Sodium sulphite enhances RNA isolation and sensitivity of Cucumber mosaic virus
detection by RT/​PCR in black pepper.

Siju S, Madhubala R, Bhat AI.

Division of Crop Protection, Indian Institute of Spices Research, Calicut
673012, Kerala, India.

Isolation of intact high quality RNA suitable for RT/​PCR from black pepper is
greatly hindered by the presence of polyphenols and polysaccharides. These
compounds adversely affect the sensitivity of virus detection by RT/​PCR. The
present study evaluated the effect of sodium sulphite in enhancing RNA yield and
quality in a modified acid guanidium thiocyanate/​phenol/​chloroform (AGPC)
protocol. The results were compared with the standard AGPC method and RNeasy
Plant Mini Kit (Qiagen) for detection of Cucumber mosaic virus through RT/​PCR.
The addition of sodium sulphite in the extraction buffer increased the
sensitivity of virus detection. Higher sensitivity of detection (than obtained
from the kit) was seen when sodium sulphite was used at 0.5%. Similar levels of
sensitivity were also observed for the detection of Cucumber mosaic virus from
Piper longum.

PMID: 17275931 [PubMed /​ in process]

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: J Ethnopharmacol. 2007 Feb 12;109(3):406/​11. Epub 2006 Aug 15.

Postnatal development and reproductive performance of F(1) progeny exposed in
utero to an ayurvedic contraceptive: Pippaliyadi yoga.

Balasinor N, Bhan A, Paradkar NS, Shaikh A, Nandedkar TD, Bhutani KK,
Roy/​Chaudhury M.

National Institute for Research in Reproductive Health (ICMR), J.M. Street,
Parel, Mumbai 400012, Maharashtra, India.

Pippaliyadi yoga or pippaliyadi vati is an ayurvedic contraceptive used in India
since ancient times. It is a combination of powdered fruit berries of Embelia
ribes Burm.f. (Myrsinaceae), Piper longum L. (Piperaceae) and borax in equal
proportion. Though the contraceptive potential is known since ancient times, no
systematic developmental toxicity studies have been carried out. The present
study was carried out to evaluate the postnatal developmental toxicity and the
reproductive performance of the progeny exposed in utero to pippaliyadi.
Pippaliyadi yoga was obtained from National Institute for Pharmaceutical
Education and Research (NIPER), India and the developmental toxicity was studied
by administering three doses, viz. 140, 300 and 700mg/(kgday) to gravid females
from day 6 to day 16 of gestation. Pippaliyadi did not have any adverse
developmental effects with low doses, however, with the five times higher dose,
a decrease in body weight of the pups was observed. The reproductive performance
of the progeny born to mothers treated with pippaliyadi was not significantly
affected. The present study suggests that in utero exposure to pippaliyadi does
not have any adverse effect on the postnatal development and reproductive
performance of the F(1) progeny.

PMID: 17088035 [PubMed /​ in process]

4: J Ethnopharmacol. 2006 Dec 6;108(3):445/​9. Epub 2006 Jun 23.

HPLC assisted chemobiological standardization of alpha/​glucosidase/​I enzyme
inhibitory constituents from Piper longum Linn/​An Indian medicinal plant.

Pullela SV, Tiwari AK, Vanka US, Vummenthula A, Tatipaka HB, Dasari KR, Khan IA,
Janaswamy MR.

Natural Products Laboratory, Organic Division/​I, Indian Institute of Chemical
Technology, Hyderabad/​500 007, India.

Formulations of traditional medicines are usually made up of complex mixture of
herbs. However, effective quality control methods in order to select right
quality materials are lacking. Though Piper longum is a widely used herb in
several Ayurvedic formulations prescribed for various diseases, there is no
analytical method in the literature so far which can help in selecting the right
quality material with proper proportions of the active ingredients
(alpha/​glucosidase/​I enzyme inhibitory principles). We employed a systematic
bioassay guided fractionation method and isolated pipataline, pellitorine,
sesamin, brachystamide B and guineensine as active principles. A reversed/​phase
high/​performance liquid chromatography method was developed to quantify these
active principles in the plant material, which can serve as an effective quality
control tool. The separation was carried out using a Discovery HS F5 C/​18 (ODS)
column and the solvent system used was a gradient comprising of (A) acetonitrile
and (B) water with a flow rate of 1 ml/min. The detection was performed using a
PDA detector. Regression equation pertaining to all the bioactive isolates
revealed a linear relationship (r2 > 0.9995). The detection limits (S/N = 3)
ranged from 0.005 to 0.001 microg/ml. Of all the active isolates, sesamin was
identified to be present in maximum quantities (0.91%) where as brachystamide B
was found in minimum quantity (0.01%).

PMID: 16872768 [PubMed /​ in process]

5: J Vector Ecol. 2006 Jun;31(1):138/​44.

Larvicidal effect of pepper plants on Aedes aegypti (L.) (Diptera: Culicidae).

Chaithong U, Choochote W, Kamsuk K, Jitpakdi A, Tippawangkosol P, Chaiyasit D,
Champakaew D, Tuetun B, Pitasawat B.

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

Ethanolic extracts derived from three species of the Piperaceae (pepper) family,
Piper longum L., P. ribesoides Wall., and P. sarmentosum Roxb. ex Hunt., were
evaluated for efficacy against early 4th instar larvae of Aedes aegypti
mosquitoes using larvicidal bioassays. The highest larvicidal efficacy was
established from P. longum, followed by P. sarmentosum and P. ribesoides, with
LC50 values of 2.23, 4.06, and 8.13 ppm, respectively. Observations of
morphological alterations on treated 4th instar larvae revealed that most
organs, except anal papillae, had a normal structural appearance that was
similar to controls. Under light microscopy, the internal structures of anal
papillae in the treated larvae showed shrinkage, while the external features
were normal in appearance. Ultrastructural studies, however, clearly
demonstrated external destruction, with extensive damage and shrunken cuticle of
the anal papillae. The structural deformation of anal papillae probably led to
their dysfunction, which may be intrinsically associated with the death of the
larvae. This study affords some evidence regarding the action site of the pepper
extracts and suggests their potential in developing new types of larvicides used
for mosquito control.

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

PMID: 16859102 [PubMed /​ indexed for MEDLINE]

6: 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]

7: 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]

8: Parasitol Res. 2006 Nov;99(6):715/​21.

Essential oils as potential adulticides against two populations of Aedes
aegypti, the laboratory and natural field strains, in Chiang Mai province,
northern Thailand.

Chaiyasit D, Choochote W, Rattanachanpichai E, Chaithong U, Chaiwong P, Jitpakdi
A, Tippawangkosol P, Riyong D, Pitasawat B.

Department of Parasitology, Chiang Mai University, Chiang Mai 50200, Thailand.

Essential oils derived from five plant species, celery (Apium graveolens),
caraway (Carum carvi), zedoary (Curcuma zedoaria), long pepper (Piper longum),
and Chinese star anise (Illicium verum), were subjected to investigation of
adulticidal activity against mosquito vectors. Two populations of Aedes aegypti,
the laboratory and natural field strains, collected in Chiang Mai province,
northern Thailand were tested in pyrethroid/​susceptibility bioassays. The
results revealed that the natural field strain of A. aegypti was resistant to
permethrin, with mortality rates ranging from 51 to 66%. A mild susceptibility,
with mortality rates ranging from 82 to 88%, was observed in the natural field
strain of A. aegypti exposed to lambdacyhalothrin, which suggested that this
strain was tolerant and might be resistant to this insecticide. However,
laboratory/​reared A. aegypti exposed to discriminating dosages of permethrin and
lambdacyhalothrin induced 100% mortality in all cases, thus indicating complete
susceptibility of this strain to these insecticides. The adulticidal activity
determined by topical application revealed that all five essential oils exerted
a promising adulticidal efficacy against both laboratory and natural field
strains of A. aegypti. Although the laboratory strain was slightly more
susceptible to these essential oils than the natural field strain, no
statistically significant difference was observed. Moreover, comparison of the
adulticidal activity indicated that the performance of these essential oils
against the two strains of A. aegypti was similar. The highest potential was
established from caraway, followed by zedoary, celery, long pepper, and Chinese
star anise, with an LC(50) in the laboratory strain of 5.44, 5.94, 5.96, 6.21,
and 8.52 microg/mg female, respectively, and 5.54, 6.02, 6.14, 6.35, and 8.83
microg/mg female, respectively, in the field strain. These promising essential
oils are, therefore, an alternative in developing and producing mosquito
adulticides as an effective measure used in controlling and eradicating mosquito
vectors.

