera: Scarabaeidae).

Scott IM, Gagnon N, Lesage L, Philogene BJ, Arnason JT.

Department of Biology, University of Ottawa, Ottawa, ON, K1N 6N5, Canada.

Biopesticides, including botanicals, can offer a safe and effective alternative
to conventional insecticides for controlling major insect pests within an
integrated pest management program. The current study highlights the practical
application of a botanical insecticide for controlling a major insect pest of
turfgrass: European chafer, Rhizotrogus majalis (Razoumowsky). Greenhouse and
field trials were conducted to test the efficacy of a botanical formulation
based on black pepper, Piper nigrum L. (Piperaceae), seed extracts to R. majalis
larvae. The 7/​d P. nigrum extract LC50 for R. majalis third instars was 2.5%.
Successful treatment in the field was accomplished with the application of a 2%
P. nigrum formulation to turfgrass infested with R. majalis second and third
instars, whereas 4% extract was required in a second field trial with older
third instars. The 2% pepper extract activity was comparable with the
conventional insecticide diazinon in the first field trial. However, the 4%
pepper extracts significantly affected the earthworm populations in treated
plots compared with diazinon in the second field trail. The analysis of soil
residues for piperamides in the P. nigrum extract determined a half/​life of 1 /​
2.6 d in the first and second field trials, respectively. This confirmed the
expectation that under field conditions the residual activity would be less than
conventional insecticides, thereby reducing the environmental risk associated
with pesticide use. We recommend the pepper formulation for spot treatment
applications when population densities reveal an epicenter of infestation rather
than broadcasting over large areas, thus helping to minimize cost and negative
affects on nontarget invertebrates.

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

PMID: 16022313 [PubMed /​ indexed for MEDLINE]

25: Org Lett. 2005 Jul 7;7(14):2833/​5.

Cobalt(II)/​catalyzed intermolecular Diels/​Alder reaction of piperine.

Wei K, Li W, Koike K, Nikaido T.

Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Chiba.

[reaction: see text] An intermolecular cobalt/​phosphine/​catalyzed Diels/​Alder
reaction of piperine is described. The dimerization of piperine in the presence
of cobalt/​phosphine complexes gave much better yields than that in the presence
of only cobalt, which, combined with the result under the purely thermal
conditions, indicates that addition of phosphine ligands changes the inhibition
of cobalt to the reaction into promotion. For elucidation of the distinction,
different cobalt/​catalyzed mechanisms were proposed for the Diels/​Alder
dimerization of piperine.

PMID: 15987148 [PubMed /​ indexed for MEDLINE]

26: Pulm Pharmacol Ther. 2006;19(2):107/​11. Epub 2005 Jun 21.

In vivo effect of piperine on serum and tissue glycoprotein levels in
benzo(a)pyrene induced lung carcinogenesis in Swiss albino mice.

Selvendiran K, Prince Vijeya Singh J, Sakthisekaran D.

Department of Medical Biochemistry, Dr ALM Post Graduate Institute of Basic
Medical Sciences, University of Madras, Taramani Campus, Chennai, India.
selvakphd@yahoo.com

In recent years, considerable emphasis has been focused on identifying new
cancer chemopreventive agents, which could be useful for the human population.
Piperine is a pure, pungent alkaloid constituent of black and long peppers
(Piper nigrum and Piper longum), that acts as an antioxidant and anticancer
agent by its numerous macromolecules associated with them. In the present study,
piperine was found to suppress benzo(a)pyrene (B(a)p) induced lung cancer in
Swiss albino mice. In lung cancer bearing mice, altered levels of total protein
and protein bound carbohydrate components (hexose, hexosamine and sialic acid)
were observed in serum, lung and liver tissues. Dietary supplementation of
piperine (50 mg/kg body weight) to B(a)p administered animals decreased the
total protein and protein bound carbohydrate levels of lung cancer bearing
animals in during initiation and post/​initiation phases. Our data suggest that
piperine may extend its chemopreventive effect through modulating the protein
bound carbohydrate levels, as they are one of the indicators of tumorigenesis.

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

PMID: 15975841 [PubMed /​ indexed for MEDLINE]

27: Drugs. 2005;65(9):1239/​82.

Herb/​drug interactions: a literature review.

Hu Z, Yang X, Ho PC, Chan SY, Heng PW, Chan E, Duan W, Koh HL, Zhou S.

Department of Pharmacy, Faculty of Science, National University of Singapore,
Singapore.

Herbs are often administered in combination with therapeutic drugs, raising the
potential of herb/​drug interactions. An extensive review of the literature
identified reported herb/​drug interactions with clinical significance, many of
which are from case reports and limited clinical observations.Cases have been
published reporting enhanced anticoagulation and bleeding when patients on
long/​term warfarin therapy also took Salvia miltiorrhiza (danshen). Allium
sativum (garlic) decreased the area under the plasma concentration/​time curve
(AUC) and maximum plasma concentration of saquinavir, but not ritonavir and
paracetamol (acetaminophen), in volunteers. A. sativum increased the clotting
time and international normalised ratio of warfarin and caused hypoglycaemia
when taken with chlorpropamide. Ginkgo biloba (ginkgo) caused bleeding when
combined with warfarin or aspirin (acetylsalicylic acid), raised blood pressure
when combined with a thiazide diuretic and even caused coma when combined with
trazodone in patients. Panax ginseng (ginseng) reduced the blood concentrations
of alcohol (ethanol) and warfarin, and induced mania when used concomitantly
with phenelzine, but ginseng increased the efficacy of influenza vaccination.
Scutellaria baicalensis (huangqin) ameliorated irinotecan/​induced
gastrointestinal toxicity in cancer patients.Piper methysticum (kava) increased
the 'off' periods in patients with parkinsonism taking levodopa and induced a
semicomatose state when given concomitantly with alprazolam. Kava enhanced the
hypnotic effect of alcohol in mice, but this was not observed in humans. Silybum
marianum (milk thistle) decreased the trough concentrations of indinavir in
humans. Piperine from black (Piper nigrum Linn) and long (P. longum Linn)
peppers increased the AUC of phenytoin, propranolol and theophylline in healthy
volunteers and plasma concentrations of rifamipicin (rifampin) in patients with
pulmonary tuberculosis. Eleutheroccus senticosus (Siberian ginseng) increased
the serum concentration of digoxin, but did not alter the pharmacokinetics of
dextromethorphan and alprazolam in humans. Hypericum perforatum (hypericum; St
John's wort) decreased the blood concentrations of ciclosporin (cyclosporin),
midazolam, tacrolimus, amitriptyline, digoxin, indinavir, warfarin,
phenprocoumon and theophylline, but did not alter the pharmacokinetics of
carbamazepine, pravastatin, mycophenolate mofetil and dextromethorphan. Cases
have been reported where decreased ciclosporin concentrations led to organ
rejection. Hypericum also caused breakthrough bleeding and unplanned pregnancies
when used concomitantly with oral contraceptives. It also caused serotonin
syndrome when used in combination with selective serotonin reuptake inhibitors
(e.g. sertraline and paroxetine).In conclusion, interactions between herbal
medicines and prescribed drugs can occur and may lead to serious clinical
consequences. There are other theoretical interactions indicated by preclinical
data. Both pharmacokinetic and/or pharmacodynamic mechanisms have been
considered to play a role in these interactions, although the underlying
mechanisms for the altered drug effects and/or concentrations by concomitant
herbal medicines are yet to be determined. The clinical importance of herb/​drug
interactions depends on many factors associated with the particular herb, drug
and patient. Herbs should be appropriately labeled to alert consumers to
potential interactions when concomitantly used with drugs, and to recommend a
consultation with their general practitioners and other medical carers.

Publication Types:
Review

PMID: 15916450 [PubMed /​ indexed for MEDLINE]

28: Indian J Physiol Pharmacol. 2005 Jan;49(1):65/​71.

Protective effects of Piper nigrum and Vinca rosea in alloxan induced diabetic
rats.

Kaleem M, Sheema, Sarmad H, Bano B.

Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh /​ 202 002.
kaleem_biochem@yahoo.com

In the present study aqueous extract of Piper nigrum seeds and Vinca rosea
flowers were administered orally to alloxan induced diabetic rats once a day for
4 weeks. These treatments lead to significant lowering of blood sugar level and
reduction in serum lipids. The levels of antioxidant enzymes, catalase and
glutathione peroxidase decreased in alloxan induced diabetic rats however these
levels returned to normal in insulin, P. nigrum and V. rosea treated rats. There
was no significant difference in superoxide dismutase activity in all groups
compared to controls. Lipid peroxidation levels were significantly higher in
diabetic rats and it was slightly increased in insulin, P. nigrum and V. rosea
treated rats as compared to control rat. These results suggest that oxidative
stress plays a key role in diabetes, and treatment with P. nigrum and V. rosea
are useful in controlling not only the glucose and lipid levels but these
components may also be helpful in strengthening the antioxidants potential.

Publication Types:
Comparative Study

PMID: 15881860 [PubMed /​ indexed for MEDLINE]

29: Mol Cell Biochem. 2005 Mar;271(1/​2):101/​6.

Chemopreventive effect of piperine on mitochondrial TCA cycle and phase/​I and
glutathione/​metabolizing enzymes in benzo(a)pyrene induced lung carcinogenesis
in Swiss albino mice.

Selvendiran K, Thirunavukkarasu C, Singh JP, Padmavathi R, Sakthisekaran D.

Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic
Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India.
selvakphd@yahoo.com

Piperine is a major component of black (Piper nigrum Linn) and long pepper
(Piper longum Linn) used widely in various systems of traditional medicine. We
have evaluated the effect of piperine on mitochondrial tricarboxylic acid cycle
and phase I and glutathione/​metabolizing enzymes in Benzo(a)pyrene induced
experimental lung carcinogenesis in swiss albino mice. Lung cancer bearing mice
showed a significant decrease in the activities of mitochondrial
enzymes/​isocitrate dehydrogenase (ICDH), /​ketoglutarate dehydrogenase (KDH),
succinate dehydrogenase (SDH), malate dehydrogenase (MDH) and significantly
increased NADPH/​Cytochorome reductase (NADPH/​C reductase), cytochrome P450
(cyt/​p450) and cytochrome b5(cyt/​b5). The activities of glutathione/​metabolizing
enzymes glutathione peroxidase(GPx), glutathione reductase (GR) and
glucose/​6/​phospho dehydrogenase(G6PDH) were significantly lowered in lung/​cancer
bearing mice when compared with control mice. Piperine supplementation to
tumour/​induced animals significantly lowered the phase/​I enzymes (NADPH/​C
reductase, cyt/​p450 and cyt/​b5)) and there was a rise in
glutathione/​metabolizing enzymes (GPx, GR and G6PDH), which indicated an
antitumour and anti/​cancer effect. Comparison of normal control mice and mice
administered piperine only as drug control showed no significant variations in
enzyme activities. Piprine administration to benzo(a)pyrene induced animals
significantly increased the activities of mitochondrial enzymes, thereby
suggesting its role in mitochondrial energy production.

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

PMID: 15881660 [PubMed /​ indexed for MEDLINE]

30: J Agric Food Chem. 2005 Mar 23;53(6):1907/​13.

Analysis of Piperaceae germplasm by HPLC and LCMS: a method for isolating and
identifying unsaturated amides from Piper spp extracts.

Scott IM, Puniani E, Jensen H, Livesey JF, Poveda L, Sanchez/​Vindas P, Durst T,
Arnason JT.

Biology Department, University of Ottawa, Ottawa, Ontario, K1N 6N5, Canada.
iscott@science.uottawa.ca

A method for extraction and high performance liquid chromatography/​mass
spectrometer (HPLC/​MS) analysis of the medicinally important genus Piper
(Piperaceae) was developed. This allows for a rapid and accurate measure of
unsaturated amides, or piperamides, in black pepper, Piper nigrum L., and in
wild species from Central America. Reflux extraction provided the highest
recovery of piperine (>80%) from leaf and peppercorn material. HPLC analysis
using a binary gradient of acetonitrile and water separated the major amide
peaks between 5 and 12 min. Atmospheric pressure chemical ionization (APCI)/​MS
improved the detection limit to 0.2 ng, 10/​fold below the 2 ng limit of the
HPLC/​diode array detector (DAD) based on linear standard curves between 0.1 and
250 microg/mL (R2 = 0.999). The HPLC/​MS method identified pellitorine,
piperylin, 4,5/​dihydropiperlonguminine, piperlonguminine, 4,5/​dihydropiperine,
piperine, and pipercide. The biological activity of six Costa Rican Piper
species assessed by mosquito larval bioassays correlated well with piperamide
content.

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

PMID: 15769112 [PubMed /​ indexed for MEDLINE]

31: Phytother Res. 2004 Dec;18(12):976/​81.

Effect of an indigenous herbal compound preparation 'Trikatu' on the lipid
profiles of atherogenic diet and standard diet fed Rattus norvegicus.

Sivakumar V, Sivakumar S.

Department of Zoology, Annamalai University, Annamalai nagar, 608002 Tamil Nadu,
India. drvalsacdm@yahoo.co.in

Combating heart disease is one of the challenging problems of biomedical science
today. Towards this goal an indigenous preparation 'Trikatu' (a herbal
combination containing Piper longum (fruit), Piper nigrum (fruit) and Zingiber
officinale (rhizome) dry powder) was fed to normal and cholesterol fed male
Rattus norvegicus to ascertain its efficacy as a hypolipidaemic agent. Its
effects on body weight, blood and tissue (aortic, cardiac and hepatic)
lipids/​/​total, free and esterified cholesterol, low density lipoprotein(LDL) and
high density lipoprotein(HDL) cholesterol, triglycerides and phospholipids/​/​and
the atherogenic index were measured. It was found that 'Trikatu' by virtue of
its ability to reduce triglycerides and LDL cholesterol and to increase HDL
cholesterol can reduce the risk of hyperlipidaemia and atherosclerosis. Hence
'Trikatu' can be used as a potent hypolipidaemic agent and it can reduce the
atherosclerosis associated with a high fat diet. 2004 John Wiley & Sons, Ltd.

PMID: 15742354 [PubMed /​ indexed for MEDLINE]

32: Mol Cell Biochem. 2005 Jan;268(1/​2):141/​7.

Oral supplementation of piperine leads to altered phase II enzymes and reduced
DNA damage and DNA/​protein cross links in Benzo(a)pyrene induced experimental
lung carcinogenesis.

Selvendiran K, Banu SM, Sakthisekaran D.

