Polymers in Medicine

Polim. Med.
Index Copernicus (ICV 2021) – 120.65
MNiSW – 70
Average rejection rate – 27.13%
ISSN 0370-0747 (print)
ISSN 2451-2699 (online) 
Periodicity – biannual

Download original text (EN)

Polymers in Medicine

2022, vol. 52, nr 1, January-June, p. 31–36

doi: 10.17219/pim/145512

Publication type: review

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Cite as:

Imran M, Samal M, Qadir A, Ali A, Mir SR. A critical review on the extraction and pharmacotherapeutic activity of piperine. Polim Med. 2022;52(1):31–36. doi:10.17219/pim/145512

A critical review on the extraction and pharmacotherapeutic activity of piperine

Mohd Imran1,D, Monalisha Samal1,A, Abdul Qadir2,F, Asad Ali3,E, Showkat R. Mir1,F

1 Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, New Delhi, India

2 Herbalfarm Healthcare Pvt. Ltd., New Delhi, India

3 Department of Pharmaceutics, School of Pharmaceutical Education & Research, New Delhi, India


Black pepper (Piper nigrum L.) is a climbing perennial plant in the Piperaceae family. Pepper has been known since antiquity for its use both as a medicine and a spice. It is particularly valued for its pungency attributed to its principal constituent – piperine. This review summarizes the information on the biological source of piperine, its extraction and isolation strategies, physicochemical properties, and pharmacological activity – analgesic, immunomodulatory, anti-depressive, anti-diarrheal, hepatoprotective, etc. The effect of piperine on biotransformation of co-administered drugs is also presented in this review, along with the mechanisms involved in its bioavailability-enhancing effect. Its important medicinal uses, including anti-hepatotoxic, anti-diarrheal, anti-depressive, analgesic, and immunomodulatory effects, besides many other traditional uses, are compiled. Based on an exhaustive review of literature, it may be concluded that piperine is a very promising alkaloid found in members of the Piperaceae family.

Key words: piperine, pepper, extraction, Piper nigrum, bioavailability enhancement


Since antiquity, plants have been used as a source of food, spices and medicines. Among all spices, pepper has been widely discussed and named accurately “the king of spices”, due to its characteristic pungency and flavor. Therefore, it is used as an important ingredient in food worldwide. The aroma of pepper is due to the presence of volatile oil, the content of which varies from 0.5% to 7%. Pepper is particularly valued for its pungency attributed to its principal alkaloidal constituent – piperine, the content of which varies among the members of the Piperaceae family. The highest content of piperine has been reported in black pepper (Piper nigrum L.; 9%), while moderate levels have been found in long pepper (P. longum L.; 4%) and Balinese pepper (Piper retrofractum Vahl; 4.5%).1

Black pepper (P. nigrum L.) is a flowering woody perennial vine, which grows up to a maximum height of 4 m. It is native to southwestern India. It reached Egypt by 1200 BC and was extensively used by Greeks and Romans. Nowadays, major producers of black pepper include Vietnam, India, Indonesia, Malaysia, Sri Lanka, Brazil, and Costa Rica. Roots of this plant grow from the leaf nodes once vine touches the soil and its leaves are heart-shaped. Pepper fruits are small (approx. 3–4 mm in diameter) and are also known as drupes. Ripe fruits are dark brown to greyish. The plant starts bearing fruits from 4th or 5th year, and continues to bear fruits up till 7 years. Fruits are sessile, globular to subglobular in shape and have a strongly reticulated surface. They have an aromatic odor and are pungent in taste. The fruits are single-seeded. Each stem bears 20–30 spikes of fruits. Black and white pepper is made by sun-drying unripe green fruits and stony seeds, respectively. Traditional these are used as aromatics, stomachics and stimulants.1