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

PMID: 16738885 [PubMed /​ in process]

9: Biol Pharm Bull. 2006 Apr;29(4):834/​7.

Melanogenesis stimulation in murine B16 melanoma cells by Kava (Piper
methysticum) rhizome extract and kavalactones.

Matsuda H, Hirata N, Kawaguchi Y, Naruto S, Takata T, Oyama M, Iinuma M, Kubo M.

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

Melanogenesis stimulation activity of aqueous ethanolic extracts obtained from
several different parts of five Piper species, namely Piper longum, P. kadsura,
P. methysticum, P. betle, and P. cubeba, were examined by using cultured murine
B16 melanoma cells. Among them, the extract of P. methysticum rhizome (Kava)
showed potent stimulatory effect on melanogenesis as well as P. nigrum leaf
extract. Activity/​guided fractionation of Kava extract led to the isolation of
two active kavalactones, yangonin (2) and 7,8/​epoxyyangonin (5), along with
three inactive kavalactones, 5,6/​dehydrokawain (1), (+)/​kawain (3) and
(+)/​methysticin (4), and a glucosylsterol, daucosterin (6). 7,8/​Epoxyyangonin
(5) showed a significant stimulatory effect on melanogenesis in B16 melanoma
cells. Yangonin (2) exhibited a weak melanogenesis stimulation activity.

PMID: 16595931 [PubMed /​ indexed for MEDLINE]

10: Rev Inst Med Trop Sao Paulo. 2006 Jan/​Feb;48(1):33/​7. Epub 2006 Mar 9.

Adulticidal activity against Stegomyia aegypti (Diptera: Culicidae) of three
Piper spp.

Choochote W, Chaithong U, Kamsuk K, Rattanachanpichai E, Jitpakdi A,
Tippawangkosol P, Chaiyasit D, Champakaew D, Tuetun B, Pitasawat B.

Department of Parasitology, Faculty of Medicine, Chiang Mai University, Chiang
Mai 50200, Thailand. wchoocho@mail.med.cmu.ac.th

Three Piper species, Piper longum, P. ribesoides and P. sarmentosum, were
selected for investigation of adulticidal potential against Stegomyia aegypti, a
main vector of dengue and dengue haemorrhagic fever. Successive extraction by
maceration with 95% ethanol showed percentage yields of ethanolic extracts,
which derived from P. longum, P. ribesoides and P. sarmentosum, of 8.89, 3.21
and 5.30% (w/w), respectively. All Piper extracts illustrated an impressive
adulticidal activity when tested against female mosquitoes by topical
application. The susceptibility of St. aegypti females to ethanol/​extracted
Piper was dose dependent and varied among the plant species. The highest
adulticidal effect was established from P. sarmentosum, followed by P.
ribesoides and P. longum, with LD50 values of 0.14, 0.15 and 0.26 microg/female,
respectively. The potential of these Piper species, as possible mosquitocides,
established convincing activity for further researches to develop natural
substances for combat against adult mosquitoes.

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

PMID: 16547577 [PubMed /​ indexed for MEDLINE]

11: Int Immunopharmacol. 2006 May;6(5):733/​41. Epub 2005 Dec 19.

Piper longum inhibits VEGF and proinflammatory cytokines and tumor/​induced
angiogenesis in C57BL/6 mice.

Sunila ES, Kuttan G.

Department of Immunology, Amala Cancer Research Centre, Amala Nagar, Thrissur
680 555, Kerala, India.

The antiangiogenic activity of Piper longum was studied using in vivo as well as
in vitro models. In vivo, antiangiogenic activity was studied using B16F/​10
melanoma cell/​induced capillary formation in C57BL/6 mice. Intraperitoneal
administration of the extract (10 mg/dose/animal) significantly inhibited
(50.6%) the number of tumor/​directed capillaries induced by injecting B16F/​10
melanoma cells on the ventral side of C57BL/6 mice. The cytokine profile in the
serum of these animals showed a drastically increased level of proinflammatory
cytokines such as IL/​1beta, IL/​6, TNF/​alpha, GM/​CSF and the direct endothelial
cell proliferating agent, VEGF. Administration of the methanolic extract of P.
longum could differentially regulate the level of these cytokines. The level of
IL/​2 and tissue inhibitor of metalloprotease/​1 (TIMP/​1) was increased
significantly when the angiogenesis/​induced animals were treated with the
extract. The extract of P. longum at non/​toxic concentrations (10 microg/ml, 5
microg/ml, 1 microg/ml) inhibited the VEGF/​induced vessel sprouting in rat
aortic ring assay. Moreover, P. longum was able to inhibit the VEGF/​induced
proliferation, cell migration and capillary/​like tube formation of primary
cultured human endothelial cells. Hence, the observed antiangiogenic activity of
the plant P. longum is related to the regulation of these cytokines and growth
factors in angiogenesis/​induced animals.

Publication Types:
In Vitro

PMID: 16546703 [PubMed /​ indexed for MEDLINE]

12: Phytomedicine. 2006 Feb;13(3):196/​8. Epub 2005 Jun 24.

Inhibition of CCl4/​induced liver fibrosis by Piper longum Linn.?

Christina AJ, Saraswathy GR, Robert SJ, Kothai R, Chidambaranathan N, Nalini G,
Therasal RL.

Department of Pharmacology, KM College of Pharmacy, Uthangudi, Madurai, Tamil
Nadu, India. tinatina38@rediffmail.com

This study was carried out to evaluate the antifibrotic effect of ethanol
extract of the fruits of Indian herb Piper longum Linn. Liver fibrosis was
induced in rats by CCl(4) administration. The extent of liver fibrosis was
assessed by measuring the level of liver hydroxy proline (HP) and serum enzyme
levels. Following CCl(4) administration HP was significantly increased and serum
enzyme levels were elevated. Treatment with the ethanol extract of Piper longum
Linn. reduced the HP and also the serum enzymes. The liver weight that increased
following CCl(4) administration due to the deposition of collagen was reduced by
the ethanol extract. Hence, it is concluded that this extract inhibits liver
fibrosis induced by CCl(4).

Publication Types:
Comparative Study

PMID: 16428029 [PubMed /​ indexed for MEDLINE]

13: Pigment Cell Res. 2006 Feb;19(1):90/​8.

Inhibitory effect of piperlonguminine on melanin production in melanoma B16 cell
line by downregulation of tyrosinase expression.

Kim KS, Kim JA, Eom SY, Lee SH, Min KR, Kim Y.

College of Pharmacy and Research Center for Bioresource and Health, Chungbuk
National University, Cheongju, Korea.

Tyrosinase is a key enzyme for melanin biosynthesis, and hyperpigmentation
disorders are associated with abnormal accumulation of melanin pigments, which
can be improved by treatment with depigmenting agents. In the present study,
piperlonguminine from Piper longum was discovered to inhibit melanin production
in melanoma B16 cells stimulated with alpha/​melanocyte stimulating hormone
(alpha/​MSH), 3/​isobutyl/​1/​methylxanthine or protoporphyrin IX, where the
compound exhibited stronger depigmenting efficacy than kojic acid. However,
piperlonguminine did not affect 1/​oleoyl/​2/​acetyl/​sn/​glycerol/​induced
melanogenesis and did not affect protein kinase C/​mediated melanin production.
Surprisingly, piperlonguminine did not inhibit the catalytic activity of
cell/​free tyrosinase from melanoma B16 cells but rather suppressed tyrosinase
mRNA expression. This effect was attributed to the inhibitory action of
piperlonguminine on alpha/​MSH/​induced signaling through cAMP to the cAMP
responsive element binding protein that in turn regulates the expression of the
microphthalmia/​associated transcription factor, a key activator of the
tyrosinase promoter. This study demonstrates that piperlonguminine is an
efficient depigmenting agent with a novel mechanism of action.

