Piperine: Old Spice and New Nutraceutical?

Author(s): Katarina Smilkov*, Darinka G. Ackova, Aleksandar Cvetkovski, Tatjana Ruskovska, Bojana Vidovic, Mustafa Atalay.

Journal Name: Current Pharmaceutical Design

Volume 25 , Issue 15 , 2019


Background: Many of the activities associated with pepper fruits have been attributed to piperine, the most active compound present in these spices.

Objective: This paper aims to provide an overview of the known properties of piperine, i.e. piperine’s chemistry, its physiological activity, documented interactions as a bioenhancer and reported data concerning its toxicity, antioxidant properties and anticancer activity.

Discussion: It is known that piperine possesses several properties. In its interaction with other drugs, it can act as a bioavailability enhancer; this effect is also manifested in combination with other nutraceuticals, e.g. with curcumin, i.e. piperine can modify curcumin’s antioxidant, anti-inflammatory, antimicrobial and anticancer effects. Piperine displays significant immunomodulating, antioxidant, chemopreventive and anticancer activity; these effects have been shown to be dose-dependent and tissue-specific. However, the main limitation associated with piperine seems to be its low bioavailability, a disadvantage that innovative formulations are overcoming.

Conclusion: It is predicted that an increasing number of studies will focus on piperine, especially those directed towards unraveling its properties at molecular level. The current knowledge about the action of piperine will form a foundation for ways to improve piperine’s bioavailability e.g. exploitation of different carrier systems. The therapeutical applications of this compound will be clarified, and piperine will be recognized as an important nutraceutical.

Keywords: Piperine, nutraceutical, characteristics, interactions, enhancer, antioxidant, anticancer.