Piper longum L., a plant native in South Asia, is a small shrub comprised of woody roots and various creeping, jointed stems, thickened at the nodes, commonly known as long pepper or Javanese, Indian or Indonesian long pepper. It is cultivated in the Assam, Tamil Nadu and Andhra Pradesh states of India and also grows wild in Malaysia, Singapore, Bhutan, and Myanmar. It is known and cultivated mainly for its fruits which are usually dried and used as a spice and seasoning. Long pepper is known to have a close relation with P. nigrum and comes in varieties such as black, green and white pepper. The fruits have characteristic aromatic, stimulant and carminative properties, and are used in the treatment of constipation, gonorrhea, diarrhea, cholera, chronic malaria, tongue paralysis, and viral hepatitis.2 Piper longum is most commonly ingested to inhibit various respiratory infections such as bronchitis cough, tumors, asthma, and some diseases of the spleen. It is well known to reduce muscular pains and inflammation, and to provide a soothing effect when applied topically. The fruit and root of the plant are widely employed in Ayurvedic system of medicine for the prevention, treatment and mitigation of various ailments. It is known as rejuvenator in Ayurveda, as it helps to enhance the appetite and dispel gas from the intestines. An infusion of P. longum root is used in promoting expulsion of the placenta after birth. It is used as sedative in insomnia and epilepsy, and as cholagogue in obstruction of bile duct and gallbladder.3 It is incorporated in essential Ayurvedic formulations such as Trikatu (composed of 3 pungent herbs, namely long pepper, black pepper and ginger). Reported research studies revealed that the consumption of Trikatu resulted in synergistic drug–drug interaction and enhanced bioavailability of the substances administered along with this formulation.4, 5

Chemistry of piperine

Piperine is the most abundant pungent alkaloid obtained from the fruits of P. nigrum L. and other peppers. It was first isolated by Hans Christian Ørsted in 1819 as yellow crystalline substance. Its structure was determined later. Its chemical formula is C17H19NO3 and its IUPAC name is 1-[5-(1, 3-benzodioxol-5-yl)-1-oxo-2, 4-pentadienyl] piperidine. It is slightly soluble in water and has the melting point of 128–130°C. It has 3 other geometric isomers, namely iso-piperine, chavicine and iso-chavicine, but all these lack pungency. Piperine has good pungent taste but on hydrolysis it gets converted to piperidine and piperic acid, due to which it loses its pungent nature. Piperine accounts for about 98% of the total alkaloids in peppers.6, 7

Other alkaloids reported in peppers containing characteristic pungency include piperanine, piperylin A, piperolein B, piperettine, and pipericine. However, these alkaloids make a small contribution to the total pungency of pepper. From the analysis of data obtained from gas chromatography-mass spectrometry (GC-MS) along with distillation–extraction of P. nigrum, it was concluded that vinylic volatile compounds are the predominant compounds present in pepper that are found in both white and black pepper.8 Jagella and Grosch concluded that compounds like α-pinene, β-pinene, limonene, α-phellandrene, myrcene, 2- and 3-methylbutanal, butyric acid, linalool, methyl propanol, and 3-methylbutyric acid are the predominant odorants present in P. nigrum.9 Figure 1 presents the chemical structure of piperine.

Extraction of piperine

Piperine is responsible for the pungency of many peppers such as black, white and long pepper. It is obtained essentially from the fruits of P. nigrum or P. longum, using various solvent extraction methods such as soaking, maceration and Soxhlet extraction. A wide range of solvents used for piperine extraction includes dichloromethane, petroleum ether, diethyl ether, alcoholic solvents like ethanol, hydrotropic solutions, and ionic-based solutions. Along with conventional extraction methods, the modern extraction techniques incorporated for piperine are supercritical carbon dioxide extraction, ultrasound-assisted extraction, pressurized liquid extraction, and microwave-assisted extraction. The dried fruits are pulverized and accurately weighed powder is used for extraction of piperine with dichloromethane at room temperature, with occasional stirring for 12 h, followed by filtration, vacuum concentration and then residue purification on an alumina column. Purified piperine can also be obtained by the crystallization from hydroalcoholic solutions and the treatment with aqueous alkali solutions.10 However, lesser amounts of piperine are attained from the crude residue by the aforementioned extraction with alcohol, filtration and then successive crystallization. Piperine can also be synthesized by the interaction of piperyl chloride (assembled from piperic acid and phosphorus pentachloride) and piperidine.