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

PMID: 16420250 [PubMed /​ indexed for MEDLINE]

14: Nat Prod Res. 2006 Mar;20(3):235/​9.

Antifertility activity of Piper longum Linn. in female rats.

Lakshmi V, Kumar R, Agarwal SK, Dhar JD.

Division of Medicinal Chemistry, Central Drug Research Institute, Lucknow/​226
001, India. vijailakshmi@rediff.com

The crude extract, its different fractions and the major pure compound from the
active fraction of the powdered fruits of Piper longum were studied for the
antifertility effect in female rats. The crude extract and its hexane fraction
exhibited 100 and 86% efficacy respectively (days 1/​7 post/​coitum (p.c.)
schedule). On the other hand, 1/​butanol soluble, 1/​butanol insoluble and
chloroform fractions were inactive.

PMID: 16401553 [PubMed /​ indexed for MEDLINE]

15: 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]

16: Biochemistry. 2005 Dec 6;44(48):15944/​52.

Novel aromatic ester from Piper longum and its analogues inhibit expression of
cell adhesion molecules on endothelial cells.

Kumar S, Arya P, Mukherjee C, Singh BK, Singh N, Parmar VS, Prasad AK, Ghosh B.

Molecular Immunogenetics Laboratory, Institute of Genomics and Integrative
Biology, Mall Road, Delhi 110 007, India.

We report here the isolation and characterization of two active principles,
ethyl 3',4',5'/​trimethoxycinnamate (1) and piperine (2), from the combined
hexane and chloroform extracts of Piper longum. Using primary human umbilical
vein endothelial cells, we evaluated the activities of compound 1 on
TNF/​alpha/​induced expression of cell adhesion molecules, viz., ICAM/​1, VCAM/​1,
and E/​selectin, which play key roles in controlling various inflammatory
diseases. Both compounds 1 and 2 inhibited the TNF/​alpha/​induced expression of
ICAM/​1 in a dose/​ and time/​dependent manner; however, the activity of ethyl
3',4',5'/​trimethoxycinnamate (1) was approximately 1.3 times higher than that of
piperine (2). As ethyl 3',4',5'/​trimethoxycinnamate (1) has been isolated for
the first time from a natural source, Piper longum, and it exhibited higher
activity, we carried out further studies on it. To correlate its cell adhesion
molecule inhibitory activity with its functional consequences, we showed that it
significantly blocked the adhesion of neutrophils to endothelium in a time/​ and
concentration/​dependent manner. Importantly, the inhibitory effect of cinnamate
1 was found to be reversible. To elucidate its structure/​function/​activity
relationship, we synthesized nine different analogues of ethyl
3',4',5'/​trimethoxycinnamate, i.e., compounds 3/​11, and compared the ICAM/​1
inhibitory activity of compound 1 with those of its synthetic analogues as well
as the corresponding acids 12/​15. The structure/​activity studies indicate that
the chain length of the alcohol moiety, substituents in the aromatic ring, and
alpha, beta/​double bond of the cinnamic acid ester have significant effects on
the inhibition of TNF/​alpha/​induced expression of ICAM/​1 on endothelial cells.
These findings have implications in developing compounds with a better
therapeutic index against various inflammatory diseases.

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

PMID: 16313198 [PubMed /​ indexed for MEDLINE]

17: Zhong Yao Cai. 2005 Jul;28(7):570/​4.

[Study on proliferation effect of extracts of Piper longum on mesenchymal stem
cells of rat bone marrow and the relationship to chemical functional groups]

[Article in Chinese]

Li X, Zhou J, Li H, Du S, Li Y, Huang L, Chen D.

Guangzhou University of Traditional Chinese Medicine, Guangzhou 510405.

OBJECTIVE: To observe the effect of volatile oil and aqueous soluable part of
Piper longum on proliferation of rat mesenchymal stem cell (MSC) and the
chemical functional groups. METHODS: Mesenchymal stem cells were dissociated
from rat bone marrow and marked by Brdu, and the expression of CD44, CD54 and
double label of Brdu and CD44. The growth of rat mesenchymal stem cell under
volatile oil and aqueous soluable part of Piper longum was observed by means of
cell viability measurement (MTT) and morphological observation and Brdu, PCNA
immunohistochemical methods. RESULTS: Volatile oil of Piper longum could promote
the cell viability of MSC and the number of Brdu, PCNA positive cell in
dose/​dependant. There was significant difference in comparision with control
groups, C = C(50.66%), /​OH(27.02%) and other functional groups in volatile oil
of Piper longum were determined by GC/​MS, but the aqueous soluable part of Piper
longum could not promote the proliferation of MSC. CONCLUSIONS: Volatile oil of
Piper longum which consists of C = C, /​OH, and other functional groups has
strong effect on enhancing proliferation of MSC.

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

PMID: 16252724 [PubMed /​ indexed for MEDLINE]

18: Fitoterapia. 2005 Dec;76(7/​8):649/​55. Epub 2005 Oct 21.

Protective effect of Piper longum fruit ethanolic extract on radiation induced
damages in mice: a preliminary study.

Sunila ES, Kuttan G.

Amala Cancer Research Centre, Trissur, India.

The radioprotective property of an ethanolic extract of Piper longum fruits
(EEPLF) was investigated in Swiss mice. The white blood cell (WBC) count in
irradiated control mice was drastically reduced to 1900 cells/mm3 on third day
but in treated animals the count was 2783.3 cells/mm3. The number of bone marrow
cells and alpha/​esterase positive cells was also enhanced by the EEPLF
administration (16.7 x 10(6) cells/femur and 946.5/4000 cells, respectively)
when compared to the radiation exposed control animals (12.2 x 10(6) cells/femur
and 693.5/4000 cells, respectively). EEPLF reduced the elevated levels of
glutathione pyruvate transaminase (GPT), alkaline phosphatase (ALP), and lipid
peroxidation (LPO) in liver and serum of radiation treated animals. The extract
administration also increased the reduced glutathione (GSH) production to offer
the radioprotection.

PMID: 16243448 [PubMed /​ indexed for MEDLINE]

19: J Vet Sci. 2005 Sep;6(3):197/​200.

Alteration of pharmacokinetics of oxytetracycline following oral administration
of Piper longum in hens.

Singh M, Varshneya C, Telang RS, Srivastava AK.

Department of Pharmacology and Toxicology, College of Veterinary & Animal
Sciences, CSK Himachal Pradesh Agricultural University, Himachal Pradesh, India.

The pharmacokinetic profile of orally administered oxytetracycline (10 mg/kg
body weight) was studied 7 days post oral treatment of Piper longum (15 mg
equivalent/kg) in White Leghorn hens (2/​2.8 kg). On the day 8, oxytetracycline
(OTC) was administered orally and blood samples were collected from the wing
vein in heparinised vials for plasma separation at 0 (pre/​treatment), 15, 30,
60, 120, 240, 360, 480 and 600 minutes post OTC administration. Plasma OTC
concentrations were determined by microbial assay technique using Bacillus
cereus var. mycoides (ATCC 11778) as test organism. The plasma levels of OTC
against time were adequately described by one compartment open model. The
pharmacokinetic data revealed that P.longum treated animals had significantly
higher area under curve (AUC), area under the first moment of plasma drug
concentration/​time curve (AUMC) and mean residential time (MRT). Prior treatment
of P.longum significantly reduced elimination rate constant(beta)and increased
elimination half life (t(1/2beta)). The total body clearance (Cl(B)) reduced by
21%whereas total duration of pharmacological effect (t(d)) increased by 29%. The
treatment with P. longum reduced loading and maintenance dose by 33.3 and 39%,
respectively.