Department of Medical Biochemistry, Dr ALM Post Graduate Institute of Basic
Medical Sciences, University of Madras, Taramani Campus, Chennai, India.

In recent years, considerable emphasis has been focused on identifying new
chemopreventive agents, which could be useful for the human population. Piperine
is a pure, pungent alkaloid constituent of black and long peppers (piper nigrum
and piper longum), which is a most common spice used throughout the world. In
the present study, we examined the protective role of piperine during
experimental lung carcinogenesis with reference to its effect on DNA damage and
detoxification enzyme system. The activities of detoxifying enzymes such as
glutathione transferase (GST), quinone reductase (QR) and UDP/​glucuronosyl
transferase (UDP/​GT) were found to be decreased while the hydrogen peroxide
level was increased in the lung cancer bearing animals. Supplementation of
piperine (50 mg/kg bwt) enhanced the detoxification enzymes and reduced DNA
damage as determined by single cell electrophoresis. Furthermore, the
DNA/​Protein cross links which was found to be high in lung cancer bearing
animals was also modulated upon supplementation with piperine. Our present
results explain the understanding of unique association between
anti/​peroxidative effect of piperine and ultimately the capability of piperine
to prevent cancer.

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

PMID: 15724447 [PubMed /​ indexed for MEDLINE]

33: Nat Prod Res. 2005 Feb;19(2):143/​50.

Insecticidal amides from fruits of Piper nigrum Linn.

Siddiqui BS, Gulzar T, Begum S, Afshan F, Sattar FA.

HEJ Research Institute of Chemistry, International Centre for Chemical Sciences,
University of Karachi, Karachi /​ 75270, Pakistan. bina@khi.comsats.net.pk

The petroleum ether and ethyl acetate fractions of dried ground seeds of Piper
nigrum Linn. afforded sixteen compounds (1/​16) including one new insecticidal
amide, pipwaqarine (1) and six constituents (3,4,6,7,11,15) previously
unreported from this plant. The structure of (1) has been elucidated through
extensive 1D/​, 2D/​NMR spectral studies as,
1/​[13/​(3',4'/​methylenedioxyphenyl)/​2E,4E,12E/​tridecatrienoyl]/​N/​isopentylamide,
while those of known constituents through comparison of spectral data. 1
exhibited toxicity of 30ppm against fourth instar larvae of Aedes aegypti Liston
determined by WHO method. A portion of petroleum ether fraction was also
subjected to GC and GC/​MS analysis resulting in the identification of three
compounds (17/​19) using the NIST Mass spectral search program 1998 and Kovat's
retention indices. Two of these compounds, 17 and 18, are reported for the first
time from this plant.

PMID: 15715258 [PubMed /​ indexed for MEDLINE]

34: J Org Chem. 2005 Feb 18;70(4):1164/​76.

Nigramides A/​S, dimeric amide alkaloids from the roots of Piper nigrum.

Wei K, Li W, Koike K, Chen Y, Nikaido T.

Faculty of Pharmaceutical Sciences, Toho University, Miyama 2/​2/​1, Funabashi,
Chiba 274/​8510, Japan.

[structure: see text] Fifteen novel dimeric amide alkaloids possessing a
cyclohexene ring, nigramides A/​O (1/​15), as well as four novel dimeric amide
alkaloids possessing a cyclobutane ring, nigramides P/​S (17/​20), have been
isolated from the roots of Piper nigrum. Their structures were elucidated on the
basis of their spectroscopic data. The biosynthestic hypothesis of nigramides
A/​O (1/​15) was proposed by an intermolecular Diels/​Alder reaction from the
corresponding monomeric amides. On the basis of this biosynthetic hypothesis,
the first study of the thermal and Lewis acid mediated Diels/​Alder reactions of
piperine in different organic solvents and under solventless conditions is also
described.

PMID: 15704948 [PubMed /​ indexed for MEDLINE]

35: Phytomedicine. 2004 Nov;11(7/​8):697/​700.

Antibacterial constituents from the berries of Piper nigrum.

Reddy SV, Srinivas PV, Praveen B, Kishore KH, Raju BC, Murthy US, Rao JM.

Natural Product Laboratory, Indian Institute of Chemical Technology, Hyderabad
500 007, India.

Piper nigrum finds an extensive application in antibacterial preparations
belonging to Ayurvedic system of medicine. A bioguided extraction and
fractionation of the petroleum ether extract of the berries of P. nigrum
afforded 2E, 4E, 8Z/​N/​isobutyleicosatrienamide (1), pellitorine (2), trachyone
(3), pergumidiene (4) and isopiperolein B (5). Pergumidiene and trachyone are
isolated for the first time from P. nigrum. All the isolated compounds were
active against Bacillus subtilis, Bacillus sphaericus, and Staphylococcus aureus
amongst Gram + ve bacteria, and Klebsiella aerogenes and Chromobacterium
violaceum among Gram /​ve bacterial strains.

PMID: 15636188 [PubMed /​ indexed for MEDLINE]

36: Int J Tissue React. 2004;26(1/​2):43/​51.

Anti/​inflammatory activities of Aller/​7, a novel polyherbal formulation for
allergic rhinitis.

Pratibha N, Saxena VS, Amit A, D'Souza P, Bagchi M, Bagchi D.

Natural Remedies Research Center, Bangalore, India.

Allergic rhinitis is an immunological disorder and an inflammatory response of
nasal mucosal membranes. Allergic rhinitis, a state of hypersensitivity, occurs
when the body overreacts to a substance such as pollens or dust. A novel, safe
polyherbal formulation (Aller/​7/NR/​A2) has been developed for the treatment of
allergic rhinitis using a unique combination of extracts from seven medicinal
plants including Phyllanthus emblica, Terminalia chebula, Terminalia bellerica,
Albizia lebbeck, Piper nigrum, Zingiber officinale and Piper longum. Since
inflammation is an integral mechanistic component of allergy, the present study
aimed to determine the anti/​inflammatory activity of Aller/​7 in various in vivo
models. The efficacy of Aller/​7 was investigated in compound 48/80/​induced paw
edema both in Balb/c mice and Swiss Albino mice, carrageenan/​induced paw edema
in Wistar Albino rats and Freund's adjuvant/​induced arthritis in Wistar Albino
rats. The trypsin inhibitory activity of Aller/​7 was also determined and
compared with ovomucoid. At a dose of 250 mg/kg, Aller/​7 demonstrated 62.55%
inhibition against compound 48/80/​induced paw edema in Balb/c mice, while under
the same conditions prednisolone at an oral dose of 14 mg/kg exhibited 44.7%
inhibition. Aller/​7 significantly inhibited compound 48/80/​induced paw edema at
all three doses of 175, 225 or 275 mg/kg in Swiss Albino mice, while the most
potent effect was observed at 225 mg/kg. Aller/​7 (120 mg/kg, p.o.) demonstrated
31.3% inhibition against carrageenan/​induced acute inflammation in Wistar Albino
rats, while ibuprofen (50 mg/kg, p.o.) exerted 68.1% inhibition. Aller/​7 also
exhibited a dose/​dependent (150/​350 mg/kg) anti/​inflammatory effect against
Freund's adjuvant/​induced arthritis in Wistar Albino rats and an approximately
63% inhibitory effect was observed at a dose of 350 mg/kg. The trypsin
inhibitory activity of Aller/​7 was determined, using ovomucoid as a positive
control. Ovomucoid and Aller/​7 demonstrated IC50 concentrations at 1.5 and 9.0
microg/ml, respectively. These results demonstrate that this novel polyherbal
formulation is a potent anti/​inflammatory agent that can ameliorate the symptoms
of allergic rhinitis.

PMID: 15573692 [PubMed /​ indexed for MEDLINE]

37: Chem Pharm Bull (Tokyo). 2004 Nov;52(11):1349/​52.

New insecticidal amides from petroleum ether extract of dried Piper nigrum L.
whole fruits.

Siddiqui BS, Gulzar T, Mahmood A, Begum S, Khan B, Afshan F.

H.E.J. Research Institute of Chemistry, International Centre for Chemical
Sciences, University of Karachi, Karachi/​75270, Pakistan.
bina@khi.comsats.net.pk

The petroleum ether extract of dried ground whole fruits of Piper nigrum L.
afforded 20 compounds (1/​20) including two new insecticidal amides named as
pipnoohine (1), and pipyahyine (2), seven reported for the first time from this
plant (12, 13, 15/​17, 19, 20), and eleven known compounds (3/​11, 14, 18). The
structure of 1 has been elucidated as
(2E,4E,12Z)/​N/​(4/​methylpentyl)octadeca/​2,4,12/​trienamide and that of 2 as
(2E,4E,11E)/​12/​(benzo[1,3]dioxol/​5/​yl)/​N/​(3/​methylbutyl)dodeca/​2,4,11/​trien/​amid
e through extensive ID/​, 2D/​NMR spectral studies and chemical reactions. The
known compounds have been identified through comparison of their spectral data
with those reported in literature. 1 and 2 exhibited toxicity at 35.0 and 30.0
ppm respectively against fourth instar larvae of Aedes aegypti L. by WHO method.

PMID: 15516761 [PubMed /​ indexed for MEDLINE]

38: Biol Pharm Bull. 2004 Oct;27(10):1611/​6.

Melanogenesis stimulation in murine B16 melanoma cells by Piper nigrum leaf
extract and its lignan constituents.

Matsuda H, Kawaguchi Y, Yamazaki M, Hirata N, Naruto S, Asanuma Y, Kaihatsu T,
Kubo M.

School of Pharmaceutical Sciences, Kinki University, Higashiosaka, Osaka, Japan.
matsuda@phar.kindai.ac.jp

A methanolic extract from the leaves of Piper nigrum L. showed a significant
stimulatory effect on melanogenesis in cultured murine B16 melanoma cells.
Activity/​guided fractionation of the methanolic extract led to the isolation of
two known lignans, (/​)/​cubebin (1) and
(/​)/​3,4/​dimethoxy/​3,4/​desmethylenedioxycubebin (2), together with a new lignan,
(/​)/​3/​desmethoxycubebinin (3). Among these lignans, 1 and 2 showed a significant
stimulatory activity of melanogenesis without any significant effects on cell
proliferation.

PMID: 15467205 [PubMed /​ indexed for MEDLINE]

39: J Econ Entomol. 2004 Aug;97(4):1390/​403.

Efficacy of Piper (Piperaceae) extracts for control of common home and garden
insect pests.

Scott IM, Jensen H, Nicol R, Lesage L, Bradbury R, Sanchez/​Vindas P, Poveda L,
Arnason JT, Philogene BJ.

Biology Department, University of Ottawa, Ottawa, Ontario, K1N 6N5 Canada.

Extracts from three species of the plant family Piperaceae, Piper nigrum [L.],
Piper guineense [Schum & Thonn, and Piper tuberculatum [Jacq.], were tested for
efficacy against insects from five orders. All three species contain isobutyl
amides, plant secondary compounds that act as neurotoxins in insects. These
materials are considered safe to mammals because Piper spp. were used for
centuries for spice and medicinal purposes. When 24/​h P. nigrum LC50 values were
compared between common insect pests from eastern Canada and the northeastern
United States, the most sensitive species in order of increasing lethal
concentration were eastern tent caterpillar, Malacosoma americanum (F.) <
European pine sawfly larvae, Neodiprion sertifer (Geoffroy) < spindle ermine
moth larvae, Yponomeuta cagnagella [Hubner] < viburnum leaf beetle larvae,
Pyrrhalta viburni [Paykull] < stripped cucumber beetle adults, Acalymma vittatum
(F.) < Colorado potato beetle adults, Leptinotarsa decemlineata (Say) < Japanese
beetle adults, Popillia japonica [Newman] < hairy chinch bug, Blissus
leucopterus hirtis [Montandon]. The life stage tested was the point at which
each species causes the greatest amount of damage to the host plant and the
point at which most gardeners would likely choose to treat with a conventional
synthetic insecticide. Greenhouse trials revealed that the pepper formulations
also had a repellent activity, thus protecting plant leaves from 1) herbivory
(lily leaf beetle, Lilioceris lilii [Scopoli], adults and larvae and stripped
cucumber beetle adults) and 2) oviposition [European corn borer, Ostrinia
nubilalis (Hubner)]. Combinations with other botanical extracts were additive at
best in toxicity and repellent trials. Nontarget toxicity to beneficial
invertebrates is a possibility because the P. nigrum LC50 for beneficial
ladybird beetles was 0.2%. P. nigrum extracts can provide a reasonable level of
control against lepidopteran and European pine sawfly larvae and also will work
as a short/​term repellent and feeding deterrent. It is recommended that the use
of Piper extracts be restricted to small/​scale spot treatments in residential
areas where insect pest outbreaks have occurred.

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

PMID: 15384353 [PubMed /​ indexed for MEDLINE]

40: Drugs Exp Clin Res. 2004;30(3):99/​109.

Antioxidant properties of Aller/​7, a novel polyherbal formulation for allergic
rhinitis.

D'Souza P, Amit A, Saxena VS, Bagchi D, Bagchi M, Stohs SJ.

Natural Remedies Research Center, Bangalore, India.

Allergic rhinitis, a frequently occurring immunological disorder affecting men,
women and children worldwide, is a state of hypersensitivity that occurs when
the body overreacts to a substance such as pollen, mold, mites or dust. Allergic
rhinitis exerts inflammatory response and irritation of the nasal mucosal
membranes leading to sneezing; stuffy/runny nose; nasal congestion; and itchy,
watery and swollen eyes. A novel, safe polyherbal formulation (Aller/​7/NR/​A2)
has been developed for the treatment of allergic rhinitis using a unique
combination of extracts from seven medicinal plants including Phyllanthus
emblica, Terminalia chebula, Terminalia bellerica, Albizia lebbeck, Piper
nigrum, Zingiber officinale and Piper longum. In this study, the antioxidant
efficacy of Aller/​7 was investigated by various assays including hydroxyl
radical scavenging assay, superoxide anion scavenging assay,
1,1/​diphenyl/​2/​picryl hydrazyl (DPPH) and
2,2/​azinobis/​ethyl/​benzothiozoline/​sulphonic acid diammonium salt (ABTS) radical
scavenging assays. The protective effect of Aller/​7 on free radical/​induced
lysis of red blood cells and inhibition of nitric oxide release by Aller/​7 in
lipopolysaccharide/​stimulated murine macrophages were determined. Aller/​7
exhibited concentration/​dependent scavenging activities toward biochemically
generated hydroxyl radicals (IC50 741.73 microg/ml); superoxide anion (IC50
24.65 microg/ml by phenazine methosulfate/​nicotinamide adenine dinucleotide
[PMS/​NADH] assay and IC50 4.27 microg/ml by riboflavin/nitroblue tetrazolium
[NBT] light assay), nitric oxide (IC50 16.34 microg/ml); 1,1/​diphenyl/​2/​picryl
hydrazyl (DPPH) radical (IC50 5.62 microg/ml); and
2,2/​azinobis/​ethyl/​benzothiozoline/​sulphonic acid diammonium salt (ABTS) radical
(IC50 7.35 microg/ml). Aller/​7 inhibited free radical/​induced hemolysis in the
concentration range of 20/​80 microg/ml. Aller/​7 also significantly inhibited
nitric oxide release from lipopolysaccharide/​stimulated murine macrophages.
These results demonstrate that Aller/​7 is a potent scavenger of free radicals
and that it may serve.