Medicinal use

Hepatoprotective activity

Piperine, when tested for treating acetaminophen-induced hepatotoxicity in mice, was found to decrease the levels of serums such as serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in a dose-dependent manner.11 The hepatoprotective activity of the methanolic extract of P. nigrum was determined in treatment of ethanol-CCl4-induced hepatic damage in Wistar rats.12 The results of other study, concerning D-glucosamine-induced hepatotoxicity in mice, indicated that piperine possess a vast therapeutic potential in the treatment of liver disorders.13

Anti-diarrheal activity

In another study, aqueous extract of black pepper was prepared in doses of 75 mg/kg, 150 mg/kg and 300 mg/kg for testing. Then, it was evaluated for its anti-motility, anti-secretary and anti-diarrheal activity in mice. Diarrhea was induced for the evaluation of anti-diarrheal activity and gastrointestinal motility by employing castor oil and magnesium sulfate in mice. The anti-motility and anti-secretary activities of P. nigrum were attributed to the presence of alkaloids, mainly piperine.14

Antidepressant activity

The corticosterone-induced model of depression in mice was used to study the effects of piperine as antidepressant and its possible mechanism of action. In this study, corticosterone injections were given to mice for 3 weeks to induce depression, and the mice were observed for the decreased brain-derived neurotrophic factor protein and mRNA levels in the hippocampus. These changes disappeared after the mice had been treated with piperine. These results demonstrated that piperine has potential anti-depressive activity in the corticosterone-induced depression model in mice.15 Piperine also showed anti-depressive-like effects in mice with chronic mild stress.16

Immunomodulatory activity

Piperine was evaluated for its immunomodulatory and antitumor activities. It was found to be cytotoxic to Ehrlich ascites carcinoma (EAC) cells, known widely as Ehrlich cells and Dalton’s lymphoma ascites. Increased white blood cells (WBC), bone marrow cells and alpha esterase-positive cells count was observed in mice after treatment with piperine.17

Analgesic activity

In vivo evaluation of piperine was performed to determine the analgesic effects in acetic-acid induced writhing and tail flick assay models in mice. The acetic-acid induced writhing model showed a significant reduction after intraperitoneal administration of piperine in mice at dose of 30 mg/kg, 50 mg/kg and 70 mg/kg. Piperine showed greater inhibition when compared with indomethacin at a dose of 30 mg/kg administered intraperitoneally (ip.). In the tail flick assay, an ip. injection of piperine and morphine at doses of 30 mg/kg and 5 mg/kg, respectively, resulted in remarkable increase in reaction time.18

Anti-tubercular activity

In vitro evaluation of piperine was determined in a murine model of Mycobacterium tuberculosis infection. The results showed an increase in the secretion of Th1 cytokines (interferon gamma (IFN-γ) and interleukin 2 (IL-2)) and in macrophage activation.19

Effect of piperine on metabolism

Piperine regulates the metabolic pathway of many components inside the body and is also involved in altering the bioavailability of many therapeutically crucial drugs and nutrients. Through various mechanisms, it stimulates the absorption of drugs and other nutrients from the gastrointestinal tract. It works by changing the membrane dynamics, thus enhancing the permeability at the site of drug absorption. It is also responsible for extending the serum half-life of substances such as β-carotene and coenzyme Q10, and declining the metabolism of many drugs by handicapping metabolizing enzymes like cytochrome BS, uridine 5’-diphospho (UDP)-glucuronyltransferase, UDP-glucose dehydrogenase (UDP-GDH), CYP3A4, aryl hydrocarbon hydroxylase, and nicotinamide adenine dinucleotide phosphate (NADPH) cytochrome.20 Piperine has been reported to influence the bioavailability of many drugs such as amoxicillin, acefotaxime, norfloxacin,21 metronidazole, carbamazepine,22 oxytetracycline, pentobarbitone, phenytoin,23 resveratrol,24 β-carotene,25 curcumin, tiferron, nevirapine, docetaxel,26 theophylline, and propranolol.27 Hence, piperine is also known as bioavailability enhancer. The other uses of piperine are summarized in Table 1.