Publication Types:
Comparative Study

PMID: 16131821 [PubMed /​ indexed for MEDLINE]

20: Chem Pharm Bull (Tokyo). 2005 Jul;53(7):832/​5.

Piperine from the fruits of Piper longum with inhibitory effect on monoamine
oxidase and antidepressant/​like activity.

Lee SA, Hong SS, Han XH, Hwang JS, Oh GJ, Lee KS, Lee MK, Hwang BY, Ro JS.

College of Pharmacy, Chungbuk National University, Cheongju, Korea.

A bioassay/​guided isolation of the ethanol extract from the fruits of Piper
longum yielded a known piperidine alkaloid, piperine, as a monoamine oxidase
(MAO) inhibitor. Piperine showed an inhibitory effect against MAO/​A (IC50 value:
20.9 microM) and MAO/​B (IC50 value: 7.0 microM). Kinetic analyses by a
Lineweaver/​Burk plot clearly indicated that piperine competitively inhibited
MAO/​A and MAO/​B with Ki values of 19.0+//​0.9 microM and 3.19+//​0.5 microM,
respectively. The inhibition by piperine was found to be reversible by dialysis
of the incubation mixture. In addition, the immobility times in the tail
suspension test were significantly reduced by piperine, similar to that of the
reference antidepressant fluoxetine, without accompanying changes in ambulation
when assessed in an open/​field. These results suggest that piperine possesses
potent antidepressant/​like properties that are mediated in part through the
inhibition of MAO activity, and therefore represent a promising
pharmacotherapeutic candidate as an antidepressant agent.

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

PMID: 15997146 [PubMed /​ indexed for MEDLINE]

21: 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]

22: 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]

23: J Ethnopharmacol. 2005 Apr 8;98(1/​2):67/​72.

The effects of extracts from anti/​diarrheic Thai medicinal plants on the in
vitro growth of the intestinal protozoa parasite: Blastocystis hominis.

Sawangjaroen N, Sawangjaroen K.

Department of Microbiology, Faculty of Science, Prince of Songkla University,
Hat Yai, Songkhla 90112, Thailand. nongyao.s@psu.ac.th

The activities of n/​hexane, dichloromethane and methanol extracts from five
anti/​diarrheic Thai medicinal plants, Acacia catechu (Fabaceae) resin,
Amaranthus spinosus (Amaranthaceae) whole plant, Brucea javanica (Simaroubaceae)
seed, Piper longum (Piperaceae) fruit and Quercus infectoria (Fagaceae) nut gall
were tested against the in vitro growth of fresh isolates of the intestinal
protozoan parasite, Blastocystis hominis. The extracts at concentrations that
ranged from 62.5 to 2000 microg/mL, were incubated with several isolates of
Blastocystis hominis for 48 h. The activities were classified as killed,
inhibited, moderately inhibited and not/​inhibited. Dichloromethane and methanol
extracts from the Brucea javanica seed and a methanol extract from Quercus
infectoria nut gall showed the highest activity. At a concentration of 2000
microg/mL, the three extracts killed 82, 75 and 67% of the Blastocystis hominis
samples tested and inhibited 94, 100 and 76% of them, respectively.
Metronidazole, used as a reference antiprotozoan drug, at a concentration of 40
microg/mL, killed 97% of the Blastocystis hominis isolates and inhibited all
samples tested at concentrations that ranged from 1.25 to 20 microg/mL.

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

PMID: 15763365 [PubMed /​ indexed for MEDLINE]

24: 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]

25: 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]

26: Planta Med. 2004 Dec;70(12):1115/​8.

Piperlonguminine from Piper longum with inhibitory effects on
alpha/​melanocyte/​stimulating hormone/​induced melanogenesis in melanoma B16
cells.

Min KR, Kim KS, Ro JS, Lee SH, Kim JA, Son JK, Kim Y.

College of Pharmacy and Research Center for Bioresource and Health, Chungbuk
National University, Chenogju, Korea.

Skin hyperpigmentations such as melasma, freckles and senile lentigines can be
subjectively treated by depigmenting agents. In our ongoing study to find
melanogenesis inhibitors from natural sources, Piper longum L (fruits,
Piperaceae) was discovered to have an inhibitory effect on
alpha/​melanocyte/​stimulating hormone (alpha/​MSH)/​induced melanogenesis in
melanoma B16 cells. Piperlonguminine has been identified as the melanogenesis
inhibitor from P. longum by activity/​guided extraction and isolation. The
compound showed dose/​dependent inhibitory effects with 85.1 +//​ 4.9% inhibition
at 25 microM, 62.1 +//​ 6.1% at 12.5 microM, 36.4 +//​ 4.6% at 6.3 microM and 18.4
+//​ 5.1% at 3.1 microM on alpha/​MSH/​induced melanogenesis, showing an IC50 value
of 9.6 microM. As a positive control, kojic acid exhibited an IC50 value of 44.6
microM on the melanogenesis. As to the mode of action, piperlonguminine showed
an inhibitory effect on alpha/​MSH/​induced tyrosinase synthesis, documented by
Western immunoblot analysis. However, piperlonguminine did not show an
inhibitory effect on tyrosinase activity or a direct depigmenting effect of
melanin.

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

PMID: 15643542 [PubMed /​ indexed for MEDLINE]

27: 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]

28: 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]

29: Indian J Exp Biol. 2003 Jun;41(6):649/​51.

Analgesic activity of Piper longum Linn. root.

Vedhanayaki G, Shastri GV, Kuruvilla A.

Department of Pharmacology, PSG Institute of Medical Sciences & Research,
Coimbatore 641 004, India.

Piper longum root, commonly called Kandantippili, is traditionally used to treat
rheumatism, insomnia, palsy and epilepsy. But a scientific study on its central
actions is not available. This study screens P. longum root for opioid type
analgesia using rat tail/​flick method and for NSAID type analgesia using
acetic/​acid writhing method. Pentazocine (ip) and ibuprofen (oral) are used as
respective drug controls. An aqueous suspension of P. longum root powder is
given orally to mice and rat in doses of 200, 400 and 800 mg/kg. The delay in
reaction time for thermal stimulus in rats and the number of writhings to
chemical stimulus in mice are determined in each group. The results are analysed
statistically. The 400 and 800 mg/kg doses of P. longum show significant NSAID
type of analgesia (P < 0.001). Both Ibuprofen (40 mg/kg) and P. longum (800
mg/kg) show 50% protection against writhing. The delay in reaction time to
thermal stimulus was less than 6% for different doses of P. longum as against
100% for pentazocine. This indicates that P. longum root has weak opioid but
potent NSAID type of analgesic activity.

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

PMID: 15266916 [PubMed /​ indexed for MEDLINE]

30: 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]

31: Planta Med. 2004 Jul;70(7):678/​9.

Guineensine, an Acyl/​CoA: cholesterol acyltransferase inhibitor, from the fruits
of Piper longum.

Lee SW, Rho MC, Nam JY, Lim EH, Kwon OE, Kim YH, Lee HS, Kim YK.

Laboratory of Lipid Metabolism, Korea Research Institute of Bioscience and
Biotechnology, 52 Oun/​dong, Yusong/​gu, Taejon 305/​333, Korea.

Bioactivity/​guided fractionations for ACAT inhibitor led to the isolation of
guineensine from the CHCl (3) extract of Piper longum. Its structure was
identified by spectroscopic means (IR, UV, MS and NMR). Guineensine inhibited
ACAT activity in a dose/​dependent manner with an IC (50) value of 3.12 micro M.

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

PMID: 15254860 [PubMed /​ indexed for MEDLINE]

32: J Chromatogr A. 2004 Jun 25;1040(2):193/​204.

Preparative isolation and purification of amides from the fruits of Piper longum
L. by upright counter/​current chromatography and reversed/​phase liquid
chromatography.

Wu S, Sun C, Pei S, Lu Y, Pan Y.