Publication Types:
Comparative Study

PMID: 15366786 [PubMed /​ indexed for MEDLINE]

41: Indian J Exp Biol. 2003 Feb;41(2):135/​40.

Enzymatic and non/​enzymatic antioxidants in selected Piper species.

Karthikeyan J, Rani P.

Department of Biochemistry, PSG College of Arts and Science, Coimbatore 641 004,
India.

Piper species, commonly used in diet and traditional medicine were assessed for
their antioxidant potential. Catalase activity was predominated in Piper longum,
followed by Piper cubeba, green pepper, Piper brachystachyum and Piper nigrum.
P. nigrum was richest in glutathione peroxidase and glucose/​6/​phosphate
dehydrogenase, green pepper was richest in peroxidase and vitamin C while
vitamin E was more in P. longum and P. nigrum. P. brachystachyum and P. longum
were rich sources of vitamin A. All the Piper species had GSH content of around
1 to 2 nM/g tissue. The antioxidant components of Piper species constitute a
very efficient system in scavenging a wide variety of reactive oxygen species.
Antioxidant potential of Piper species was further confirmed by their ability to
curtail in vitro lipid peroxidation by around 30/​50% with concomitant increase
in GSH content.

PMID: 15255605 [PubMed /​ indexed for MEDLINE]

42: Nat Prod Res. 2004 Oct;18(5):473/​7.

Piptigrine, a new insecticidal amide from Piper nigrum Linn.

Siddiqui BS, Gulzar T, Begum S, Afshan F.

H.E.J. Research Institute of Chemistry, International Centre for Chemical
Sciences, University of Karachi, Karachi/​75270, Pakistan.
bina@khi.comsats.net.pk

A new insecticidal amide piptigrine (1) possessing highly extended conjugation
was isolated from the dried ground seeds of Piper nigrum Linn. along with the
known amides piperine and wisanine (hitherto unreported from this plant). The
structure of 1 has been elucidated as
1/​[9/​(3',4'/​methylenedioxyphenyl)/​4E,6E,8E/​nonatrienoyl]piperidine through
extensive 1D/​ and 2D/​NMR (COSY/​45, NOESY, J/​resolved, HMQC, HMBC and NOESY
studies. The known compounds have been identified through comparison of their
spectral data with those reported in literature. 1 exhibited toxicity of 15.0
ppm against fourth instar larvae of Aedes aegypti Liston.

PMID: 15248617 [PubMed /​ indexed for MEDLINE]

43: Redox Rep. 2004;9(2):105/​10.

Antioxidant efficacy of black pepper (Piper nigrum L.) and piperine in rats with
high fat diet induced oxidative stress.

Vijayakumar RS, Surya D, Nalini N.

Department of Biochemistry, Annamalai University, Annamalai Nagar, Tamilnadu,
India.

The present study was aimed to explore the effect of black pepper (Piper nigrum
L.) on tissue lipid peroxidation, enzymic and non/​enzymic antioxidants in rats
fed a high/​fat diet. Thirty male Wistar rats (95/​115 g) were divided into 5
groups. They were fed standard pellet diet, high/​fat diet (20% coconut oil, 2%
cholesterol and 0.125% bile salts), high/​fat diet plus black pepper (0.25 g or
0.5 g/kg body weight), high/​fat diet plus piperine (0.02 g/kg body weight) for a
period of 10 weeks. Significantly elevated levels of thiobarbituric acid
reactive substances (TBARS), conjugated dienes (CD) and significantly lowered
activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase
(GPx), glutathione/​S/​transferase (GST) and reduced glutathione (GSH) in the
liver, heart, kidney, intestine and aorta were observed in rats fed the high fat
diet as compared to the control rats. Simultaneous supplementation with black
pepper or piperine lowered TBARS and CD levels and maintained SOD, CAT, GPx,
GST, and GSH levels to near those of control rats. The data indicate that
supplementation with black pepper or the active principle of black pepper,
piperine, can reduce high/​fat diet induced oxidative stress to the cells.

PMID: 15231065 [PubMed /​ indexed for MEDLINE]

44: J Nat Prod. 2004 Jun;67(6):1005/​9.

New amide alkaloids from the roots of Piper nigrum.

Wei K, Li W, Koike K, Pei Y, Chen Y, Nikaido T.

Faculty of Pharmaceutical Science, Toho University, Miyama 2/​2/​1, Funabashi,
Chiba 274/​8510, Japan.

Seven new amide alkaloids, named N/​isobutyl/​4/​hexanoyl/​4/​hydroxypyrrolidin/​1/​one
(1), (+//​)/​erythro/​1/​(1/​oxo/​4,5/​dihydroxy/​2E/​decaenyl)piperidine (2),
(+//​)/​threo/​1/​(1/​ oxo/​4,5/​dihydroxy/​2E/​decaenyl)piperidine (3),
(+//​)/​threo/​N/​isobutyl/​4,5/​dihydroxy/​2E/​octaenamide (4),
1/​(1,6/​dioxo/​2E,4E/​decadienyl)piperidine (5),
1/​[1/​oxo/​3(3,4/​methylenedioxy/​5/​methoxyphenyl)/​2Z/​propenyl]piperidine (6), and
1/​[1/​oxo/​5(3,4/​methylenedioxyphenyl)/​2Z,4E/​pentadienyl]pyrrolidine (7), were
isolated from the roots of Piper nigrum, together with 32 known amides. Their
structures were elucidated on the basis of spectroscopic analysis and chemical
evidence.

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

PMID: 15217283 [PubMed /​ indexed for MEDLINE]

45: J Ethnopharmacol. 2004 Apr;91(2/​3):277/​80.

Pharmacokinetic and pharmacodynamic studies on interaction of "Trikatu" with
diclofenac sodium.

Lala LG, D'Mello PM, Naik SR.

Department of Pharmacognosy and Phytochemistry, Prin. K.M. Kundnani College of
Pharmacy, Dr. R.G. Thadani Marg, Worli, Mumbai/​400 018, India.
luxlala@rediffmail.com

"Trikatu"/​an Ayurvedic formulation comprising of a 1:1:1 ratio of dried fruits
of Piper nigrum, Piper longum and dried rhizomes of Zingiber officinale is
widely used to enhance the bioavailability of drugs, like vasicine,
indomethacin, etc. The enhanced biological response might lead to alteration of
therapeutic regimens of commonly prescribed drugs. The present work was aimed to
study the effect of concomitant administration of Trikatu on the
pharmacokinetics and pharmacodynamics of diclofenac sodium, a frequently
prescribed non/​steroidal anti/​inflammatory drug, having a poor oral
bioavailability (54 +//​ 2%). The effect of Trikatu on the bioavailability
profile of diclofenac sodium was studied in rabbits. It was observed that
Trikatu significantly decreased the serum levels of diclofenac sodium. The
pharmacodynamic study was carried out to evaluate the effect of Trikatu on the
anti/​inflammatory activity of diclofenac sodium using carragenin/​induced rat paw
edema model. It was observed that the mean percent edema inhibition shown by the
combination of Trikatu and diclofenac was similar to that shown by Trikatu alone
but significantly less than that shown by diclofenac alone. Thus, the
experimental findings indicated that Trikatu pretreatment might decrease the
bioavailability of certain drugs probably through a drug/​herb interaction
thereby adversely affecting the therapeutic efficacy of these drugs.

PMID: 15120451 [PubMed /​ indexed for MEDLINE]

46: J Agric Food Chem. 2004 May 5;52(9):2582/​6.

Effect of storage on the essential oil composition of Piper nigrum L. fruits of
different ripening states.

Orav A, Stulova I, Kailas T, Muurisepp M.

Institute of Chemistry, Faculty of Science, Tallinn Technical University,
Ehitajate tee 5, Tallinn 19086, Estonia. aorav@chemnet.ee

The qualitative and quantitative composition of the essential oil from black,
green, and white pepper was determined by using a simultaneous distillation and
extraction micromethod for oil isolation and gas chromatography (GC)/flame
ionization detection (FID) and GC/mass spectrometry (MS) analysis techniques.
The most abundant compounds in pepper oils were (E)/​beta/​caryophyllene
(1.4/​70.4%), limonene (2.9/​38.4%), beta/​pinene (0.7/​25.6%), Delta/​3/​carene
(1.7/​19.0%), sabinene (0/​12.2%), alpha/​pinene (0.3/​10.4%), eugenol (0.1/​41.0%),
terpinen/​4/​ol (0/​13.2%), hedycaryol (0/​9.1%), beta/​eudesmol (0/​9.7%), and
caryophyllene oxide (0.1/​7.2%). Green pepper corn obtained by a sublimation
drying method gave more oil (12.1 mg/g) and a much higher content of
monoterpenes (84.2%) in the oil than air/​dried green pepper corn (0.8 mg/g and
26.8%, respectively). The oil from ground black pepper contained more
monoterpenes and less sesquiterprnes and oxygenated terpenoids as compared to
green and white pepper oils. After 1 year of storage of pepper samples in a
glass vessel at room temperature, the amount of the oils isolated decreased, the
content of terpenes decreased, and the amount of oxygenated terpenoids
increased. Differently from other pepper samples, 1 year storage of green pepper
corn raised the oil amount more than twice of both drying methods.

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

PMID: 15113161 [PubMed /​ indexed for MEDLINE]

47: Afr J Med Med Sci. 2002 Dec;31(4):293/​5.

Effects of piperine on gastric acid secretion in albino rats.

Ononiwu IM, Ibeneme CE, Ebong OO.

Department of Pharmacology, College of Health Sciences, University of Port
Harcourt, Rivers State, Nigeria. ugoeze_inno@yahoo.com

Piperine, the pungent principle in Piper nigrum and Piper guinensis was studied
for its effect on gastric acid secretion in white albino rats. Increasing the
dose from 20 mg kg(/​1) weight to 142 mg kg(/​1) body weight produced dose
dependent increases in gastric acid secretion. When compared with control basal
acid secretion, these increases were significant (P<0.05). 20 mg kg(/​1) produced
a 22.2% (n=7) increase, while the highest dose employed in this study (142 mg
kg(/​1)) produced 334.6% (n=7) increase in the gastric acid secretion. Piperine
was however about 40 times less effective than histamine in increasing gastric
acid secretion. The effect of piperine was significantly antagonized by
cimetidine (1 mg kg(/​1), n=6) but not by atropine (1 mg kg(/​1), n=6). Any
involvement of cholinergic receptors in the observed piperine/​induced increase
in gastric acid secretion is thus excluded. There is however an indication that
stimulation of histamine H2 receptors by piperine is likely to be involved in
the increased acidity induced by piperine.

Publication Types:
Comparative Study

PMID: 15027765 [PubMed /​ indexed for MEDLINE]

48: Magn Reson Chem. 2004 Mar;42(3):355/​9.

Complete 1H and 13C NMR assignments of two phytosterols from roots of Piper
nigrum.

Wei K, Li W, Koike K, Pei Y, Chen Y, Nikaido T.

School of Chinese Traditional Medicine, Shenyang Pharmaceutical University,
Shenyang 110016, China.

Using modern NMR techniques, including DQF/​COSY, NOESY, HETCOR and HMBC, the
full assignments of all 1H and 13C chemical shifts were made for
stigmastane/​3,6/​dione and stigmast/​4/​ene/​3,6/​dione, isolated from the roots of
Piper nigrum (Piperaceae). Their stereochemistry was resolved by a combination
of 2D NOESY data and analysis of coupling constants. The two compounds were
isolated from the genus Piper for the first time. Copyright 2004 John Wiley &
Sons, Ltd.

PMID: 14971021 [PubMed /​ indexed for MEDLINE]

49: Drugs Exp Clin Res. 2003;29(3):107/​15.

Mast cell stabilization, lipoxygenase inhibition, hyaluronidase inhibition,
antihistaminic and antispasmodic activities of Aller/​7, a novel botanical
formulation for allergic rhinitis.

Amit A, Saxena VS, Pratibha N, D'Souza P, Bagchi M, Bagchi D, Stohs SJ.

Natural Remedies Research Center, Bangalore, India.

Allergic rhinitis, also known as hay fever, rose fever or summer catarrh, is a
major challenge to health professionals. A large number of the world's
population, including approximately 40 million Americans, suffers from allergic
rhinitis. A novel, botanical formulation (Aller/​7) has been developed for the
treatment of allergic rhinitis using a combination of extracts from seven
medicinal plants, including Phyllanthus emblica, Terminalia chebula, T.
bellerica, Albizia lebbeck, Piper nigrum, Zingiber officinale and P. longum,
which have a proven history of efficacy and health benefits. The clinical
manifestations of allergy are due to a number of mediators that are released
from mast cells. The effect of Aller/​7 on rat mesenteric mast cell degranulation
was studied by incubating different concentrations of Aller/​7 and challenging
them with a degranulating agent, compound 48/80. The inhibitory activity of
Aller/​7 was determined against lipoxygenase and hyaluronidase, the key enzymes
involved in the initiation and maintenance of inflammatory responses.
Furthermore, most of these manifestations are due to histamine, which causes
vasodilatation, increasing capillary permeability and leading to
bronchoconstriction. Hence, the antihistaminic activity of Aller/​7 was
determined is isolated guinea pig ileum substrate using cetirizine as a positive
control. The antispasmodic effect of Aller/​7 on contractions of guinea pig
tracheal chain was determined using papaverine and cetirizine as controls.
Aller/​7 exhibited potent activity in all these in vitro models tested, thus
demonstrating the novel anti/​allergic potential of Aller/​7.