Antibacterial activity

Piperine and black pepper oil are powerful antibacterial agents – especially piperine, which is active against both Gram-positive and Gram-negative microorganisms.64

Appetite suppressant

The findings indicated that preloading with BPB (black pepper-based beverage) reduced hunger, desire to eat and prospective intake, while increasing satiety and a feeling of fullness. Thus, this demonstrates appetite suppressing action of piperine.65

Piperine enhances body efficiency

Piperine is an alkaloid present in black pepper (P. nigrum), long pepper (P. longum) and other species belonging to the Piperaceae family. It is responsible for the black pepper distinct biting quality. Piperine has many pharmacological effects, especially against chronic diseases, such as reducing insulin-resistance and anti-inflammatory effects, and mitigating hepatic steatosis.

Side effects

Major side effects of piperine include loss of potassium, acid reflux, constipation, and nausea. Pepper can cause allergic reactions like sneezing, hives, rashes, and swelling of the tongue and mouth, and even profound respiratory reactions in cases of severe allergic reactions.

Isolation of piperine

Several methods have been developed for the isolation of piperine from black pepper, namely Soxhlet extraction, hydrotropic extraction, supercritical fluid extraction, ionic liquid-based extraction, and microwave-assisted extraction. However, in one study, bulk isolation of piperine from black pepper and white pepper fruits was performed using Soxhlet extraction with 95% ethanol, and from the concentrated extracts, the yellow-colored needles were obtained, which were isolated by precipitation with 10% alcoholic potassium hydroxide (KOH) solution. It was then followed by purification by recrystallizing the obtained crystals with dichloromethane followed by few drops of n-Hexane that will lead to the formation of rod-like, pale yellow crystals of piperine.66


Based on an exhaustive review of literature, it may be concluded that piperine is a very promising alkaloid found in members of Piperaceae family. This review aimed to gather information about the biological source of piperine, its extraction and isolation strategies, physicochemical properties, and pharmacological activity. The effect of piperine on biotransformation of co-administered drugs is also presented in this review. The major mechanisms involved in its bioavailability-enhancing activity are: a) acting on drug metabolizing enzyme; b) disrupting the supply of blood to gastrointestinal tract and the membrane fluidity; c) affecting drug transport; and d) disturbing drug absorption.


Table 1. Uses of piperine and health benefits




Traditional uses

flavor, cough, diuretic, antispasmodic, increases saliva flow, antiseptic, dyspepsia, central nervous system (CNS) stimulant, digestive tonic, aroma, flatulence, indigestion, strep throat, germicide, blood purifier, bactericide, analgesic, antitoxic, religious ceremony, aphrodisiac, pain, antipyretic, insecticide, rheumatism, diabetes, muscle aches

3, 9, 28, 29, 30, 31, 32, 33, 34

Modern uses







increased hypersensitivity response


cognitive improvement

39, 40




42, 43

reduce high fat induce oxidative stress

44, 45





lipid metabolism acceleration


increased food absorption rate

49, 50, 51


52, 53


54, 55

synergic nociceptive effect




hepatoprotective activity


increased bile secretion

59, 60

drug metabolism


hepatic enzyme activity


inhibit lung metastatic



Fig. 1. Chemical structure of piperine

References (66)