Department of Chemistry, Zhejiang University, Yuquan Campus, Hangzhou, Zhejiang
Province 310027, China.

A versatile counter/​current chromatography (CCC) with upright type/​J multilayer
coil planet centrifuge, named upright CCC, was applied to the isolation and
purification of amides from Piper longum L., which is widely used as an anodyne
and a treatment for stomach disease in China. After the saponification by KOH of
the ethanol extracts solution of 15 kg of crude drug "Piper Longi Fructus", the
fruits of P. longum L., the solution was extracted with light petroleum and 500
g of red crude oil was obtained. Using 2.5 g of red crude oil as sample, the
preparative upright CCC with a two/​phase system composed of light petroleum (bp
60/​90 degrees C)/​ethyl acetate/​tetrachloromethane/​methanol/​water (1:1:8:6:1,
v/v) was successfully performed, which yielded nine fractions. Then these
fractions were further purified by use of reversed/​phase liquid chromatography
(RPLC) with a glass column of 500 x 10 mm i.d. packed with reversed/​phase silica
gel. As a result, nine target amides with over 95% purity, i.e., 50 mg of
(2E,4E)/​N/​isobutyl/​eicosa/​2,4/​dienamide, 150 mg of
(2E,4E,14Z)/​N/​isobutyl/​eicosa/​2,4,14/​trienamide, 110 mg of
(2E,4E,12Z)/​N/​isobutyl/​ocatadeca/​2,4,12/​trienamide, 50 mg of guineensine, 60 mg
of pipernonaline, 75 mg of pellitorine, 63 mg of piperine, 45 mg of piperanine,
and 40 mg of piperlonguminine were isolated, respectively. Structures of all
compounds were identified by electrospray ionization MS, electron impact
ionization MS, one/​ and two/​dimensional NMR spectra.

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

PMID: 15230526 [PubMed /​ indexed for MEDLINE]

33: Nat Prod Res. 2004 Jun;18(3):247/​51.

Isolation and synthesis of isodihydropiperlonguminine.

Anuradha V, Srinivas PV, Rao JM.

Natural Products Laboratory, Organic Division/​I, Indian Institute of Chemical
Technology, Hyderabad/​/​500 007, India.

The hexane extract of dried fruits of Piper longum on fractionation afforded a
new alkamide, isodihydropiperlonguminine and two phenyl propanoic acid
derivatives. The structures of these compounds are established based on
spectroscopic evidence and synthesis.

PMID: 15143835 [PubMed /​ indexed for MEDLINE]

34: J Ethnopharmacol. 2004 Apr;91(2/​3):357/​60.

Effects of Piper longum fruit, Piper sarmentosum root and Quercus infectoria nut
gall on caecal amoebiasis in mice.

Sawangjaroen N, Sawangjaroen K, Poonpanang P.

Department of Microbiology, Faculty of Science, Prince of Songkla University,
Hatyai, Songkhla 90112, Thailand. snongyao@ratree.psu.ac.th

The anti/​amoebic effects of crude methanol extracts of Piper longum fruit, Piper
sarmentosum root and Quercus infectoria nut gall against Entamoeba histolytica
infecting the caecum of mice were studied. Caecal amoebiasis in mice was induced
by injection of Entamoeba histolytica trophozoites directly into the caecum. The
mice were then treated orally with the extract, a standard drug (metronidazole),
or vehicle p.o. for five consecutive days, beginning 24 h after the infection
and were examined on the sixth day. At a dose of 1000 mg/kg per day, the
extracts of Piper longum fruit, Piper sarmentosum root and Quercus infectoria
nut gall had a curative rate of 100, 40 and 26%, respectively. At a
concentration of 500 and 250 mg/kg/day, extract from Piper longum fruit was
still effective in 93 and 46% of the cases, respectively, while extract from
Piper sarmentosum root at a dose of less than 1000 mg/kg per day did not cure
any mice from amoebiasis. Extract of Quercus infectoria nut gall at a
concentration of 500 and of 250 mg/kg per day cured 26 and 13% of mice,
respectively. Metronidazole at a concentration of 125 and of 62.5 mg/kg per day
had a curative rate of 100 and 60%, respectively. The severity of caecal wall
ulceration was reduced in mice which received the extract and metronidazole as
compared to the control animals.

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

PMID: 15120461 [PubMed /​ indexed for MEDLINE]

35: 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]

36: J Ethnopharmacol. 2004 Feb;90(2/​3):339/​46.

Immunomodulatory and antitumor activity of Piper longum Linn. and piperine.

Sunila ES, Kuttan G.

Amala Cancer Research Centre, Amalanagar, Thrissur 680 553, Kerala, India.

Alcoholic extract of the fruits of the plant Piper longum and its component
piperine was studied for their immunomodulatory and antitumor activity.
Alcoholic extract of the fruits was 100% toxic at a concentration of 500
microg/ml to Dalton's lymphoma ascites (DLA) cells and 250 microg/ml to Ehrlich
ascites carcinoma (EAC) cells. Piperine was found to be cytotoxic towards DLA
and EAC cells at a concentration of 250 microg/ml. Alcoholic extract and
piperine was also found to produce cytotoxicity towards L929 cells in culture at
a concentration of 100 and 50 microg/ml, respectively. Administration of
alcoholic extract of Piper longum (10 mg/dose/animal) as well as piperine (1.14
mg/dose/animal) could inhibit the solid tumor development in mice induced with
DLA cells and increase the life span of mice bearing Ehrlich ascites carcinoma
tumor to 37.3 and 58.8%, respectively. Administration of Piper longum extract
and piperine increased the total WBC count to 142.8 and 138.9%, respectively, in
Balb/c mice. The number of plaque forming cells also enhanced significantly by
the administration of the extract (100.3%) and piperine (71.4%) on 5th day after
immunization. Bone marrow cellularity and alpha/​esterase positive cells were
also increased by the administration of Piper longum extract and piperine.

Publication Types:
Comparative Study

PMID: 15013199 [PubMed /​ indexed for MEDLINE]

37: J AOAC Int. 2003 Nov/​Dec;86(6):1124/​7.

Spectrophotometric method for estimation of alkaloids precipitable with
Dragendorff's reagent in plant materials.

Sreevidya N, Mehrotra S.

National Botanical Research Institute, 2, Rana Pratap Marg, Lucknow, India 226
001.

A rapid, easy, and simple spectrophotometric method was developed for the
estimation of total alkaloids precipitated by Dragendorff's reagent (DR) in
plant materials. It is based on the formation of yellow bismuth complex in
nitric acid medium with thiourea. The yellow/​colored complex formed obeys
Lambert/​Beer's law in the concentration range of 0.06/​50 microg/mL with
lambdamax at 435 nm. Using this method, the alkaloidal percentage of certain
alkaloids (ajamalicine, papaverine, cinchonine, piperine, berberine) and some
plant materials containing alkaloids (Berberis aristata, Solanum nigrum, and
Piper longum) were determined. The method was compared with other methods. It
can be used for routine analysis of commercial samples by industries dealing
with herbal drugs for standardization of plant materials containing alkaloids
and for alkaloid/​containing pharmaceutical products.

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

PMID: 14979692 [PubMed /​ indexed for MEDLINE]

38: 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]

39: Phytother Res. 2002 Nov;16(7):689/​91.

Potential antiamoebic property of the roots of Piper longum Linn.

Ghoshal S, Lakshmi V.

Division of Microbiology, Central Drug Research Institute, Lucknow /​ 226 001,
India.

In an earlier study we reported the effect of ethanol extracts of Piper longum
fruit against caecal amoebiasis in rats. A follow/​up study to determine whether
the roots possess similar antiamoebic activity was carried out. The ethanolic
extract of roots was amoebicidal at 1,000 microg/mL in vitro and cured 88% of
caecal amoebiasis cases, suggesting that both the root and fruit of P. longum
possess antiamoebic activity to approximately the same extent. Copyright 2002
John Wiley & Sons, Ltd.