Publication Types:
Comparative Study

PMID: 14708456 [PubMed /​ indexed for MEDLINE]

50: Arch Insect Biochem Physiol. 2003 Dec;54(4):212/​25.

Botanical insecticides for controlling agricultural pests: piperamides and the
Colorado Potato Beetle Leptinotarsa decemlineata say (Coleoptera:
Chrysomelidae).

Scott IM, Jensen H, Scott JG, Isman MB, Arnason JT, Philogene BJ.

Biology Department, University of Ottawa, Ottawa, Ontario, Canada.

The efficacy of extracts from two Piperaceae species, Piper nigrum L. and P.
tuberculatum Jacq. were evaluated using larvae and adults of the Colorado Potato
Beetle Leptinotarsa decemlineata (Say). Young larvae and neonates were the most
susceptible; a 24/​h LD(50) of 0.064% extract of P. tuberculatum was determined
for 4/​day/​old larvae, while 0.05% extract of P. nigrum reduced larval survival
up to 70% within one week after treatment of potato Solanum tuberosum L.
(Solanaceae) plants. When an insecticide resistant strain of L. decemlineata
larvae was tested with the P. tuberculatum extract, there was less than a 2/​fold
tolerance ratio compared to the 22/​fold tolerance ratio to cypermethrin, a
pyrethroid. Older larvae, pre/​pupal stage and adults, were less sensitive to the
P. nigrum extracts; the 24/​h LD(50) was 0.5% (95% C.I. = 0.36, 0.65). However,
the same concentration was equally effective under field conditions. In the
greenhouse, P. nigrum at 0.5% was as effective at reducing adult L. decemlineata
feeding as combinations with 2 separate botanical mixtures, garlic and lemon
grass oil. Under field conditions, the residual activity of the P. nigrum
extracts was less than 3 h. When adult L. decemlineata were placed on treated
plants exposed to full sunlight for 0, 1.5, and 3 h, leaf damage progressively
increased as the main active compound, piperine, was found to degrade by 80%
after 3 h. An in vitro polysubstrate monoxygenase (PSMO) enzyme assay, using the
substrate methoxyresorufin O/​demethylation (MROD), determined that the principal
P. nigrum active compound, piperine, is responsible for inhibition of that
specific enzyme. The results suggest that Piper extracts could be used
effectively as contact botanical insect control agents to protect potato plants
from developing L. decemlineata larvae at concentrations less than 0.1%. There
is also potential for Piper extracts to control insecticide resistant
populations in conjunction with other integrated pest management (IPM)
strategies used in conventional and organic agriculture. Copyright 2003
Wiley/​Liss, Inc.

Publication Types:
Comparative Study

PMID: 14635182 [PubMed /​ indexed for MEDLINE]

51: J Ethnopharmacol. 2003 Dec;89(2/​3):261/​4.

Screening for acetylcholinesterase inhibitory activity in plants used in Thai
traditional rejuvenating and neurotonic remedies.

Ingkaninan K, Temkitthawon P, Chuenchom K, Yuyaem T, Thongnoi W.

Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of
Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand.
kornkanoki@hotmail.com

Acetylcholinesterase (AChE) inhibitor has been used as a drug for the
symptomatic treatment of Alzheimer's disease. In order to search for new AChE
inhibitors, 32 plants used in Thai traditional rejuvenating and neurotonic
remedies were collected. The plant methanolic extracts were tested for AChE
inhibitory activity using Ellman's colorimetric method in 96/​welled microplates.
The results showed that the methanolic extracts from roots of Stephania suberosa
Forman. and Tabernaemontana divaricata (L.) R.Br. ex Roem. & Schult. at
concentration of 0.1 mg/ml inhibited more than 90% of AChE activity. At the same
concentration, four extracts, i.e. stems of Piper interruptum Opiz., seeds of
Piper nigrum L., rootbarks of Butea superba Roxb. and roots of Cassia fistula L.
extracts showed 50/​65% inhibitory activity on AChE. The rest of the extracts
showed the AChE inhibitory activity below 50%.

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

PMID: 14611889 [PubMed /​ indexed for MEDLINE]

52: J Trace Elem Med Biol. 2003;17(2):85/​90.

Element analysis and biological studies on ten oriental spices using XRF and
Ames test.

Al/​Bataina BA, Maslat AO, Al/​Kofahil MM.

Physics Department, Yarmouk University, Irbid, Jordan.

Ten oriental spices were analyzed for their element composition using X/​ray
fluorescence (XRF): nutmeg (Myristica fragrans), coriander (Coriandrum sativum),
safflower (Carthamus tinctorius), caraway (Carum carvi), Sicilian sumac (Rhus
coriaria), aniseed (Anisum vulgare), black pepper (Piper nigrum), cardamom
(Elettaria cardamomum), cumin (Cuminum cyminum) and nigella (Nigella sativum).
The spices were found to contain the following elements: Mg, Al, Si, P, S, Cl,
K, Ca, Ti, Mn, Fe, Cu and Zn, with varying concentrations. Mutagenic studies
using Salmonella typhimurium strains TA97a, TA98, TA100, and TA102 showed that
the above spices have no base pair substitution mutagenic activity. However, a
weak frameshift mutagenicity has been shown by nutmeg and a very weak oxidative
mutagenic action has been revealed by cumin.

PMID: 14531636 [PubMed /​ indexed for MEDLINE]

53: Horm Metab Res. 2003 Sep;35(9):523/​6.

Piperine lowers the serum concentrations of thyroid hormones, glucose and
hepatic 5'D activity in adult male mice.

Panda S, Kar A.

School of Life Sciences, Devi Ahilya University, Indore, India.

Piperine, the main alkaloid of Piper nigrum fruits, was evaluated for its
thyroid hormone and glucose regulatory efficacy in adult male Swiss albino mice.
Its daily oral administration (2.50 mg/kg) for 15 days lowered the serum levels
of both the thyroid hormones, thyroxin (T (4)) and triiodothyronine (T (3)) as
well as glucose concentrations with a concomitant decrease in hepatic 5'D enzyme
and glucose/​6/​phospatase (G/​6/​Pase) activity. However, no significant
alterations were observed in animals treated with 0.25 mg/kg of piperine in any
of the activities studied except an inhibition in serum T (3) concentration. The
decrease in T (4), T (3) concentrations and in G/​6/​Pase were comparable to that
of a standard antithyroid drug, Proylthiouracil (PTU). The hepatic
lipid/​peroxidation (LPO) and the activity of endogenous antioxidants, superoxide
dismutase (SOD), and catalase (CAT) were not significantly altered in either of
the doses. It appears that the action of P. nigrum on thyroid functions is
mediated through its active alkaloid, piperine. We also suggest that a higher
dose of piperine may inhibit thyroid function and serum glucose concentration in
euthyroid individuals.

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

PMID: 14517767 [PubMed /​ indexed for MEDLINE]

54: Microbiol Res. 2003;158(2):91/​7.

Screening of antagonistic bacteria for biological control of nursery wilt of
black pepper (Piper nigrum).

Anith KN, Radhakrishnan NV, Manomohandas TP.

Department of Plant Pathology, College of Agriculture, Kerala Agricultural
University, Vellayani, Trivandrum, Kerala 695 522, India. knanith@yahoo.com

Bacterial antagonists of Phytophthora capsici were isolated from underground
shoot portions of rooted cuttings of black pepper. Initially isolates were
screened by dual culture on potato dextrose agar and carrot agar. Further, a
screening was done on black pepper shoots for supression of lesion caused by the
pathogen. Most of the antagonists showed varying levels of antagonism in the
dual culture and the shoot assay. Isolate PN/​026, showing the highest
suppression of lesion development in the shoot assay was found to be the most
efficient antagonist in reducing Phytophthora capsici induced nursery wilt of
black pepper. This screening involving the host, pathogen, and the antagonist,
performed on black pepper shoot (the planting material for this vegetatively
propagated crop), could be used as a rapid and reliable method for the isolation
of efficient bacterial antagonists of P. capsici.

PMID: 12906381 [PubMed /​ indexed for MEDLINE]

55: J Agric Food Chem. 2003 Aug 13;51(17):4853/​60.

Extraction of chili, black pepper, and ginger with near/​critical CO2, propane,
and dimethyl ether: analysis of the extracts by quantitative nuclear magnetic
resonance.

Catchpole OJ, Grey JB, Perry NB, Burgess EJ, Redmond WA, Porter NG.

Industrial Research Limited, P.O. Box 31/​310, Lower Hutt, New Zealand.
o.catchpole@irl.cri.nz

Ginger, black pepper, and chili powder were extracted using near/​critical carbon
dioxide, propane, and dimethyl ether on a laboratory scale to determine the
overall yield and extraction efficiency for selected pungent components. The
temperature dependency of extraction yield and efficiency was also determined
for black pepper and chili using propane and dimethyl ether. The pungency of the
extracts was determined by using an NMR technique developed for this work. The
volatiles contents of ginger and black pepper extracts were also determined.
Extraction of all spice types was carried out with acetone to compare overall
yields. Subcritical dimethyl ether was as effective at extracting the pungent
principles from the spices as supercritical carbon dioxide, although a
substantial amount of water was also extracted. Subcritical propane was the
least effective solvent. All solvents quantitatively extracted the gingerols
from ginger. The yields of capsaicins obtained by supercritical CO(2) and
dimethyl ether were similar and approximately double that extracted by propane.
The yield of piperines obtained by propane extraction of black pepper was low at
approximately 10% of that achieved with dimethyl ether and CO(2), but improved
with increasing extraction temperature.

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

PMID: 12903935 [PubMed /​ indexed for MEDLINE]

56: Zhongguo Zhong Yao Za Zhi. 2002 May;27(5):328/​33.

[Comparison of the chemical constituents and pharmacological action of Piper
nigrum Linn. with P. methysticum forst.]

[Article in Chinese]

Wei K, Dou DQ, Pei YP, Chen YJ.

Department of Phytochemistry, Shenyang Pharmaceutical University, Shenyang
110016, Liaoning, China

Publication Types:
Comparative Study
Review

PMID: 12814095 [PubMed /​ indexed for MEDLINE]

57: Indian J Exp Biol. 2002 Mar;40(3):277/​81.

Effect of co/​administration of piperine on pharmacokinetics of beta/​lactam
antibiotics in rats.

Hiwale AR, Dhuley JN, Naik SR.

Research and Development Division of Hindustan Antibiotics Limited, Pimperi,
Pune 411 018, India.

Co/​administration of piperine, an alkaloid isolated from Piper nigrum L.
enhanced bioavailability of beta lactam antibiotics, amoxycillin trihydrate and
cefotaxime sodium significantly in rats. The improved bioavailability is
reflected in various pharmacokinetic parameters viz. tmax, Cmax, t(1/2) and AUC,
of these antibiotics. The increased bioavailability could be attributed to the
effect of piperine on microsomal metabolising enzymes or enzymes system.

PMID: 12635696 [PubMed /​ indexed for MEDLINE]

58: Mol Biotechnol. 2003 Jan;23(1):1/​10.

Cloning, DNA sequence, and expression of Aeromonas caviae WS7b chitinase gene.

Malik A, Wenuganen S, Suwanto A, Tjahjono B.

South East Asian Regional Center for Tropical Biology (SEAMEO BIOTROP), Jl. Raya
Tajur Km 6, Bogor, Indonesia.

A chitinase/​producing bacterium, designated WS7b, was isolated from a soil
sample obtained from a black/​pepper plantation on Bangka Island, Indonesia.
Fatty/​acid methyl/​ester analysis indicated that the isolate was Aeromonas
caviae. A chitinase gene from WS7b was cloned in a pUC19/​based plasmid vector,
but without its natural promoter. The complete nucleotide sequence of the gene
was determined, and the structural gene consisted of a 2748/​bp region encoding
864 amino acids. DNA sequence analysis indicated that the gene had been cloned
without its promoter, and this was confirmed by chitinase/​plate assay of the
truncated version of the gene in Escherichia coli. The chitinase gene product
showed amino/​acid sequence similarity to chiA from A. caviae. Chitinase enzyme
activity was determined spectrophotometrically, using colloidal chitin azure as
substrate for extracellular and intracellular fractions. The ability of the
chitinase cloned in E. coli to hydrolyze chitin was less than that of the enzyme
in its indigenous host.

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

PMID: 12611264 [PubMed /​ indexed for MEDLINE]

59: Clin Exp Metastasis. 2002;19(8):703/​8.

Effect of piperine on the inhibition of lung metastasis induced B16F/​10 melanoma
cells in mice.

Pradeep CR, Kuttan G.

Amala Cancer Research Centre, Thrissur, Kerala, India.

The effect of piperine on the inhibition of lung metastasis induced by B16F/​10
melanoma cells was studied in C57BL/6 mice. Simultaneous administration of the
compound with tumor induction produced a significant reduction (95.2%) in tumor
nodule formation. Increased lung collagen hydroxyproline (22.37 microg/mg
protein) in the metastasized lungs of the control animals compared to normal
animals (0.95 microg/mg protein) was significantly reduced (2.59 microg/mg
protein) in the piperine/​treated animals. The high amount of uronic acid (355.83
microg/100 mg tissue) in the metastasized control animals was significantly
reduced (65 microg/100 mg tissue) in the animals treated with piperine. Lung
hexosamine content was also significantly reduced in the piperine/​treated
animals (0.98 mg/100 mg lyophilized tissue) compared to the untreated
tumor/​bearing animals (4.2 mg/100 mg lyophilized tissue). The elevated levels of
serum sialic acid and serum gamma glutamyl transpeptidase activity in the
untreated control animals was significantly reduced in the animals treated with
piperine. The piperine/​treated animals even survived the experiment (90 days).
Histopathology of the lung tissue also correlated with the lifespan of the
drug/​treated animals. Our results demonstrate the antimetastatic activity of
piperine, an alkaloid present in plants such as Piper nigrum and Piper longum.

PMID: 12553376 [PubMed /​ indexed for MEDLINE]

60: Jpn J Pharmacol. 2002 Nov;90(3):247/​53.

Effects of fragrance inhalation on sympathetic activity in normal adults.

Haze S, Sakai K, Gozu Y.