  1. The Wealth of India. A Dictionary of Indian Raw Materials and Industrial Products. First Supplementary Series: Raw Materials. New Delhi, India: Publi-cations and Information Directorate (PID); 2003:318–319.
  2. Satyavati GV, Gupta AK, Tandon N, eds. Medicinal Plants of India. New Delhi, India: Indian Council of Medical Research (ICMR); 1987:426–456.
  3. Pei YQ. A review of pharmacology and clinical use of piperine and its derivatives and uses. Epilepsia. 1983;24(2):177–181. doi:10.1111/j.1528-1157.1983.tb04877.x
  4. Handbook of Domestic Medicine and Common Ayurvedic Remedies. New Delhi, India: Central Council for Research in Indian Medicine and Home-opathy; 1979:91–112.
  5. Antarkar DS, Vaidya AB. Therapeutic approach to malaria in Ayurveda. In: Subrahmanyam D, Radhakrishna V, eds. Symposium on Recent Advances in Protozoan Diseases. Bombay, India: Hindustan Ciba-Geigy Research Centre Goregaon; 1983:96–101.
  6. Hirasa K, Takemasa M. Spice Science and Technology. Boca Raton, USA: CRC Press; 1998:98–107.
  7. Parmar VS, Jain SC, Bisht KS, Jain R, Taneja P, Jha A. Phytochemistry of the genus Piper. Phytochemistry. 1997;46(4):597–673. doi:10.1016/S0031-9422(97)00328-2
  8. Chen W, Dou H, Ge C. Comparison of volatile compounds in pepper (P. nigrum L.) by simultaneous distillation extraction (SDE) and GC-MS. Adv Mater Res. 2011;236–238:2643–2646. doi:10.4028/www.scientific.net/AMR.236-238.2643
  9. Jagella T, Grosch W. Flavour and off-flavour compounds of black and white pepper (Piper nigrum L.). II. Odour activity values of desirable and undesirable odorants of black pepper. Eur Food Res Technol. 1999;209:22–26. doi:10.1007/s002170050450
  10. Gorgani L, Mohammadi M, Najafpour GD, Nikzad M. Piperine, the bioactive compound of black pepper: From isolation to medicinal formulations. Compr Rev Food Sci Food Saf. 2017;16(1):124–140. doi:10.1111/1541-4337.12246
  11. Sabina EP, Souriyan ADH, Jackline D, Rasool MK. Piperine, an active ingredient of black pepper attenuates acetaminophen-induced hepatotoxicity in mice. Asian Pac Trop Dis. 2010;3(12):971–976. doi:10.1016/S1995-7645(11)60011-4
  12. Nirwane AM, Bapat AR. Effect of methanolic extract of Piper nigrum fruits in ethanol-CCl4-induced hepatotoxicity in Wistar rats. Der Pharmacia Letter. 2012;4:795–802.
  13. Matsuda H, Ninomiya K, Morikawa T, Yasuda D, Yamaguchi I. Protective effects of amide constituents from the fruit of Piper chaba on D-galactosamine/TNF-alpha-induced cell death in mouse hepatocytes. Bioorg Med Chem Lett. 2008;18(6):2038–2042. doi:10.1016/j.bmcl.2008.01.101
  14. Shamkuwar PB, Shahi SR, Jadhav ST. Evaluation of anti-diarrheal effect of black pepper (Piper nigrum L). Asian J Plant Sci Res. 2012;2:48–53. https://naturalingredient.org/wp/wp-content/uploads/AJPSR-2012-2-1-48-53.pdf
  15. Mao QQ, Huang Z, Zhong XM, Xian YF, Ip SP. Piperine reverses the effects of corticosterone on behavior and hippocampal BDNF expression in mice. Neurochem Int. 2014;74:36–41. doi:10.1016/j.neuint.2014.04.017
  16. Li S, Wang C, Wang M, Li W, Matsumoto K. Antidepressant like effects of piperine in chronic mild stress treated mice and its possible mechanisms. Life Sci. 2007;80(15):1373–1381. doi:10.1016/j.lfs.2006.12.027
  17. Sunila ES, Kuttan G. Immunomodulatory and antitumor activity of Piper longum Linn. and piperine. J Ethnopharmacol. 2004;90(2–3):339–346. doi:10.1016/j.jep.2003.10.016