PMID: 12410557 [PubMed /​ indexed for MEDLINE]

40: Fitoterapia. 2002 Oct;73(6):508/​10.

Brine shrimp lethality bioassay of selected Indian medicinal plants.

Padmaja R, Arun PC, Prashanth D, Deepak M, Amit A, Anjana M.

Bioassay Unit, Research & Development Centre, Natural Remedies Pvt Ltd, Plot No
5B, Veerasandra Indl Area, Hosur Road, Bangalore 561 229, India.

Ethanolic extracts of six Indian medicinal plants, piperine, guggulsterone E and
guggulsterone Z were tested for cytotoxicity using brine shrimp lethality test.
Piper longum showed most potent cytotoxic activity. Piperine, guggulsterone E
and guggulsterone Z showed potent activity with LC(50) 2.4, 8.9 and 4.9,
respectively. Copyright 2002 Elsevier Science B.V.

PMID: 12385875 [PubMed /​ indexed for MEDLINE]

41: 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]

42: J Agric Food Chem. 2002 Jun 19;50(13):3765/​7.

A piperidine amide extracted from Piper longum L. fruit shows activity against
Aedes aegypti mosquito larvae.

Yang YC, Lee SG, Lee HK, Kim MK, Lee SH, Lee HS.

Faculty of Biotechnology and Institute of Agricultural Science and Technology,
College of Agriculture, Chonbuk National University, Chonju 561/​756, South
Korea.

Mosquito larvicidal activity of Piper longum fruit/​derived materials against the
fourth/​instar larvae of Aedes aegypti was examined. A crude methanol extract of
P. longum fruits was found to be active against the larvae, and the hexane
fraction of the methanol extract showed a strong larvicidal activity of 100%
mortality. The biologically active component of P. longum fruits was
characterized as pipernonaline by spectroscopic analyses. The LC(50) value of
pipernonaline was 0.25 mg/L. The toxicity of pipernonaline is comparable to that
of pirimiphos/​methyl as a mosquito larvicide. In tests with available components
derived from P. longum, no activity was observed with piperettine, piperine, or
piperlongumine.

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

PMID: 12059157 [PubMed /​ indexed for MEDLINE]

43: 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]

44: J Biosci. 2001 Nov;26(4 Suppl):391/​405.

Current status of fertility control methods in India.

Sharma RS, Rajalakshmi M, Sharma RS, Jeyaraj DA.

Indian Council of Medical Research, Ansari Nagar, New Delhi 110 029, India.
radheyss@hotmail.com

Approximately 48.2% of couples of 15 to 49 years of age practice family planning
methods in India. Female sterilization accounts for 34.2%, with male
sterilization declining from 3.4% in 1992/​93 to 1.9% in 1998/​99. Use of the
condom increased to 3.1% from 2.4%. There is an urgent need for research to
develop new contraceptive modalities especially for men and also for women and
to make existing methods more safe, affordable and acceptable. Current efforts
in India to develop a male contraceptive are mainly directed towards (i)
development of antispermatogenic agents to suppress sperm production, (ii)
prevention of sperm maturation, (iii) prevention of sperm transport through vas
deferens or rendering these sperm infertile and (iv) prevention of sperm
deposition. Research work in the field of prevention of sperm transport through
vas deferens has made significant advances. Styrene maleic anhydride (SMA)
disturbed the electrical charge of spermatozoa leading to acrosome rupture and
consequent loss in fertilizing ability of sperm. A multicentre phase/​III
clinical trial using SMA is continuing and it is hoped that the SMA approach
would be available in the near future as an indigenously developed injectable
intra/​vasal male contraceptive. The safety and efficacy of available oral
contraceptives were evaluated. An indigenously developed oral contraceptive
'Centchorman', which is a nonsteroidal, weakly estrogenic but potently
antiestrogenic, was found to be safe and effective and is now being marketed in
India since 1991 as a 'once a week' pill. Cyclofem and Mesigyna have been
recommended as injectable contraceptives with proper counselling and service
delivery by Indian studies. It has been recommended that these injectable
contraceptives be added to the existing range of contraceptive methods available
in the National Family Planning Programme. Based on the Indian studies CuT 200
was also recommended. Studies have indicated the advantage of intrauterine
devices (IUD); they are long acting, relatively easily removed and fertility
returns rapidly after their removal. Recent studies have recommended CuT 200 for
use up to 5 years. The combination of some plant products i.e. Embelia ribes,
Borax and Piper longum has been found to be safe and effective as a female
contraceptive and the results of phase/​I clinical trials are encouraging.
Research work is going on in the country in various areas with special reference
to hormonal contraceptive /​ a three monthly injectable contraceptive,
immuno/​contraceptives, antiprogestins, etc.

Publication Types:
Review

PMID: 11779954 [PubMed /​ indexed for MEDLINE]

45: Eur J Nutr. 2001 Jun;40(3):127/​33.

Investigations on possible serotonergic involvement in effects of OB/​200G
(polyherbal preparation) on food intake in female mice.

Kaur G, Kulkarni SK.

Pharmacology Division, Univ Inst Pharm Sci, Panjab University, Chandigarh,
India.

BACKGROUND: OB/​200G is a polyherbal preparation containing aqueous extracts of
Garcinia cambogia, Gymnema sylvestre, Zingiber officinale, Piper longum and
resin from Commiphora mukul, all possessing thermogenic properties. Our previous
studies reveal OB/​200G to exert antiobesity effects in dietary animal models of
obesity. AIM OF THE STUDY: The present study investigated the possible
involvement of serotonergic system in the effect of OB/​200G on food intake. We
examined the effects of systemic pretreatment with 5/​HT depletor,
p/​chlorophenylalanine (PCPA, 300 mg/kg, i. p. for 6 days), 5/​HT1A agonist,
(8/​hydroxy/​2/​(di/​N/​propylamino)/​tetralin (8/​OH/​DPAT, 0.1 mg/kg, i. p.),
nonselective 5/​HT antagonist, cyproheptadine (1 mg/kg, i. p.), 5/​HT2 receptor
antagonist, seganserin (1 and 2 mg/kg, i. p.) and 2/​deoxy/​D/​glucose (2/​DG,
glucose antimetabolite, 500 mg/kg, i. p.) on satiety induced by OB/​200G (500
mg/kg, p. o.) in non/​deprived female mice. The results were compared with
fluoxetine (10 mg/kg, i. p.), a selective serotonin reuptake inhibitor. METHODS:
Fifteen minutes after the last drug administration, groups of mice were
presented with sweetened chow and the amount of food consumed was recorded at
0.5,1,2, 3 and 4h time intervals. RESULTS: The hyperphagic effect of PCPA,
8/​OH/​DPAT, cyproheptadine and 2/​DG was significantly (p < 0.05) antagonized by
both OB/​200G and fluoxetine. However, the anorectic effect of fluoxetine was not
reversed by centrally acting 5/​HT2 antagonist, seganserin but the latter
markedly attenuated the satiety action of OB/​200G. CONCLUSION: The present
observations suggest the role of serotonin in mediation of satiety by OB/​200G
and hence its antiobesity effect.

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

PMID: 11697445 [PubMed /​ indexed for MEDLINE]

46: Indian J Exp Biol. 2000 Oct;38(10):994/​8.

Effect of Piper longum Linn, Zingiber officianalis Linn and Ferula species on
gastric ulceration and secretion in rats.

Agrawal AK, Rao CV, Sairam K, Joshi VK, Goel RK.

Drayaguna Institute of Medical Sciences, Banaras Hindu University, Varanasi 221
005, India.

Use of Dipaniya Mahakasaya, a group consisting of 10 herbal drugs, has been
suggested in Charaka Samhita to improve digestion. Out of these 10 plants,
three, viz. P. longum (water decoction), Z. officianalis (water decoction) and
Ferula species (colloidal solution) were studied for their antiulcer and
mechanism of antiulcer effects in rats. All the drugs in the dose of 50 mg/kg,
p.o., 60 min prior to experiment, showed significant protection against gastric
ulcers induced by 2 hr cold restraint stress, aspirin (200 mg/kg, 4 hr) and 4 hr
pylorus ligation. The antiulcerogenic effect seemed to be due to the
augmentation of mucin secretion and decreased cell shedding rather than
offensive acid and pepsin secretion which however, were found to be increased by
them.