Product Development Center, Shiseido Co., Ltd., Hayabuchi, Yokohama, Japan.
shinchiro.haze@to.shiseido.co.jp

We investigated the effects of fragrance inhalation on sympathetic activity in
normal adult subjects using both power spectral analysis of blood pressure
fluctuations and measurement of plasma catecholamine levels. Fragrance
inhalation of essential oils, such as pepper oil, estragon oil, fennel oil or
grapefruit oil, resulted in 1.5/​ to 2.5/​fold increase in relative sympathetic
activity, representing low frequency amplitude of systolic blood pressure
(SBP/​LF amplitude), compared with inhalation of an odorless solvent, triethyl
citrate (P<0.05, each). In contrast, fragrance inhalation of rose oil or
patchouli oil caused a 40% decrease in relative sympathetic activity (P<0.01,
each). Fragrance inhalation of pepper oil induced a 1.7/​fold increase in plasma
adrenaline concentration compared with the resting state (P = 0.06), while
fragrance inhalation of rose oil caused a 30% decrease in adrenaline
concentration (P<0.01). Our results indicate that fragrance inhalation of
essential oils may modulate sympathetic activity in normal adults.

PMID: 12499579 [PubMed /​ indexed for MEDLINE]

61: J Chromatogr A. 2002 Nov 8;976(1/​2):265/​75.

Aroma compound analysis of Piper nigrum and Piper guineense essential oils from
Cameroon using solid/​phase microextraction/​gas chromatography, solid/​phase
microextraction/​gas chromatography/​mass spectrometry and olfactometry.

Jirovetz L, Buchbauer G, Ngassoum MB, Geissler M.

Institute of Pharmaceutical Chemistry, University of Vienna, Althanstrasse 14,
A/​1090 Vienna, Austria.

The investigation of aroma compounds of the essential oils of dried fruits of
black pepper (Piper nigrum) and black and white "Ashanti pepper" (Piper
guineense) from Cameroon by means of solid/​phase microextraction (SPME) was
carried out for the first time to identify the odorous target components
responsible for the characteristic odor of these valuable spices and food
flavoring products. By means of GC/​flame ionization detection (FID) and GC/​MS
(using different polar columns) the main compounds (concentration >3.0%,
calculated as area of GC/​FID analysis using a non/​polar fused/​silica open
tubular RSL/​200 column) of the SPME headspace samples of P. nigrum (black) and
P. guineense (black and white) were found to be: P. nigrum (black)/​/​germacrene D
(11.01%), limonene (10.26%), beta/​pinene (10.02%), alpha/​phellandrene (8.56%),
beta/​caryophyllene (7.29%), alpha/​pinene (6.40%) and cis/​beta/​ocimene (3.19%);
P. guineense (black)/​/​beta/​caryophyllene (57.59%), beta/​elemene (5.10%),
bicyclogermacrene (5.05%) and alpha/​humulene (4.86%); and P. guineense
(white)/​/​beta/​caryophyllene (51.75%), cis/​beta/​ocimene (6.61%), limonene
(5.88%), beta/​pinene (4.56%), linalool (3.97%) and alpha/​humulene (3.29%). The
most intense odor impressions of the essential oils of the various dried pepper
fruits were given byprofessional perfumers as follows: P nigrum (black)/​/​fine,
pleasant black pepper note; P. guineense (black)/​/​black pepper top/​note; and P.
guineense (white)/​/​pleasant white pepper note. These analytical results for the
SPME headspace samples of three different pepper species from Cameroon are in
accordance with the olfactoric data of the corresponding essential oils. A
GC/​sniffing technique was used to correlate the single odor impression of the
identified SPME headspace volatiles of the three investigated pepper samples
with the following results: themain compounds such as beta/​caryophyllene,
germacrene D, limonene, beta/​pinene, alpha/​phellandrene and alpha/​humulene, as
well as minor constituents such as delta/​carene, beta/​phellandrene, isoborneol,
alpha/​guaiene, sarisan, elemicin, calamenene, caryophyllene alcohol,
isoelemicin, T/​muurolol, cubenol and bulnesol, are of greatest importance for
the characteristic pepper odor notes of these three Piper samples. Further aroma
impressions can be attributed to mono/​ and sesquiterpenes, hexane, octane and
nonane derivatives.

PMID: 12462618 [PubMed /​ indexed for MEDLINE]

62: Food Chem Toxicol. 2003 Jan;41(1):41/​7.

Antimutagenic properties of bell and black peppers.

El Hamss R, Idaomar M, Alonso/​Moraga A, Munoz Serrano A.

Universite Abdelmalek Essaadi, Unite de Biologie Cellulaire et Moleculaire (BCM)
BP 2121, 93002 Tetouan, Morocco.

The wing Somatic Mutation And Recombination Test (SMART) in Drosophila
melanogaster was used to study the modulating action of bell pepper (Capsicum
annuum) and black pepper (Piper nigrum) in combination with the alkylating agent
methyl methanesulfonate (MMS) and the promutagen agent ethyl carbamate (EC).
Larvae trans/​heterozygous for the third chromosome recessive markers multiple
wing hairs (mwh) and flare/​3 [flr(3)] were fed genotoxins alone or in
combination with each of the two spices. Genetic changes induced in somatic
cells of the wing's imaginal discs lead to the formation of mutant clones on the
wing blade. Our results showed that bell pepper was effective in reducing the
mutational events induced by EC and MMS and black pepper was only effective
against EC. Pretreatment of 2/​day/​old larvae with the spices for 24 h followed
by a treatment with EC and MMS was only effective in reducing mutations induced
by EC. Suppression of metabolic activation or interaction with the active groups
of mutagens could be mechanisms by which the spices exert their antimutagenic
action.

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

PMID: 12453727 [PubMed /​ indexed for MEDLINE]

63: Meded Rijksuniv Gent Fak Landbouwkd Toegep Biol Wet. 2001;66(2a):473/​8.

Protection of stored maize against Sitophilus zeamais (Motsch.) by use of
essential oils of spices from Cameroon.

Ngamo LS, Ngassoum MB, Jirovetz L, Ousman A, Nukenine EC, Mukala OE.

Faculty of Sciences, Department of Biological Sciences, University of
Ngaoundere, P.O. Box 454, Ngaoundere, Cameroon.

In storage, maize as other cereals is currently attacked by insects. The main
specie present in Cameroon is Sitophilus zeamais (Coleop. Curculionidae). The
popular way to prevent its damages is the use of synthetic insecticides. These
chemicals extend their activities to non target animals. They are potentially
dangerous for consumers and are implicated in the pollution of the environment.
The development of products killing pests which are consumer/​friendly is to be
improved. In this respect, the use of essential oils from spices and aromatic
plants could help. Six essential oils were tested, 3 are causes of high insect
mortality. Xylopia aethiopica Dunal (Anonaceae) killed 97% of adults weevils and
Ocimum gratissimum, (L.) (Lamiaceae) 74% after 4 days after ingestion. Piper
nigrum (L.) (Piperaceae) killing more than 96% of weevil 48 hours after the
contact. The potential of these non toxic products to protect stored maize
against attacks of S. zeamais is hereby appraised.

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

PMID: 12425068 [PubMed /​ indexed for MEDLINE]

64: Biol Pharm Bull. 2002 Sep;25(9):1203/​8.

Biochemical properties of polysaccharides from black pepper.

Chun H, Shin DH, Hong BS, Cho WD, Cho HY, Yang HC.

Graduate School of Biotechnology, Korea University, Sungbuk/​Ku, Seoul.

The purified polysaccharides from Piper nigrum were prepared as follows: a hot
water extract of pepper seeds was fractionated by ultrafiltration with a
5/​kDa/​membrane cartridge. A fraction with 5 kDa or bigger molecules was
successively purified by open column chromatography on DEAE/​Toyopearl 650C and
Bio/​gel P/​60 with each active fraction, resulting in PN/​Ib and PN/​IIa, purified
anti/​complementary polysaccharides. None of the anti/​complementary activity of
any polysaccharide was changed by pronase digestion or polymyxin B treatment,
but they were decreased by periodate oxidation. Analysis of component sugar and
molecular mass determination of the anti/​complementary polysaccharides indicated
that PN/​Ib with an average molecular mass of 21 kDa contained 88.5% glucose and
other negligible minor monosaccharides, while PN/​IIa showed a different
monosaccharide composition, which contained a significant proportion of
galactose, arabinose, galacturonic acid and rhamnose. The molar ratio of
galactose and arabinose of PN/​IIa (48 kDa) was 1.93:1. PN/​1 did not react with
beta/​glucosyl Yariv reagent, however, PN/​IIa did react, which indicated that
PN/​IIa might be an arabinogalactan. Based upon these results, the usefulness of
purified anti/​complementary polysaccharides from Piper nigrum is suggested as a
supplement for immune enhancement.

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

PMID: 12230118 [PubMed /​ indexed for MEDLINE]

65: J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Sep 5;776(2):245/​9.

Liquid chromatographic method for determination of piperine in rat plasma:
application to pharmacokinetics.

Bajad S, Singla AK, Bedi KL.

Pharmacology Division, Regional Research Laboratory, Canal Road, Jammu 180 001,
India. sbajad@yahoo.com

Piperine, a major alkaloid of Piper longum and Piper nigrum has been reported to
have several pharmacological/toxicological effects. Though a number of methods
for analysis of this omnipresent food component in pepper fruits are available,
its analysis in body fluids has been largely neglected. A high/​performance
liquid chromatography method for the analysis of piperine in rat plasma is
presented in this communication. Analysis was performed using a Symmetry C(18)
column (250x4.6 mm) by isocratic elution with 25 mM KH(2)PO(4) (pH
4.5)/​acetonitrile (35:65) and UV detection at 340 nm. The calibration plot was
linear over the range studied (2/​2000 ng) with correlation coefficient of
0.9984. Limit of detection and limit of quantitation were 1 ng/ml and 3 ng/ml,
respectively. Good overall recovery (85.5+//​6%) was obtained with 4 ml ethyl
acetate and extraction time of 3 min. Intra/​ and inter/​assay coefficient of
variation was found to be less than 7.5%. Plasma concentration/​time profile of
piperine in a conscious rat implanted with jugular vein cannula was obtained
using this method. The method is simple, sensitive and reproducible. Copyright
2002 Elsevier Science B.V.

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

PMID: 12138007 [PubMed /​ indexed for MEDLINE]

66: Bioorg Med Chem. 2002 Sep;10(9):2981/​5.

CYP3A4 inhibitory activity of new bisalkaloids, dipiperamides D and E, and
cognates from white pepper.

Tsukamoto S, Tomise K, Miyakawa K, Cha BC, Abe T, Hamada T, Hirota H, Ohta T.

Faculty of Pharmaceutical Sciences, Kanazawa University, 13/​1 Takara/​machi,
Kanazawa 920/​0934, Japan.

Two new bisalkaloids, dipiperamides D and E, were isolated as inhibitors of a
drug metabolizing enzyme cytochrome P450 (CYP) 3A4 from the white pepper, Piper
nigrum. Their structures were elucidated by spectroscopic methods. Dipiperamides
D and E showed potent CYP3A4 inhibition with IC(50) values of 0.79 and 0.12
microM, respectively, and other metabolites from the pepper were moderately
active or inactive.

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

PMID: 12110320 [PubMed /​ indexed for MEDLINE]

67: Phytomedicine. 2002 Apr;9(3):224/​31.

Piperine modulates permeability characteristics of intestine by inducing
alterations in membrane dynamics: influence on brush border membrane fluidity,
ultrastructure and enzyme kinetics.

Khajuria A, Thusu N, Zutshi U.

Manitoba Institute of Cell Biology, Winnipeg, Canada. akhajuria@hsc.mb.ca

Piperine (1/​Piperoyl piperidine) is a major alkaloid of Piper nigrum Linn. and
Piper longum Linn. It is shown to possess bioavailability/​enhancing activity
with various structurally and therapeutically diverse drugs. The mechanism of
enhancing the bioavailability, is, however, not understood. We hypothesize that
piperine's bioavailability/​enhancing property may be attributed to increased
absorption, which may be due to alteration in membrane lipid dynamics and change
in the conformation of enzymes in the intestine. Results of membrane fluidity
studies using an apolar fluorescent probe, pyrene (which measures the fluid
properties of hydrocarbon core), showed an increase in intestinal brush border
membrane (BBM) fluidity. Piperine also stimulated Leucine amino peptidase and
Glycyl/​glycine dipeptidase activity, due to the alteration in enzyme kinetics.
This suggests that piperine could modulate the membrane dynamics due to its
apolar nature by interacting with surrounding lipids and hydrophobic portions in
the protein vicinity, which may decrease the tendency of membrane lipids to act
as stearic constrains to enzyme proteins and thus modify enzyme conformation.
Ultra structural studies with piperine showed an increase in microvilli length
with a prominent increase in free ribosomes and ribosomes on the endoplasmic
reticulum in enterocytes, suggesting that synthesis or turnover of cytoskeletal
components or membrane proteins may be involved in the observed effect. In
conclusion, it is suggested that piperine may be inducing alterations in
membrane dynamics and permeation characteristics, along with induction in the
synthesis of proteins associated with cytoskeletal function, resulting in an
increase in the small intestine absorptive surface, thus assisting efficient
permeation through the epithelial barrier.

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

PMID: 12046863 [PubMed /​ indexed for MEDLINE]

68: Compend Contin Educ Dent. 2001 May;22(5):425/​8, 430, 432 passim; quiz 440.

Effects of a nutritional supplement on periodontal status.

Munoz CA, Kiger RD, Stephens JA, Kim J, Wilson AC.

Center for Dental Research, Loma Linda University, School of Dentistry, Loma
Linda, California, USA.

Among the recommendations for the maintenance of gingival and periodontal
health, few have focused on the value of nutritional supplements. The purpose of
this study was to compare the effect of certain nutritional and plant/​derived
nutraceuticals and a placebo tablet in the reduction of gingivitis, bleeding,
probing depths, and attachment levels in a 60/​day two/​cell, randomized, parallel
clinical trial for patients with Type II periodontal disease. The vitamin
therapy was introduced as an adjunct to patient homecare to determine if there
was a quantifiable improvement to soft/​tissue health and periodontal damage.
Sixty/​three patients were randomly divided into two groups of 32 and 31 subjects
and given either a vitamin tablet containing seven active ingredients
(experimental treatment) or a placebo tablet. The clinical parameters assessed
were the gingival index (GI), bleeding index (BI), periodontal pocket depth
(PD), and attachment levels (AL), and were recorded at baseline and 60 days.
Patients took the assigned tablet at breakfast and at dinner after brushing
their teeth twice daily. After 60 days, the data showed a clinical reduction in
the GI, BI, and PD for the experimental group (P < .0001). There were no
significant changes for AL with either the experimental or the placebo group.
When the data were further analyzed for pocket depths of > or = 4 mm in patients
receiving the experimental treatment, there were clinically significant
improvements in the GI and PD from baseline to 60 days (P < .0001), but no
significant differences in the BI and AL. There were no statistical differences
in any of the indices when the data were compared between men and women. The
results of the present study suggest that a multi/​vitamin nutritional supplement
might be a beneficial adjunct to the required established periodontal treatment.