  18. Bukhari IA, Pivac N, Alhumayyd MS, Mahesar AL, Gilani AH. The analgesic and anticonvulsant effects of piperine in mice. J Physiol Pharmacol. 2013;64(6):789–794. PMID:24388894
  19. Sharma S, Kalia NP, Suden P, Chauhan PS, Kumar M. Protective efficacy of piperine against Mycobacterium tuberculosis. Tuberculosis (Edinb). 2014;94(4):389–396. doi:10.1016/j.tube.2014.04.007
  20. Badmaev V, Majeed M, Prakash L. Piperine derived from black pepper increases plasma levels of coenzyme Q10 following oral supplementation. J Nutr Biochem. 2000;11(2):109–113. doi:10.1016/s0955-2863(99)00074-1
  21. Hiwale AR. Effect of coadministration of piperine on pharmacokinetics of b-lactam antibiotics in rats. Indian J Exp Biol. 2002;40(3):277–281. PMID:12635696
  22. Pattanaik S, Hota D, Prabhakar S. Pharmacokinetic interaction of single dose of piperine with steady state carbamazepine in epilepsy patient. Phytother Res. 2009;23(9):1281–1286. doi:10.1002/ptr.2676
  23. Pattanaik S, Hota D, Prabhakar S. Effect of piperine on the steady-state pharmacokinetics of phenytoin in patients with epilepsy. Phytother Res. 2006;20(8):683–686. doi:10.1002/ptr.1937
  24. Johnson JJ, Nihal M, Siddiqui IA, Scarlett CO, Bailey HH. Enhancing the bioavailability of resveratrol by combining it with piperine. Mol Nutr Food Res. 2011;55(8):1169–1176. doi:10.1002/mnfr.201100117
  25. Badmaev V, Majeed M, Norkus EP. Piperine, an alkaloid derived from black pepper increases serum response of β-carotene during 14 days of oral b-carotene supplementation. Nutr Res. 1999;19(3):381–388. doi:10.1016/S0271-5317(99)00007-X
  26. Makhov P, Golovine K, Canter D, Kutikov A, Simhan J. Co-administration of piperine and docetaxel results in improved anti-tumor efficacy via inhibition of CYP3A4 activity. Prostate. 2012;72(6):661–667. doi:10.1002/pros.21469
  27. Bano G, Raina RK, Zutshi U. Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers. Eur J Clin Pharmacol. 1991;41(6):615–617. doi:10.1007/BF00314996
  28. Ahmad N, Fazal H, Abbasi BH, Farooq S, Ali M. Biological role of Piper nigrum L. (black pepper): A review. Asian Pac J Trop Biomed. 2012;2(3 Suppl):S1945–S1953. doi:10.1016/S2221-1691(12)60524-3
  29. Db M, Sreedharan S, Mahadik KR. Role of piperine as an effective bioenhancer in drug absorption. Pharm Anal Acta. 2018;9(7):1–4. doi:10.4172/2153-2435.1000591
  30. Srinivasan K. Black pepper and its pungent principle-piperine: A review of diverse physiological effects. Crit Rev Food Sci Nutr. 2007;47(8):735–748. doi:10.1080/10408390601062054
  31. Capasso R, Izzo AA, Borrelli F. Effect of piperine, the active ingredient of black pepper on intestinal secretion in mice. Life Sci. 2002;71(19):2311–2317. doi:10.1016/s0024-3205(02)02019-2
  32. Myers BM, Smith JL, Graham DY. Effect of red pepper and black pepper on the stomach. Am J Gastroenterol. 1987;82(3):211–214. PMID:3103424
  33. Khan M, Siddiqui M. Antimicrobial activity of Piper fruits. Natural Product Radiance. 2007;6(2):111–113. http://nopr.niscair.res.in/bitstream/123456789/7845/1/NPR%206%282%29%20111-113.pdf
  34. Doucette CD, Hilchie AL, Liwski R, Hoskin DW. Piperine, a dietary phytochemical, inhibits angiogenesis. J Nutr Biochem. 2013;24(1):231–239. doi:10.1016/j.jnutbio.2012.05.009