PMID: 11324171 [PubMed /​ indexed for MEDLINE]

47: Biochem Syst Ecol. 2001 May;29(5):537/​538.

Tetrahydropiperine, the first natural aryl pentanamide from Piper longum.

Madhusudhan P, Vandana KL.

Organic Chemistry Division /​I, Indian Institute of Chemical Technology, /​ 500
007, Hyderabad, India

PMID: 11274775 [PubMed /​ as supplied by publisher]

48: J Ethnopharmacol. 2001 Feb;74(2):189/​93.

Embryotoxicity and teratogenicity studies of an ayurvedic
contraceptive/​/​pippaliyadi vati.

Chaudhury MR, Chandrasekaran R, Mishra S.

Division of Toxicology, National Institute of Immunology, Aruna Asaf Ali Marg,
110067, New Delhi, India.

An ayurvedic contraceptive/​/​pippaliyadi vati, containing equal parts of powdered
seeds or fruit berries of Embelia ribes, fruit of Piper longum and borax powder
was fed orally to two groups of pregnant rats: 2.5 times to one and five times
to the other; the recommended dose for humans. The foetuses of mothers fed with
pippaliyadi had low birth weights and were smaller in length. The mothers gained
less weight during gestation. Developmental defects of soft tissues and
skeletons were analyzed. There were instances of herniation of the intestines
into the umbilical cord in foetuses of mothers who were administered
pippaliyadi. The control and the gum acacia groups did not show such herniation.

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

PMID: 11167037 [PubMed /​ indexed for MEDLINE]

49: J Am Mosq Control Assoc. 2000 Sep;16(3):245/​7.

Mosquito larvicidal activity of pipernonaline, a piperidine alkaloid derived
from long pepper, Piper longum.

Lee SE.

Plant Protection Research Unit, WRRC, USDA/​ARS, Albany, CA 94710, USA.

A methanol extract of Piper longum fruit was found to be active against mosquito
larvae of Culex pipiens pallens at 10 microg/ml after 24 h. A piperidine
alkaloid, pipernonaline, was found to be responsible for this activity, with the
24/​h median lethal dose (LD50) value for this compound being 0.21 mg/liter. The
LD50 value of pipernonaline was not much higher than those for the 3
organophosphorous insecticides malathion, chlorpyrifos/​methyl, and
pirimiphos/​methyl, used for comparative purpose in this study. Structural
elucidation of pipernonaline was by means of mass spectrometry (1H and 13C
nuclear magnetic resonance imaging).

Publication Types:
Comparative Study

PMID: 11081654 [PubMed /​ indexed for MEDLINE]

50: Phytother Res. 1999 Nov;13(7):561/​5.

Antigiardial and immunostimulatory effect of Piper longum on giardiasis due to
Giardia lamblia.

Tripathi DM, Gupta N, Lakshmi V, Saxena KC, Agrawal AK.

Division of Microbiology, Central Drug Research Institute, P.O. Box 173, Lucknow
/​ 226001, India.

Piper longum fruit, used in traditional remedies as well as in the Ayurvedic
system of medicine against intestinal disorders, was tested for its efficacy
against experimental infection of Giardia lamblia in mice. On in vitro test, an
aqueous extract of P. longum fruit powder (PF) at 250 microg/mL and its ethanol
extract at 125 microg/mL showed 100% giardicidal activity. A low order activity
was found in the n/​butanol extract. Further fractionation in hexane and
chloroform resulted in a total loss of activity. The survival of/​trophozoites in
mice at 900 mg/kg body weight was 11.12 in PF, 8. 54 in aqueous extract, 5.81 in
ethanol extract. The antigiardial activity of PF in hexane, chloroform and
n/​butanol soluble fractions was comparable to the drug/​untreated control
(47.63). Piper longum possessed a demonstrable immunostimulatory activity, both
specific and nonspecific, as evident from the standard test parameters such as
haemagglutination titre (HA), plaque forming cell (PFC) counts, macrophage
migration index (MMI) and phagocytic index (PI). A maximum effect was found at
225 mg/kg body weight in mice. The effect was marginally reduced at higher doses
of 450 and 900 mg/kg or the lower dose of 112.5 mg/kg. Copyright 1999 John Wiley
& Sons, Ltd.

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

PMID: 10548746 [PubMed /​ indexed for MEDLINE]

51: Phytother Res. 1999 Jun;13(4):275/​91.

Adaptogenic properties of six rasayana herbs used in Ayurvedic medicine.

Rege NN, Thatte UM, Dahanukar SA.

Ayurveda Research Centre, Department of Pharmacology and Therapeutics, Seth GS
Medical College, Parel, Mumbai, India. kemarc@bom3.vsnl.net.in

Plants from all over the world such as Eleutherococcus senticosus, Panax
ginseng, Raponticum carthamoides, Rhodiola rosea, Withania somnifera and Ocimum
sanctum have been extensively evaluated for their adaptogenic potential.
However, none of them has been successfully introduced as an adaptogen in the
clinic. This paper discusses some of the problems in evaluation of adaptogens
which have precluded their inclusion as clinically useful drugs. We further
discuss our results with six rasayana plants from Ayurveda, which were studied
for their adaptogenic potential. The whole, aqueous, standardized extracts of
selected plants (Tinospora cordifolia, Asparagus racemosus, Emblica officinalis,
Withania somnifera, Piper longum and Terminalia chebula) were administered
orally to experimental animals, in a dose extrapolated from the human dose,
following which they were exposed to a variety of biological, physical and
chemical stressors. These plants were found to offer protection against these
stressors, as judged by using markers of stress responses and objective
parameters for stress manifestations. Using a model of cisplatin induced
alterations in gastrointestinal motility, the ability of these plants to exert a
normalizing effect, irrespective of direction of pathological change was tested.
All the plants reversed the effects of cisplatin on gastric emptying, while
Tinospora cordifolia and Asparagus racemosus also normalized cisplatin induced
intestinal hypermotility. Tinospora cordifolia was also tested for its ability
to modulate the changes occurring in the phagocytic activity of peritoneal
macrophages after exposure of rats to either carbon tetrachloride or horse
serum. It was found to normalize the phagocytic function irrespective to the
direction of change, complying to the definition of an adaptogen. All the plant
drugs were found to be safe in both acute and subacute toxicity studies. Studies
on the mechanisms of action of the plants revealed that they all produced
immunostimulation. The protection offered by Tinospora cordifolia against stress
induced gastric mucosal damage was lost if macrophage activity was blocked.
Emblica officinalis strengthened the defence mechanisms against free radical
damage induced during stress. The effect of Emblica officinalis appeared to
depend on the ability of target tissues to synthesize prostaglandins. Recent
data obtained with Tinospora cordifolia suggest that it may induce genotypic
adaptation, further opening the arena for more research and experimentation.

Publication Types:
Review

PMID: 10404532 [PubMed /​ indexed for MEDLINE]

52: Plant Foods Hum Nutr. 1998;52(3):231/​9.

Toxicity studies in mice of common spices, Cinnamomum zeylanicum bark and Piper
longum fruits.

Shah AH, Al/​Shareef AH, Ageel AM, Qureshi S.

Central Laboratory for Drug and Food Analysis, M.O.H. Riyadh, Saudi Arabia.