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

PMID: 11913269 [PubMed /​ indexed for MEDLINE]

69: J Agric Food Chem. 2002 Mar 27;50(7):1866/​70.

Larvicidal activity of isobutylamides identified in Piper nigrum fruits against
three mosquito species.

Park IK, Lee SG, Shin SC, Park JD, Ahn YJ.

School of Agricultural Biotechnology, Seoul National University, Suwon 441/​744,
Republic of Korea.

The insecticidal activity of materials derived from the fruits of Piper nigrum
against third instar larvae of Culex pipiens pallens, Aedes aegypti, and A.
togoi was examined and compared with that of commercially available piperine, a
known insecticidal compound from Piper species. The biologically active
constituents of P. nigrum fruits were characterized as the isobutylamide
alkaloids pellitorine, guineensine, pipercide, and retrofractamide A by
spectroscopic analysis. Retrofractamide A was isolated from P. nigrum fruits as
a new insecticidal principle. On the basis of 48/​h LC(50) values, the compound
most toxic to C. pipiens pallens larvae was pipercide (0.004 ppm) followed by
retrofractamide A (0.028 ppm), guineensine (0.17 ppm), and pellitorine (0.86
ppm). Piperine (3.21 ppm) was least toxic. Against A. aegypti larvae, larvicidal
activity was more pronounced in retrofractamide A (0.039 ppm) than in pipercide
(0.1 ppm), guineensine (0.89 ppm), and pellitorine (0.92 ppm). Piperine (5.1
ppm) was relatively ineffective. Against A. togoi larvae, retrofractamide A
(0.01 ppm) was much more effective, compared with pipercide (0.26 ppm),
pellitorine (0.71 ppm), and guineensine (0.75 ppm). Again, very low activity was
observed with piperine (4.6 ppm). Structure/​activity relationships indicate that
the N/​isobutylamine moiety might play a crucial role in the larvicidal activity,
but the methylenedioxyphenyl moiety does not appear essential for toxicity.
Naturally occurring Piper fruit/​derived compounds merit further study as
potential mosquito larval control agents or as lead compounds.

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

PMID: 11902925 [PubMed /​ indexed for MEDLINE]

70: Zhongguo Zhong Yao Za Zhi. 1998 Jan;23(1):42/​3, 63.

[Essential oil analysis and trace element study of the roots of Piper nigrum L.]

[Article in Chinese]

Ao P, Hu S, Zhao A.

Institute of Chinese Material Medica, China Academy of Traditional Chinese
Medicine, Beijing 100700.

Pepper roots contain 0.39% of essential oil. By GC/​MS method, 44 peaks and 22
compounds were obtained and identified. The major component was
trans/​caryophyllene. The trace metal content analysis showed that the heavy
metals were under the safety level.

Publication Types:
English Abstract

PMID: 11243157 [PubMed /​ indexed for MEDLINE]

71: Biosci Biotechnol Biochem. 2000 Sep;64(9):1967/​9.

Tyrosinase inhibitory activity of Bangladeshi indigenous medicinal plants.

Khanom F, Kayahara H, Tadasa K.

The United Graduate School of Agricultural Science, Gifu University, Japan.

The tyrosinase/​inhibitory activity of 15 kinds of Bangladeshi medicinal plants
was evaluated. Methanol extracts were prepared for screening tests, and other
kinds of extracts were also studied for those with high activity. Swertia
chirata, Piper nigrum, Glycyrrhiza glabra, Piper longam and Ocimum americanum
were screened as highly inhibiting samples. Methanol was found to be the most
efficient solvent for extracting the active compounds. The 50%
tyrosinase/​inhibitory concentration of the Glycyrrhiza glabra methanol extract
was 21.2 microg/ml.

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

PMID: 11055404 [PubMed /​ indexed for MEDLINE]

72: J Agric Food Chem. 2000 Oct;48(10):4656/​60.

Novel procedure for identification of compounds inhibitory to transcription of
genes involved in mycotoxin biosynthesis.

Annis SL, Velasquez L, Xu H, Hammerschmidt R, Linz J, Trail F.

Department of Botany and Plant Pathology and Department of Food Science and
Human Nutrition, Michigan State University, East Lansing, Michigan 48824, USA.

A novel assay is described for the identification and isolation of compounds
that inhibit the transcription of genes involved in mycotoxin biosynthesis. The
thin/​layer chromatography/​based assay was used to screen plant extracts for
compounds that would inhibit the expression of the beta/​glucuronidase reporter
gene under the control of an aflatoxin biosynthesis gene promoter in Aspergillus
parasiticus. The assay was used to track purification of an inhibitory compound,
cp2, from extracts of black pepper (Piper nigrum). Cp2 did not inhibit mycelial
growth or the expression of the beta/​tubulin gene but did inhibit aflatoxin
biosynthesis at the transcriptional level. Applications of cp2 to the control of
mycotoxins are discussed.

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

PMID: 11052714 [PubMed /​ indexed for MEDLINE]

73: Indian J Gastroenterol. 2000 Apr/​Jun;19(2):53/​6.

Influence of intragastric perfusion of aqueous spice extracts on acid secretion
in anesthetized albino rats.

Vasudevan K, Vembar S, Veeraraghavan K, Haranath PS.

Department of Pharmacology, Rajah Muthiah Medical College, Annamalainagar.

BACKGROUND: The effect of spices on gastric acid secretion is variable. Their
mechanism of action is also not well established. AIM: To study the effect of
spices on gastric acid secretion in anesthetized rats. METHODS: Aqueous extracts
(10% w/v) of red pepper (Capsicum annuum), fennel (Foeniculum vulgare),
omum/ajwan (Carum copticum), cardamom (Elettaria cardamomum), black pepper
(Piper nigrum), cumin (Cuminum cyminum) and coriander (Coriandrum sativum) were
prepared. The stomach of pentobarbitone/​anesthetized rats was perfused at 0.15
mL/min with aqueous extracts of spice or acetylcholine (1 microgram/mL or 10
micrograms/mL solutions, in 40 min blocks, twice in each experiment bracketed by
saline perfusions. The acid content in the samples was estimated by titration
with 0.1N NaOH with phenolphthalein as indicator. Atropine 1 microgram/mL was
added to the perfusion fluid in 28 experiments. In 32, acute gastric mucosal
injury was induced by leaving aspirin 125 mg/Kg in the stomach for 2 h before
perfusion. RESULTS: All the spices tested increased acid secretion in the
following declining order: red pepper, fennel, omum, cardamom, black pepper,
cumin, coriander. Red pepper increased acid secretion (mean [SEM] 0.93 [0.16] mL
0.1N HCl) to about 7 times the basal secretion (0.14 [0.05]; p < 0.005). The
increase in acid secretion by the other spices was as follows: fennel 0.42
(0.11) mL 0.1 N HCl from basal secretion (0.12 [0.03]) (p < 0.02); omum 0.33
(0.05) from 0.09 (0.02) (p < 0.01); cardamom 0.28 (0.04) from 0.10 (0.03) (p <
0.005); black pepper 0.19 (0.03) from 0.04 (0.01) (p < 0.005); cumin 0.12 (0.02)
from 0.08 (0.01) (p < 0.05); coriander 0.18 (0.03) from 0.09 (0.02) (p < 0.005).
Atropine abolished the acid secretion induced by acetylcholine and significantly
reduced acid induction by red pepper, omum and coriander, but not that by
fennel. In experiments with aspirin/​induced mucosal injury the basal acid
secretion was low; acid secretion by red pepper and fennel was reduced
significantly, but not that by acetylcholine. Cumin and coriander increased acid
secretion in injured stomachs. CONCLUSION: The spices tested increased gastric
acid secretion, in some by a cholinergic mechanism but by other mechanism(s) as
well. Red pepper produced maximum increase in acid secretion, but this was
significantly reduced in injured stomachs. Cumin and coriander increased gastric
secretion in injured stomachs.

PMID: 10812814 [PubMed /​ indexed for MEDLINE]

74: J Appl Microbiol. 2000 Feb;88(2):308/​16.

Antimicrobial agents from plants: antibacterial activity of plant volatile oils.

Dorman HJ, Deans SG.

Aromatic and Medicinal Plant Group, Scottish Agricultural College, Auchincruive,
South Ayrshire, UK.

The volatile oils of black pepper [Piper nigrum L. (Piperaceae)], clove
[Syzygium aromaticum (L.) Merr. & Perry (Myrtaceae)], geranium [Pelargonium
graveolens L'Herit (Geraniaceae)], nutmeg [Myristica fragrans Houtt.
(Myristicaceae), oregano [Origanum vulgare ssp. hirtum (Link) Letsw.
(Lamiaceae)] and thyme [Thymus vulgaris L. (Lamiaceae)] were assessed for
antibacterial activity against 25 different genera of bacteria. These included
animal and plant pathogens, food poisoning and spoilage bacteria. The volatile
oils exhibited considerable inhibitory effects against all the organisms under
test while their major components demonstrated various degrees of growth
inhibition.

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

PMID: 10736000 [PubMed /​ indexed for MEDLINE]

75: J Agric Food Chem. 1999 Dec;47(12):5072/​7.

Comparison of digestion methods for determination of trace and minor metals in
plant samples.

Lavilla I, Filgueiras AV, Bendicho C.

Departamento de Quimica Analitica y Alimentaria, Facultad de Ciencias (Quimica),
Universidad de Vigo, As Lagoas/​Marcosende s/n, 36200 Vigo, Spain.

In this paper, three dissolution methods using pressure digestion vessels (low/​,
medium/​, and high/​pressure vessels) for the determination of metals in plant
samples are described. The Plackett/​Burman saturated factorial design was used
to identify the significant factors influencing wet ashing and to select
optimized dissolution conditions. The three methods were statistically compared
(on/​way ANOVA) on the same sample; no significant differences were obtained. In
all cases the relative standard deviation values were <3%. The digestion method
based on the use of low/​pressure vessels and a microwave oven was validated
against CRM GBW07605 tea leaves. This method was applied to the determination of
Cu, Zn, Mn, Fe, Mg, and Ca in 22 different medicinal, aromatic, and seasoning
plants by flame/​atomic absorption spectrometry. The concentration intervals of
metal in the plants analyzed were the following: Cu, 4 (Allium sativum)/​35 (Thea
sinensis) microg g(/​1); Zn, 7 (Piper nigrum)/​90 (Betula alba) microg g(/​1); Mn,
9 (Allium sativum)/​939 (Caryophylus aromaticus) microg g(/​1); Fe, 33 (Allium
sativum)/​2486 (Anethum graveolens) microg g(/​1); Mg, 495 (Allium sativum)/​7458
(Ocimum basilicum) microg g(/​1); Ca, 386 (Allium sativum)/​21500 (Ocimum
basilicum) microg g(/​1).

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

PMID: 10606575 [PubMed /​ indexed for MEDLINE]

76: Planta Med. 1999 Oct;65(7):600/​3.

Stimulation of mouse melanocyte proliferation by Piper nigrum fruit extract and
its main alkaloid, piperine.

Lin Z, Hoult JR, Bennett DC, Raman A.

Department of Pharmacy, King's College London, U.K.

During a herbal screening programme to find potential repigmenting agents for
the treatment of vitiligo, Piper nigrum L. fruit (black pepper) extract was
found to possess growth/​stimulatory activity towards cultured melanocytes. Its
aqueous extract at 0.1 mg/ml was observed to cause nearly 300% stimulation of
the growth of a cultured mouse melanocyte line, melan/​a, in 8 days (p < 0.01).
Piperine (1/​piperoylpiperidine), the main alkaloid from Piper nigrum fruit, also
significantly stimulated melan/​a cell growth. Both Piper nigrum extract and
piperine induced morphological alterations in melan/​a cells, with more and
longer dendrites observed. The augmentation of growth by piperine was
effectively inhibited by RO/​31/​8220, a selective protein kinase C (PKC)
inhibitor, suggesting that PKC signalling is involved in its activity. This is
the first full report on such an activity of black pepper and piperine.

PMID: 10575373 [PubMed /​ indexed for MEDLINE]

77: J Ethnopharmacol. 1998 Dec;63(3):201/​8.

Jamu Gendong, a kind of traditional medicine in Indonesia: the microbial
contamination of its raw materials and endproduct.

Limyati DA, Juniar BL.

Widya Mandala Catholic University, Surabaya, Indonesia.

An examination on the microbiological quality of seven kinds of Jamu Gendong
(JG) and their raw materials has been conducted according to the requirements of
microbial contamination in traditional medicine, issued by the Department of
Health of Indonesia in 1986. Samples of JG and their raw materials were taken
from producers in three districts of Surabaya. The samples were subject to the
following examinations: total plate count (TPC), MPN coliform, the enumeration
of molds and yeasts, the presence or absence of Staphylococcus aureus,
Salmonella and Vibrio. Each time the JG samples were taken from different
producers together with their raw materials. The results of this investigation
showed that most of the JG samples were heavily contaminated with bacteria,
yeasts and molds. For bacteria, taken from the TPC results, their numbers were
ranging from 7.7 x 10(2) microorganisms/ml to too many to count (TMTC). For
yeasts and molds the numbers showed variations from 0 microorganisms/ml to TMTC.
Contamination with Coliform in 1 ml of JG were ranged from 0 to > 2.4 x 10(6)
microorganisms. In most of the samples pathogenic Staphylococci, Salmonella sp.
and Vibrio sp. were not detected, so that a conclusion can be drawn that most of
the contamination in JG are saprophytic, only a few pathogenic. The results also
show that it is possible to have JG which fulfill the government's requirements.
Similar results were obtained with the plant material constituents of JG such as
rhizomes, leaves, herbs and fruits of Piper nigrum and Piper retrofractum, with
the exception of Piper betle leaves and P. retrofractum fruits, both showing low
contamination of Coliform bacteria. However, the fruits of Citrus aurantifolia
and Morinda citrifolia were less contaminated, just like seeds of Oryza sativa,
Parkia roxburghii, bulbs of Allium sativum and the pulp of Tamarindus indica.
With these plant constituents of JG, it might be of interest to screen their
antibacterial and antifungal activities.