  35. Atal CK, Dubey RK, Singh J. Biochemical basis of enhanced drug bioavailability of piperine: Evidence that piperine is a potent inhibitor of drug metabolism. J Pharmacol Exp Ther. 1985;232(1):258–262. PMID:3917507
  36. Taqvi SI, Shah AJ, Gilani AH. Blood pressure lowering and vasomodulator effects of piperine. J Cardiovasc Pharmacol. 2008;52(5):452–458. doi:10.1097/FJC.0b013e31818d07c0
  37. Agbor GA, Akinfiesoye L, Sortino J, Johnson R, Vinson JA. Piper species protect cardiac, hepatic and renal antioxidant status of atherogenic diet fed hamsters. Food Chem. 2012;134(3):1354–1359. doi:10.1016/j.foodchem.2012.03.030
  38. Dogra RKS, Khanna S, Shanker R. Immunotoxicological effects of piperine in mice. Toxicology. 2004;196(3):229–236. doi:10.1016/j.tox.2003.10.006
  39. Hritcu L, Noumedem JA, Cioanca O, Hancianu M, Kuete V. Methanolic extract of Piper nigrum fruits improves memory impairment by decreasing brain oxidative stress in amyloid beta(1-42) rat model of Alzheimer’s disease. Cell Mol Neurobiol. 2014;34(3):437–449. doi:10.1007/s10571-014-0028-y
  40. Chonpathompikunlert P, Wattanathorn J, Muchimapura S. Piperine, the main alkaloid of Thai black pepper, protects against neurodegeneration and cognitive impairment in animal model of cognitive deficit like condition of Alzheimer’s disease. Food Chem Toxicol. 2010;48(3):798–802. doi:10.1016/j.fct.2009.12.009
  41. Kaushik D, Rani R, Kaushik P, Sacher D, Yadav J. In vivo and in vitro antiasthmatic studies of plant Piper longum Linn. Int J Pharmacol. 2012;8(3):192–197. doi:10.3923/ijp.2012.192.197
  42. Khajuria A, Thusu N, Zutshi U, Bedi KL. Piperine modulation of carcinogen induced oxidative stress in intestinal mucosa. Mol Cell Biochem. 1998;189(1–2):113–118. doi:10.1023/a:1006877614411
  43. Mittal R, Gupta RL. In vitro antioxidant activity of piperine. Exp Clin Psychopharmacol. 2000;22(5):271–274. doi:10.1358/mf.2000.22.5.796644
  44. Vijayakumar RS, Surya D, Nalini N. Antioxidant efficacy of black pepper (Piper nigrum L.) and piperine in rats with high fat diet induced oxidative stress. Redox Rep. 2004;9(2):105–110. doi:10.1179/135100004225004742
  45. Naidu KA, Thippeswamy NB. Inhibition of human low density lipoprotein oxidation by active principles from spices. Mol Cell Biochem. 2002;229(1–2):19–23. doi:10.1023/a:1017930708099
  46. Chen CY, Li W, Qu KP, Chen CR. Piperine exerts anti-seizure effects via the TRPV1 receptor in mice. Eur J Pharmacol. 2013;714(1–3):288–294. doi:10.1016/j.ejphar.2013.07.041
  47. Lakshmi V, Kumar R, Agarwal SK, Dhar JD. Antifertility activity of Piper longum L. in female rats. Nat Prod Res. 2006;20(3):235–239. doi:10.1080/14786410500045465
  48. Duangjai A, Ingkaninan K, Praputbut S, Limpeanchob N. Black pepper and piperine reduce cholesterol uptake and enhance translocation of cholesterol transporter proteins. J Nat Med. 2013;67(2):303–310. doi:10.1007/s11418-012-0682-7
  49. Platel K, Srinivasan K. Influence of dietary spices or their active principles on digestive enzymes of small intestinal mucosa in rats. Int J Food Sci Nutr. 1996;47(1):55–59. doi:10.3109/09637489609028561
  50. Platel K, Srinivasan K. Influence of dietary spices and their active principles on pancreatic digestive enzymes in albino rats. Nahrung. 2000;44(1):42–46. doi:10.1002/(SICI)1521-3803(20000101)44:1<42::AID-FOOD42>3.0.CO;2-D