Acute (24 hours) and chronic (90 days) oral toxicity studies on the ethanolic
extracts of common spices Cinnamomum zeylanicum Nees bark and Piper longum L.
fruits were carried out in mice. Acute dosages were 0.5, 1.0 and 3 g/kg while
the chronic dosage was 100 mg/kg/day. All external morphological, hematological
and spermatogenic changes, in addition to body weight and vital organ weights,
were recorded. The extracts of both the plants caused no significant acute or
chronic mortality compared to the control during this study. During chronic
treatment there was no significant change in the pre/​ and post treatment body
weight of the test animals while the weight gain in the control group was
significant. C. zeylanicum treatment caused reduction in liver weight while P.
longum caused a significant increase in the weight of the lungs and spleen of
the treated animals compared to the control. Hematological studies revealed a
significant fall in hemoglobin level of C. zeylanicum treated animals. Both of
the extracts induced a significant increase in reproductive organ weights, sperm
motility, sperm count and failed to illicit any spermatotoxic effect.

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

PMID: 9950084 [PubMed /​ indexed for MEDLINE]

53: J Ethnopharmacol. 1997 May;56(3):233/​6.

Management of giardiasis by a herbal drug 'Pippali Rasayana': a clinical study.

Agarwal AK, Tripathi DM, Sahai R, Gupta N, Saxena RP, Puri A, Singh M, Misra RN,
Dubey CB, Saxena KC.

Central Drug Research Institute, Division of Microbiology, Lucknow, India.

Pippali Rasayana (PR), an Indian ayurvedic drug prepared from Palash (Butea
monosperma (Lamk) Kuntze; Leguminaceae) and Pippali (Piper longum L.;
Piperaceae), was administered at a dose of 1 g p.o. three times daily for a
period of 15 days to patients (25 treated, 25 placebo controls) suffering from
giardiasis with clinical signs and symptoms, and stools positive for
trophozoites/cysts of Giardia lamblia. After 15 days of drug treatment there was
a complete disappearance of G. lamblia (trophozoites/cysts) from the stools of
23 out of 25 patients. General signs and symptoms of ill health and abdominal
discomfort, presence of mucus, pus cells and RBCs were significantly reduced.
There was a marked improvement in the clinical and haematological profile of the
patients. Spontaneous recovery in 20% cases was recorded in placebo controls.

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

PMID: 9201614 [PubMed /​ indexed for MEDLINE]

54: J Ethnopharmacol. 1996 Mar;50(3):167/​70.

Antiamoebic activity of Piper longum fruits against Entamoeba histolytica in
vitro and in vivo.

Ghoshal S, Prasad BN, Lakshmi V.

Division of Microbiology, Central Drug Research Institute, Lucknow, India.

The fruits of Piper longum used in traditional remedies against intestinal
distress have been tested for their efficacy against experimental caecal
amoebiasis of rats. The ethanolic extract, hexane fraction, n/​butanol soluble
fraction exerted in vitro amoebicidal action at 1000 micrograms/mL and the
chloroform fraction at 500 micrograms/mL. The ethanolic extract and piperine, a
pure compound, from this plant material cured 90% and 40% of rats with caecal
amoebiasis, respectively.

PMID: 8691851 [PubMed /​ indexed for MEDLINE]

55: J Ethnopharmacol. 1994 Dec;44(3):143/​6.

Management of giardiasis by an immuno/​modulatory herbal drug Pippali rasayana.

Agarwal AK, Singh M, Gupta N, Saxena R, Puri A, Verma AK, Saxena RP, Dubey CB,
Saxena KC.

Division of Biochemistry and Microbiology, Central Drug Research Institute,
Lucknow, India.

Pippali rasayana (PR), an Ayurvedic herbal medicine, prepared from Piper longum
(Pippali) and Butea monosperma (Palash), and prescribed for the treatment of
chronic dysentery and worm infestations was tested for anti/​giardial and
immuno/​stimulatory activity in mice, infected with Giardia lamblia trophozoites.
It produced up to 98% recovery from the infection. The rasayana had no killing
effect on the parasite in vitro. It induced significant activation of
macrophages as evidenced by increased macrophage migration index (MMI) and
phagocytic activity. Enhancement of host resistance could be one of the possible
mechanisms contributing towards the recovery of animals from the giardial
infection.

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

PMID: 7898121 [PubMed /​ indexed for MEDLINE]

56: 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]

57: Indian J Exp Biol. 1989 Nov;27(11):959/​62.

Effect of ayurvedic medicines on beta/​glucuronidase activity of Brunner's glands
during recovery from cysteamine induced duodenal ulcers in rats.

Nadar TS, Pillai MM.

Biochemical and histochemical studies revealed decreased beta/​glucuronidase
activity in the Brunner's glands of duodenal ulcerated rats. The enzyme activity
showed gradual increase during recovery. Rats treated with a mixture of
Ayurvedic medicines (Glycyrrhiza glabra, Terminalia chebula, Piper longum and
Shanka Bhasma) recovered faster with concomitant increase in beta/​glucuronidase
activity in the Brunner's glands. It can be concluded that Ayurvedic medicines
used do not act as antacid but improve the secretory status of Brunner's glands
involved in the protection against duodenal ulcer.

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

PMID: 2620935 [PubMed /​ indexed for MEDLINE]

58: J Pharm Sci. 1986 Dec;75(12):1188/​9.

Dehydropipernonaline, an amide possessing coronary vasodilating activity,
isolated from Piper longum L.

Shoji N, Umeyama A, Saito N, Takemoto T, Kajiwara A, Ohizumi Y.

An amide (dehydropipernonaline) that has coronary vasorelaxant activity was
isolated from the fruit of Piper longum L. This substance was characterized on
the basis of spectroscopic data.

Publication Types:
In Vitro

PMID: 3559927 [PubMed /​ indexed for MEDLINE]

59: Zhong Yao Tong Bao. 1983 May;8(3):5/​7.

[Introduction and propagation of Piper longum]

[Article in Chinese]

Zuo CQ.

PMID: 6224583 [PubMed /​ indexed for MEDLINE]

60: J Ethnopharmacol. 1981 Sep;4(2):229/​32.

Scientific evidence on the role of Ayurvedic herbals on bioavailability of
drugs.

Atal CK, Zutshi U, Rao PG.

Experiments were conducted to evaluate the scientific basis of the use of the
trikatu group of acrids (long pepper, black pepper and ginger) in the large
number of prescriptions in Ayurveda. [3H] vasicine and [3H] sparteine were taken
as test drugs. Piper longum (long pepper) increased the blood levels of vasicine
by nearly 233%. Under the influence of piperine, the active principle of Piper
species, sparteine blood levels increased more than 100%. The results suggest
that these acrids have the capacity to increase the bioavailability of certain
drugs. It appears that the trikatu group of drugs increase bioavailability
either by promoting rapid absorption from the gastrointestinal tract, or by
protecting the drug from being metabolised/oxidised in its first passage through
the liver after being absorbed, or by a combination of these two mechanisms.

PMID: 7311598 [PubMed /​ indexed for MEDLINE]

61: Indian J Exp Biol. 1979 Mar;17(3):289/​90.

Antifertility effects of the fruits of Piper longum in female rats.

Kholkute SD, Kekare MB, Munshi SR.

PMID: 468331 [PubMed /​ indexed for MEDLINE]

62: Planta Med. 1977 Feb;31(1):73/​5.

Antifertility activity of three indigenous plant preparations.

Munshi SR, Shetye TA, Nair RK.

PIP: The antifertility effects of preparations of Lajjal (a blend of Piper
longum, Arsenii Trisulphidium, Jawari Mastaki, and borax), Avrodhak (Lawsonia
inermis), and Kalyani (Abrus precatorius) were studied in pregnant rate.
Avrodhak, in a daily dose of either 3, 30, or 300 mg, showed a 40/​60%
inhibition of pregnancy. The other preparations were without effect. The
infertility produced by the powdered leaves of Lawsonia inermis appeared to be
permanent.

PMID: 840932 [PubMed /​ indexed for MEDLINE]

63: Tetrahedron. 1967 Apr;23(4):1769/​81.

Alkaloids of Piper longum Linn. I. Structure and synthesis of piperlongumine and
piperlonguminine.

Chatterjee A, Dutta CP.

PMID: 6047519 [PubMed /​ indexed for MEDLINE]