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

PMID: 10030724 [PubMed /​ indexed for MEDLINE]

78: J Ethnopharmacol. 1998 Aug;62(1):15/​24.

Influence of spices on the bacterial (enzyme) activity in experimental colon
cancer.

Nalini N, Sabitha K, Viswanathan P, Menon VP.

Department of Biochemistry, Annamalai University, Annamalainagar, Tamilnadu,
India.

In the presence of a known colon carcinogen, 1,2/​dimethyl hydrazine (DMH), the
activity of beta/​glucuronidase was found to be significantly increased in the
distal colon, distal intestine, liver and colon contents and the activity of
mucinase was increased in both the colon and fecal contents when compared to
control rats. Chilli (Capsicum annum L., Solanaceae) administration also showed
an increase when compared to control rats, whereas supplementation with cumin
(Cuminum cyminum L., Apiaceae) and black pepper (Piper nigrum L., Piperaceae) in
the presence of DMH, showed more or less similar values as that of the control
rats. The increase in beta/​glucuronidase activity may increase the hydrolysis of
glucuronide conjugates, liberating the toxins, while the increase in mucinase
activity may enhance the hydrolysis of the protective mucins in the colon. Thus
cumin and black pepper may protect the colon by decreasing the activity of
beta/​glucuronidase and mucinase. Histopathological studies also showed lesser
infiltration into the submucosa, fewer papillae and lesser changes in the
cytoplasm of the cells in the colon in cumin and black pepper groups when
compared to the DMH and chilli treated animals.

PMID: 9720607 [PubMed /​ indexed for MEDLINE]

79: Indian J Exp Biol. 1998 Jan;36(1):46/​50.

Permeability characteristics of piperine on oral absorption/​/​an active alkaloid
from peppers and a bioavailability enhancer.

Khajuria A, Zutshi U, Bedi KL.

Isotope Section, Regional Research Laboratory, Jammu/​Tawi, India.

Piperine, [1/​[5/​[1,3/​benzodioxol/​5/​yl]/​1/​oxo/​2,4, pentadienyl] piperidine], is a
pungent alkaloid present in Piper nigrum Linn, and P. longum Linn. It is shown
to enhance the bioavailability of various structurally and therapeutically
diverse drugs. A concise mechanism responsible for its bioavailability enhancing
action is poorly understood. This study is an effort to understand the
absorption dynamics of piperine in intestine on oral absorption. It encompasses
intestinal everted sacs as an experimental model. Cycloheximide treatment and
exclusion of Na+ salts from incubating medium were the variables used.
Absorption half life, absorption rate, absorption clearance and apparent
permeability co/​efficient were computed from the data. Experiments to denote
physico/​chemical characteristics of this moiety exhibited that it is a weak
base, highly lipophilic in nature with partial solubility in aqueous media. It
exhibited passive diffusion constituting non/​saturable absorption kinetics.
Transport of piperine was not resisted by UWL and was proposed to be absorbed
through transcellular pathway. It displayed short absorption clearance and high
apparent permeability co/​efficient. Data thus obtained suggested that piperine
is absorbed very fast across the intestinal barrier. It may act as an apolar
molecule and form apolar complex with drugs and solutes. It may modulate
membrane dynamics due to its easy partitioning thus helping in efficient
permeability across the barriers.

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

PMID: 9536651 [PubMed /​ indexed for MEDLINE]

80: Mycopathologia. 1996;134(2):109/​14.

High incidence of Aspergillus flavus and aflatoxins in stored groundnut in Ghana
and the use of a microbial assay to assess the inhibitory effects of plant
extracts on aflatoxin synthesis.

Awuah RT, Kpodo KA.

Department of Crop Science, University of Science and Technology, Kumasi, Ghana.

Groundnut samples from 21 selected markets in the 10 regions of Ghana yielded
high levels of the aflatoxigenic fungus Aspergillus flavus on half/​strength
potato dextrose agar. The fungus was associated with 31.7 and 12.8%,
respectively, of all damaged and undamaged kernels assayed. Only 0.24% of total
kernels assayed yielded A. parasiticus. Other fungi detected from total kernels
assayed were A. niger (34%), A. candidus (1.45%), A. tamarii (3.93%), A.
ochraceous (5.26%), Fusarium spp. (1.7%) Penicillium spp. (5.19%), a Mucor sp.
(2.3%), a Trichoderma sp. (0.2%), Rhizopus stolonifer (12%) and certain
unidentifiable fungi (11.72%). Total aflatoxin levels ranging from 5.7 to 22,
168 ppb were identified with damaged kernel samples. The mycotoxin was not
detected in 50% of undamaged kernel samples tested and very low levels mostly
ranging from 0.1 to 12.2 ppb were associated with the undamaged samples that
tested positive for aflatoxins. In a novel in vitro microbial assay to determine
the effectiveness of certain plant extracts against aflatoxin synthesis,
extracts from Xylopia aethiopica, Monodera myristica, Cinnamomum verum and Piper
nigrum permitted fungal growth in 1.5% potato/​dextrose broth while completely
suppressing NOR formation. These extracts, however, could not suppress NOR
formation in a yeast extract sucrose medium.

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

PMID: 8981776 [PubMed /​ indexed for MEDLINE]

81: Yakushigaku Zasshi. 1995;30(1):46/​53.

[Studies on the crude drugs used for the folk medicine described in
"mimi/​bukuro"]

[Article in Japanese]

Hamada T.

Kumamoto Institute of Technology.

"Mimi/​bukuro" is a book written by Moriyasu Negishi in the Edo period. M.
Negishi (1737/​1815) was a magistrate in the town of Edo. He was very much
interested in listening and recording many kinds of stories, which were told by
the various kinds of people, such as public officers, samurais, merchants,
doctors, etc. Among the stories of this book, some stories were found concerning
folk medicine, medicinal substance and charms. In this report, I studied the
medicines which were used in these stories. The medicines originated from
zoological, botanical and mineral substances. As the results of my studies,
there were zoological, botanical and mineral medicines were 13, 36 and 4
species, respectively. The examples of such medicines were as follows.
Zoological samples: Felis catus, Gallus gallus domesticus, Anguilla japonica and
Rapana venosa. Botanical samples: Artemisia princeps, Nicotiana tabacum, Panax
ginseng, Terminaria chebula and Piper nigrum.

Publication Types:
Biography
English Abstract
Historical Article

Personal Name as Subject:
Negishi M

PMID: 11613523 [PubMed /​ indexed for MEDLINE]

82: Plant Foods Hum Nutr. 1994 Oct;46(3):187/​93.

Influence of spices on protein utilisation of winged bean (Psophocarpus
tetragonolobus) and horsegram (Dolichos biflorus).

Pradeep KU, Geervani P.

Postgraduate & Research Centre, Faculty of Home Science, A.P. Agricultural
University, Hyderabad, India.

The influence of a mixture of eleven spices commonly consumed in India on the
utilisation of protein from boiled winged bean (Psophocarpus tetragonolobus) and
horsegram (Dolichos biflorus) was studied at 10 and 20 percent level of protein
intake in experimental rats. Spices used in the mixture include red chillies
(Capsicum annum), black pepper (Piper nigrum), coriander (Coriandrum sativum),
cumin (Cuminum cyminum), garlic (Allium sativum), ajowan (Carum copticum),
turmeric (Curcuma longa), caraway seeds (Carum carui) and fennel seeds
(Foeniculum vulgare). Addition of this spice mixture at 1.5% level of the diet
decreased the TD of both legumes, significantly only in the case of horsegram. A
significant increase was observed in the BV of both the legumes at both levels
of protein tested.

PMID: 7855088 [PubMed /​ indexed for MEDLINE]

83: Life Sci. 1994;55(5):389/​97.

Resiniferatoxin and piperine: capsaicin/​like stimulators of oxygen uptake in the
perfused rat hindlimb.

Eldershaw TP, Colquhoun EQ, Bennett KL, Dora KA, Clark MG.

Department of Biochemistry, University of Tasmania, Hobart, Australia.

The naturally occurring capsaicin/​like molecules, resiniferatoxin (RTX,
Euphorbia spp.) and piperine (Piper nigrum), each stimulated oxygen uptake (VO2)
in association with increased vascular resistance in a concentration/​dependent
manner when infused into the perfused rat hindlimb. 5 microM glyceryl trinitrate
(GTN, a nitrovasodilator) significantly blocked the oxygen and pressure
responses to both RTX and piperine, indicating a close relationship between
changes in VO2 and the vasoconstriction. Concentrations greater than those
required for maximal VO2 resulted in an inhibition of VO2, although perfusion
pressure continued to increase. Time course studies showed that both RTX and
piperine at high doses resulted in a tri/​phasic response. An initial phase of
transient VO2 stimulation was followed by a second phase of inhibition. A third
phase involving an often larger but transient stimulation of VO2 followed
removal of the agents and continued after the pressure returned to basal. The
actions of RTX and piperine were similar to those of other active capsaicin/​like
molecules tested previously in this system, including capsaicinoids (Capsicum
spp.), gingerols (Zingiber officinale), and shogoals (Zingiber officinale). RTX
was the most potent, and piperine the least potent of this series. Although
receptor involvement has yet to be unequivocally established, the data are
consistent with the presence of a functional capsaicin/​like (vanilloid) receptor
in the vasculature of the rat hindlimb that mediates vasoconstriction and oxygen
uptake. These findings may have implications for the future development of
thermogenic agents.

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

PMID: 8035653 [PubMed /​ indexed for MEDLINE]

84: Am J Chin Med. 1994;22(2):169/​74.

Antibacterial activity of alimentary plants against Staphylococcus aureus
growth.

Perez C, Anesini C.

Catedra de Farmacologia, Facultad de Odontologia, Universidad de Buenos Aires,
Argentina.

Alimentary plants were screened for antibacterial activity against a penicillin
G resistant strain of Staphylococcus aureus. Twenty/​five samples of plant
material corresponding to 21 species from 13 families were used. Both aqueous
and ethanol extracts were obtained from them. Antibacterial activity was
determined by the agar/​well diffusion method, using cephazolin as a standard
antibiotic. Seventeen ethanol extracts were found active. Eugenia caryophyllata
(clavo de olor*) flowers, Myristica fragans (nuez moscada*) seeds, Theobroma
cacao (cacao*) seed bark, Triticum sp (trigo*) fruit, Zea mays (maiz*) fruit and
Piper nigrum (pimienta*) ripe fruit produced some of the more active extracts (*
= Argentine vulgar names).

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

PMID: 7992816 [PubMed /​ indexed for MEDLINE]

85: Planta Med. 1993 Oct;59(5):413/​7.

Evaluation of the liver protective potential of piperine, an active principle of
black and long peppers.

Koul IB, Kapil A.

Department of Pharmacology, Regional Research Laboratory, Jammu, India.

Piperine, an active alkaloidal constituent of the extract obtained from Piper
longum and Piper nigrum, was evaluated for its antihepatotoxic potential in
order to validate its use in traditional therapeutic formulations. This plant
principle exerted a significant protection against tert/​butyl hydroperoxide and
carbon tetrachloride hepatotoxicity by reducing both in vitro and in vivo lipid
peroxidation, enzymatic leakage of GPT and AP, and by preventing the depletion
of GSH and total thiols in the intoxicated mice. Silymarin, a known
hepatoprotective drug was tested simultaneously for comparison. Piperine showed
a lower hepatoprotective potency than silymarin.

PMID: 8255933 [PubMed /​ indexed for MEDLINE]

86: Plant Foods Hum Nutr. 1993 Sep;44(2):137/​48.

Common Indian spices: nutrient composition, consumption and contribution to
dietary value.

Uma Pradeep K, Geervani P, Eggum BO.

Foods and Nutrition Department, Postgraduate & Research Centre (Home Sicence)
A.P. Agricultural University, Hyderabad, India.

Nutrient composition of eight commonly consumed spices of South India was
analysed. Spices analysed were red chillies (Capsicum annum), black pepper
(Piper nigrum), coriander seeds (Coriandrum sativum), cumin seeds (Cuminum
cyminum), garlic (Allium sativum), asafoetida (Ferula foetida), dry ginger
(Zingiber officinale) and ajowan (Carum copticum). The nutrients analysed were
proximate principles, minerals, starch, sugars, dietary fibre components,
tannins, phytic acid, enzyme inhibitors and amino acids. Dry ginger, ajowan and
asafoetida had high calcium (1.0/​1.5%) and iron (54/​62 mg/100 g) levels. The
tannin content of spices was also high (0.9/​1.3% DM). Dietary fibre ranged from
14/​53%. Spices had appreciable amounts of essential amino acids like lysine and
threonine. A survey revealed the average per capita consumption of spices to be
9.54 g and at that level, the nutrient contribution from spices ranged from 1.2
to 7.9% of an average adult Indian male's requirement for different nutrients.

PMID: 8397396 [PubMed /​ indexed for MEDLINE]

87: Cancer Lett. 1993 Aug 16;72(1/​2):5/​9.

Evaluation of the modulatory influence of black pepper (Piper nigrum, L.) on the
hepatic detoxication system.

Singh A, Rao AR.

Cancer Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University,
New Delhi, India.

The present paper assesses the modifying potential of black pepper on the
hepatic biotransformation system in mice. The modulatory effect was assessed on
glutathione S/​transferase (GST), cytochrome b5 (cyt. b5), cytochrome P/​450 (cyt.
P/​450), acid/​soluble sulfhydryl (/​SH) content and malondialdehyde (MDA) level.
Swiss albino mice of either sex (eight weeks old) were fed on a diet containing
0.5%, 1% and 2% black pepper (w/w) for 10 and 20 days. The findings revealed a
significant and dose/​dependent increase in GST and /​SH content in the
experimental groups except the one maintained on 0.5% black pepper diet for 10
days. Elevated levels of cyt. b5 and cyt. P/​450 were also statistically
significant and dose/​dependent. The level of MDA was lowered in the group fed on
2% black pepper diet for 20 days. Being a potential inducer of detoxication
system, the possible chemopreventive role of black pepper in chemical
carcinogenesis is suggested.

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

PMID: 8402574 [PubMed /​ indexed for MEDLINE]

88: Exp Toxicol Pathol. 1992 Apr;44(2):61/​5.

Carcinogenicity testing of some constituents of black pepper (Piper nigrum).

Wrba H, el/​Mofty MM, Schwaireb MH, Dutter A.

Vienna University, Institute of Applied and Experimental Oncology, Austria.