  51. Platel K, Srinivasan K. Studies on the influence of dietary spices on food transit time in experimental rats. Nutr Res. 2001;21(9):1309–1314. doi:10.1016/S0271-5317(01)00331-1
  52. Mujumdar AM, Dhuley JN, Deshmukh VK. Anti-inflammatory activity of piperine. Jap J Med Sci Biol. 1990;43(3):95–100. doi:10.7883/yoken1952.43.95
  53. Bang JS, Oh da H, Choi HM, Sur BJ, Lim SJ. Anti-inflammatory and anti-arthritic effects of piperine in human interleukin 1beta-stimulated fibro-blast-like synoviocytes and in rat arthritis models. Arthritis Res Ther. 2009;11(2):R49. doi:10.1186/ar2662
  54. Samykutty A, Shetty AV, Dakshinamoorthy G, Bartik MM, Johnson GL, Webb B. Piperine, a bioactive component of pepper spice, exerts therapeutic effects on androgen dependent and androgen independent prostate cancer cells. PLoS One. 2013;8(6):e65889. doi:10.1371/journal.pone.0065889
  55. Manoharan S, Balakrishnan S, Menon V, Alias L, Reena A. Chemopreventive efficacy of curcumin and piperine during 7,12-dimethylbenz[a] anthracene-induced hamster buccal pouch carcinogenesis. Singapore Med J. 2009;50(2):139–146. PMID:19296028
  56. Gupta SK, Velpandian T, Sengupta S. Influence of piperine on nimesulide induced antinociception. Phytother Res. 1998;12(4):266–269. doi:10.1002/(SICI)1099-1573(199806)12:4<266::AID-PTR291>3.0.CO;2-S
  57. Bai YF, Xu H. Protective action of piperine against experimental gastric ulcer. Acta Pharmacol Sin. 2000;21(4):357–359. PMID:11324467
  58. Piyachaturawat P, Kingkaeohoi S, Toskulkao C. Potentiation of carbon tetrachloride hepatotoxicity by piperine. Drug Chem Toxicol. 1995;18(4):333–344. doi:10.3109/01480549509014327
  59. Bhat GB, Chandrasekhara N. Effect of black pepper and piperine on bile secretion and composition in rats. Nahrung. 1987;31(9):913–916. doi:10.1002/food.19870310916
  60. Ononiwu IM, Ibeneme CE, Ebong OO. Effects of piperine on gastric acid secretion in albino rats. Afr J Med Sci. 2002;31(4):293–295. PMID:15027765
  61. Dalvi RR, Dalvi PS. Differences in the effects of piperine and piperonylbutoxide on hepatic drug-metabolizing enzyme system in rats. Drug Chem Toxicol. 1991a;14(1–2):219–229. doi:10.3109/01480549109017878
  62. Dalvi RR, Dalvi PS. Comparison of the effects of piperine administered intragastrically and intraperitoneally on the liver and liver mixed function oxidases in rats. Drug Metabol Drug Interaction. 1991b;9(1):23–30. doi:10.1515/dmdi.1991.9.1.23
  63. Selvendiran K, Sakthisekaran D. Chemopreventive effect of piperine on modulating lipid peroxidation and membrane bound enzymes in benzo(a) pyrene induced lung carcinogenesis. Biomed Pharmacother. 2004;58(4):264–267. doi:10.1016/j.biopha.2003.08.027
  64. Hikal DM. Antibacterial activity of piperine and black pepper oil. Biosci Biotechnol Res Asia. 2018;15(4):877–880. doi:10.13005/bbra/2697
  65. Zanzer YC, Plaza M, Dougkas A, Turner C, Östman E. Black pepper-based beverage induced appetite-suppressing effects without altering post-prandial glycaemia, gut and thyroid hormones or gastrointestinal well-being: A randomized crossover study in healthy subjects. Food Function. 2018;9(5):2774–2786. doi:10.1039/c7fo01715d
  66. Khan ZR, Moni F, Sharmin S, et al. Isolation of bulk amount of piperine as active pharmaceutical ingredient (API) from black pepper and white pepper (Piper nigrum L.). Pharmacol Pharm. 2017;8(7):253–262. doi:10.4236/pp.2017.87018