In mice, injection of safrole, tannic acid or methylcholanthrene (MCA) during
the preweaning period induced tumors in different organs. Safrole and tannic
acid (constituents of black pepper) were weak carcinogens when compared with MCA
which was used as a carcinogenic control substance. Force feeding of d/​limonene
(one of the pepper terpenoids) for a long time to the mice which were injected
with any of the above 3 substances reduced their carcinogenic activity, while
force feeding of piperine (one of black pepper alkaloids) was ineffective.

PMID: 1617288 [PubMed /​ indexed for MEDLINE]

89: Biochem Pharmacol. 1992 Apr 1;43(7):1401/​7.

Piperine/​mediated changes in the permeability of rat intestinal epithelial
cells. The status of gamma/​glutamyl transpeptidase activity, uptake of amino
acids and lipid peroxidation.

Johri RK, Thusu N, Khajuria A, Zutshi U.

Regional Research Laboratory (CSIR), Jammu/​Tawi, India.

The effect of piperine
(1/​[5/​(1,3/​benzodioxol/​5/​yl)/​1/​oxo/​2,4/​pentadienyl]piperidin e), (from Piper
nigrum) on the absorptive function of the intestine was studied. In vitro
experiments showed that piperine (25/​100 microM) significantly stimulated
gamma/​glutamyl transpeptidase (gamma/​GT, EC 2.3.2.2.) activity, enhanced the
uptake of radiolabelled L/​leucine, L/​isoleucine and L/​valine, and increased
lipid peroxidation in freshly isolated epithelial cells of rat jejunum. The
kinetic behaviour of gamma/​GT towards substrate and acceptor altered in the
presence of piperine. In the presence of benzyl alcohol, an enhanced gamma/​GT
activity due to piperine was maintained. These results suggested that piperine
may interact with the lipid environment to produce effects which lead to
increased permeability of the intestinal cells.

PMID: 1348936 [PubMed /​ indexed for MEDLINE]

90: Plant Foods Hum Nutr. 1991 Jul;41(3):269/​76.

Influence of spices on utilization of sorghum and chickpea protein.

Pradeep KU, Geervani P, Eggum BO.

Post Graduate and Research Centre, Home Science Faculty, A.P. Agricultural
University, Hyderabad, India.

Influence of eight common Indian spices on the protein quality of sorghum and
chickpea was studied. Spices used include red chillies (Capsicum annum), black
pepper (piper nigrum), coriander seeds (Coriandrum sativum) cumin seeds (Cuminum
cyminum), garlic (Allium sativum), asafoetida (Ferula foetida), dry ginger
(Zingiber officinale) and ajowan (Carum copticum). Addition of spices did not
affect protein digestibility (TD) of sorghum. The BV of all sorghum diets with
spices was higher than that of control diet. However, it was significant only in
case of diets combined with red chilli + coriander (1:1) mix, black pepper +
cumin (1:1) mix, coriander and cumin. Addition of spices did not have any effect
on TD or BV of chickpea diets.

PMID: 1924191 [PubMed /​ indexed for MEDLINE]

91: Oncology. 1991;48(4):347/​50.

Carcinogenic effect of force/​feeding an extract of black pepper (Piper nigrum)
in Egyptian toads (Bufo regularis).

el/​Mofty MM, Khudoley VV, Shwaireb MH.

Department of Zoology, Faculty of Science, University of Alexandria, Egypt.

50 male and 50 female Bufo regularis were treated, by force/​feeding, with an
extract of black pepper, at a dose level of 2 mg, 3 times a week for 5 months.
The first tumors appeared after 2 months. Liver tumors (hepatocellular
carcinomas, lymphosarcomas and fibrosarcomas) were found in 12 males and 18
females. Metastatic deposits of hepatocellular carcinomas were registered in the
spleen, kidney, fat body and ovary.

PMID: 1891179 [PubMed /​ indexed for MEDLINE]

92: Jpn J Med Sci Biol. 1990 Jun;43(3):95/​100.

Anti/​inflammatory activity of piperine.

Mujumdar AM, Dhuley JN, Deshmukh VK, Raman PH, Naik SR.

Research & Development Division, Hindustan Antibiotics Limited, Pimpri, Pune,
India.

Piperine (1/​peperoyl piperidine) was isolated from Piper nigrum Linn for the
evaluation of anti/​inflammatory activity in rats. Different acute and chronic
experimental models like carrageenin/​induced rat paw edema, cotton pellet
granuloma, and croton oil/​induced granuloma pouch, were employed.
Simultaneously, biochemical estimations were made to elucidate the underlying
mechanism of the action. Piperine acted significantly on early acute changes in
inflammatory processes and chronic granulative changes. It also acted partially
through stimulation of pituitary adrenal axis. Exudative changes in both acute
and chronic models, however, were insignificant.

PMID: 2283727 [PubMed /​ indexed for MEDLINE]

93: Indian J Exp Biol. 1990 May;28(5):486/​7.

Effect of piperine on pentobarbitone induced hypnosis in rats.

Mujumdar AM, Dhuley JN, Deshmukh VK, Raman PH, Thorat SL, Naik SR.

Laboratory of Pharmacology and Toxicology, Hindustan Antibiotics Ltd, Pimpri,
Pune, India.

Piperine (1/​peperoyl piperidine), a major alkaloid isolated from Piper nigrum
Linn, potentiated pentobarbitone sleeping time in dose dependant manner, with
peak effect at 30 min. Blood and brain pentobarbitone levels were higher in
piperine treated animals. Piperine treatment in rats, treated chronically with
phenobarbitone, significantly potentiated pentobarbitone sleeping time, as
compared to the controls. There was no alteration in barbital sodium sleeping
time. It is possible that, piperine inhibits liver microsomal enzyme system and
thereby potentiates the pentobarbitone sleeping time.

PMID: 2401524 [PubMed /​ indexed for MEDLINE]

94: Exp Pathol. 1990;40(4):233/​8.

Carcinogenesis induced by black pepper (Piper nigrum) and modulated by vitamin
A.

Shwaireb MH, Wrba H, el/​Mofty MM, Dutter A.

Zoology Department, Faculty of Science, Alexandria University, Egypt.

Painting and feeding of mice with 2mg of an extract from black pepper on 3 days
a week for 3 months results in a significant increase of the number of
tumor/​bearing mice. Tumor incidence is reduced in those groups of experimental
animals receiving 5 or 10mg Vitamin A/​palmitate twice weekly for 3 months by
feeding or painting during and subsequent to application of pepper extract.
Feeding of mice with powder of black pepper in diet (50g/3kg food) has no impact
on carcinogenesis.

PMID: 2098270 [PubMed /​ indexed for MEDLINE]

95: Appl Environ Microbiol. 1988 Mar;54(3):842/​3.

Aflatoxin contamination of some common drug plants.

Roy AK, Sinha KK, Chourasia HK.

Medicinal Plants Research Laboratory, University Department of Botany,
Bhagalpur, India.

This paper deals with the natural occurrence of aflatoxins in some common drug
plants collected from storehouses in Bihar, India. Of 15 samples analyzed, 14
were aflatoxin positive. The highest level of aflatoxin contamination was
detected in the seeds of Piper nigrum (1.20 micrograms/g), followed by the level
detected in the seeds of Mucuna prurita (1.16 micrograms/g), and the lowest
level was detected in the bark of Acacia catechu (0.09 micrograms/g). Of 158
isolates of Aspergillus flavus obtained from as many samples of drug plants, 49
were found to be toxigenic. The amount of aflatoxin B1 elaborated by the
toxigenic isolates was in the range of 0.86 to 5.24 micrograms/ml of culture
filtrate.

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

PMID: 3132102 [PubMed /​ indexed for MEDLINE]

96: Oncology. 1988;45(3):247/​52.

Carcinogenicity testing of black pepper (Piper nigrum) using the Egyptian toad
(Bufo regularis) as a quick biological test animal.

el/​Mofty MM, Soliman AA, Abdel/​Gawad AF, Sakr SA, Shwaireb MH.

Zoology Department, Faculty of Science, Alexandria University, Egypt.

Milled black pepper (Piper nigrum) force/​fed to Egyptian toads as a suspension
in amphibian saline or injected subcutaneously in the dorsal lymph sac as an
ethanol extract, induced primary tumours in the liver and secondary tumours in
other organs (kidney and spleen). When applied to the skin of experimental
animals as an ethanol extract, black pepper induced primary tumours in the liver
and secondary tumours in the ileum and stomach. Tumours of the liver were
diagnosed as hepatocellular carcinomas and those of the other organs as
metastases of the primary liver tumours. It is speculated that one or more
constituents of black pepper may be responsible for tumour induction in the
organs of the Egyptian toad Bufo regularis.

PMID: 3368202 [PubMed /​ indexed for MEDLINE]

97: Nahrung. 1987;31(9):913/​6.

Effect of black pepper and piperine on bile secretion and composition in rats.

Ganesh Bhat B, Chandrasekhara N.

Central Food Technological Research Institute, Mysore, India.

The influence of black pepper (Piper nigrum L.) and its active principle,
piperine on the secretion and composition of bile was investigated in the rat.
They were administered by gavage (black pepper at 250 or 500 mg and piperine at
12.5 or 25 mg/kg body wt.) or fed in the diet for 4 weeks (black pepper at 0.2
and 0.4%, piperine at 0.01 and 0.02%). The lower dose by gavage of black pepper
caused an increase in bile solids while with other treatments bile secretion or
dry matter in bile was not changed. Dietary feeding of black pepper caused an
increase in bile flow with a concomitant decrease in bile solids /​/​ a
hydrocholagoguic effect. Cholesterol and bile acid output were not affected by
black pepper or piperine at either level irrespective of the mode of
administration; in contrast, the secretion of uronic acids in bile was enhanced
by both levels of pepper as also of piperine indicating possible excretion of
some of the components of black pepper or of piperine as glucuronides.

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

PMID: 3431580 [PubMed /​ indexed for MEDLINE]

98: Environ Health Perspect. 1986 Aug;67:135/​42.

Chemical constituents of peppers (Piper spp.) and application to food
preservation: naturally occurring antioxidative compounds.

Nakatani N, Inatani R, Ohta H, Nishioka A.

In a structure analysis of the compounds of the genus Piper (Family Piperaceae),
we identified five phenolic amides from Piper nigrum, seven compounds from P.
retrofractum, and two compounds from P. baccatum. All the phenolic amides
possess significant antioxidant activities that are more effective than the
naturally occurring antioxidant, alpha/​tocopherol. One amide, feruperine, has
antioxidant activity as high as the synthetic antioxidants, butylated
hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). Naturally occurring
antioxidants, therefore, may surpass BHA and BHT in their ability to inactivate
mutagens in food.

PMID: 3757949 [PubMed /​ indexed for MEDLINE]

99: Ann Pharm Fr. 1985;43(1):15/​21.

[Decontamination of spices by ethylene oxide. The case of cloves (Eugenia
caryophyllus Spreng.) and white pepper (Piper nigrum L.)]

[Article in French]

Muraz B, Chaigneau M.

Publication Types:
English Abstract

PMID: 4062177 [PubMed /​ indexed for MEDLINE]

100: J Chromatogr. 1983 Jul 15;264(2):316/​20.

Determination of piperine in pepper (Piper nigrum) using high/​performance liquid
chromatography.

Rathnawathie M, Buckle KA.

PMID: 6885950 [PubMed /​ indexed for MEDLINE]

101: Int J Crude Drug Res. 1982 Nov;20(3):133/​7.

Folklore information from Assam for family planning and birth control.

Tiwari KC, Majumder R, Bhattacharjee S.

PIP: The author collected folklore information on herbal treatments to control
fertility from different parts of Assam, India. Temporary methods of birth
control include Cissampelos pareira L. in combination with Piper nigrum L., root
of Mimosa pudica L. and Hibiscus rosa/​sinensis L. Plants used for permanent
sterilization include Plumbago zeylanica L., Heliotropium indicum L., Salmalia
malabrica, Hibiscus rosa/​sinensis L., Plumeria rubra L., Bambusa rundinacea.
Abortion is achieved through use of Osbeckia nepalensis or Carica papaya L. in
combination with resin from Ferula narthex Boiss. It is concluded that there is
tremendous scope for the collection of folklore about medicine, family planning
agents, and other treatments from Assam and surrounding areas. Such a project
requires proper understanding between the survey team and local people, tactful
behavior, and a significant amount of time. Monetary rewards can also be
helpful for obtaining information from potential respondents.

PMID: 12266264 [PubMed /​ indexed for MEDLINE]

102: Ann Nutr Aliment. 1977;31(4/​6):485/​8.

Incidence of aflatoxin/​potential contamination in Spanish sausages.

Guergue J, Ramirez C.

525 strains of moulds were isolated from 8 samples of red pepper (Capsicum
annuum) and from 3 samples of black pepper (Piper nigrum). These spices were
commonly added to the various kinds of spanish sausages, specially to the
spanish "chorizo". Of these 525 isolated moulds, 100 belonged to the Aspergillus
flavus group. 69 were isolated from red pepper and 31 from black pepper. Of
these strains, 28 strains isolated from red pepper were found positive in
producing aflatoxin B1 while only 8 of the strains isolated from black pepper
produced aflatoxin B1. 16 of the strains isolated from red pepper also produced
aflatoxin G1. After experimental contamination by these aflatoxicogenic strains
of moulds of various kinds of spanish sausages, and after drying them under
similar storage conditions used in the sausage industry, the presence of
aflatoxin were detected only on the skin but not in the meat of the sausage.

PMID: 613913 [PubMed /​ indexed for MEDLINE]

103: Planta Med. 1976 Oct;30(2):198/​200.

Occurrence of N/​isobutyl eicosa/​trans/​2/​trans/​4/​dienamide in Piper nigrum.

Raina ML, Dhar KL, Atal CK.

PMID: 981396 [PubMed /​ indexed for MEDLINE]

104: Rev Latinoam Microbiol. 1973 Jan/​Mar;15(1):19/​22.

Fungus flora of black and white pepper (Piper nigrum L.).

Moreno Martinez E, Christensen CM.

PMID: 4517377 [PubMed /​ indexed for MEDLINE]

105: Nature. 1964 Jun 13;202:1133.

TRANSMISSION BY SNAILS OF THE SPECIES OF PHYTOPHTHORA WHICH CAUSES FOOT ROT OF
PIPER NIGRUM L. IN SARAWAK.

TURNER GJ.

PMID: 14207224 [PubMed /​ OLDMEDLINE]


 

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