Wildman REC, Kelley M. Nutraceuticals and Functional Foods.Handbook of Nutraceuticals and Functional Foods 2nd ed. 2007; pp. 1-21.
Santini A, Tenore GC, Novellino E. Nutraceuticals: A paradigm of proactive medicine. Eur J Pharm Sci 2017; 96: 53-61. [http://dx.doi.org/10.1016/j.ejps.2016.09.003]. [PMID: 27613382].
Sharma M, Pankaj D, Ajay R, Anil D. Nutrition nutraceuticals: A proactive approach for health care.Nutraceuticals. Nanotechnology in the Food Industry 2006; Vol. 4: 79-116.
Arai S. Studies on functional foods in Japan--state of the art. Biosci Biotechnol Biochem 1996; 60(1): 9-15. [http://dx.doi.org/10.1271/bbb.60.9]. [PMID: 8824819].
Diplock AT, Aggett PJ, Ashwell M, Bornet F, Fern EB, Roberfroid MB. Scientific concepts of functional foods in Europe. Consensus document. Br J Nutr 1999; 81(Suppl. 1): S1-S27. [http://dx.doi.org/10.1017/S0007114599000471]. [PMID: 10999022].
Koch A, Brandenburger S, Türpe S, Birringer M. The need for a legal distinction of nutraceuticals. Food Nutr Sci 2014; 5: 905-13. [http://dx.doi.org/10.4236/fns.2014.510100].
Brower V. Nutraceuticals: Poised for a healthy slice of the healthcare market? Nat Biotechnol 1998; 16(8): 728-31. [http://dx.doi.org/10.1038/nbt0898-728]. [PMID: 9702769].
Aronson JK. Defining ‘nutraceuticals’: Neither nutritious nor pharmaceutical. Br J Clin Pharmacol 2017; 83(1): 8-19. [http://dx.doi.org/10.1111/bcp.12935]. [PMID: 26991455].
Sharif MK, Khalid R. Nutraceuticals: Myths Versus Realities. In: Holban AM Grumezescu AM, Eds Therapeutic Foods . 2018; pp. 3-21.
Zeisel SH. Regulation of “nutraceuticals”. Science 1999; 285(5435): 1853-5. [http://dx.doi.org/10.1126/science.285.5435.1853]. [PMID: 10515789].
Hathcock J. Dietary supplements: How they are used and regulated. J Nutr 2001; 131(3s): 1114S-7S. [http://dx.doi.org/10.1093/jn/131.3.1114S]. [PMID: 11238828].
Nicoletti M. Nutraceuticals and botanicals: Overview and perspectives. Int J Food Sci Nutr 2012; 63(Suppl. 1): 2-6. [http://dx.doi.org/10.3109/09637486.2011.628012]. [PMID: 22360273].
Allen LV. Nutritional Products Handbook of Nonprescription Drugs . 1997.
Gupta S, Chauhan D, Mehla K, Sood P, Nair A. An overview of nutraceuticals: Current scenario. J Basic Clin Pharm 2010; 1(2): 55-62. [PMID: 24825966].
da Costa JP. A current look at nutraceuticals – Key concepts and future prospects. Trends Food Sci Technol 2017; 62: 68-78. [http://dx.doi.org/10.1016/j.tifs.2017.02.010].
McClements DJ, Li F, Xiao H. The Nutraceutical bioavailability classification scheme: Classifying nutraceuticals according to factors limiting their oral bioavailability. Annu Rev Food Sci Technol 2015; 6: 299-327. [http://dx.doi.org/10.1146/annurev-food-032814-014043]. [PMID: 25705933].
Pandey M, Verma RK, Saraf SA. Nutraceuticals: New era of medicine and health. Asian J Pharm Clin Res 2010; 3: 11-5.
Catinean A, Neag MA, Muntean DM, Bocsan IC, Buzoianu AD. An overview on the interplay between nutraceuticals and gut microbiota. PeerJ 2018; 6e4465 [http://dx.doi.org/10.7717/peerj.4465]. [PMID: 29576949].
Santini A, Cammarata SM, Capone G, et al. Nutraceuticals: Opening the debate for a regulatory framework. Br J Clin Pharmacol 2018; 84(4): 659-72. [http://dx.doi.org/10.1111/bcp.13496]. [PMID: 29433155].
Kurian A. Health benefits of herbs and spices Handbook of Herbs and Spices 2nd ed. 2012; pp. 72-88.
Hussain SA, Panjagari NR, Singh RR, Patil GR. Potential herbs and herbal nutraceuticals: Food applications and their interactions with food components. Crit Rev Food Sci Nutr 2015; 55(1): 94-122. [http://dx.doi.org/10.1080/10408398.2011.649148]. [PMID: 24915396].
Gul K, Singh AK, Jabeen R. Nutraceuticals and functional foods: The foods for the future world. Crit Rev Food Sci Nutr 2016; 56(16): 2617-27. [http://dx.doi.org/10.1080/10408398.2014.903384]. [PMID: 25629711].
Yashin A, Yashin Y, Xia X, Nemzer B. Antioxidant activity of spices and their impact on human health: A review. Antioxidants 2017; 6(3): 70. [http://dx.doi.org/10.3390/antiox6030070]. [PMID: 28914764].
Mao XY, Jin MZ, Chen JF, Zhou HH, Jin WL. Live or let die: Neuroprotective and anti-cancer effects of nutraceutical antioxidants. Pharmacol Ther 2018; 183: 137-51. [http://dx.doi.org/10.1016/j.pharmthera.2017.10.012]. [PMID: 29055715].
Adefegha SA. Functional foods and nutraceuticals as dietary intervention in chronic diseases; Novel perspectives for health promotion and disease prevention. J Diet Suppl 2018; 15(6): 977-1009. [http://dx.doi.org/10.1080/19390211.2017.1401573]. [PMID: 29281341].
Dudhatra GB, Mody SK, Awale MM, et al. A comprehensive review on pharmacotherapeutics of herbal bioenhancers. ScientificWorldJournal 2012; 2012637953 [http://dx.doi.org/10.1100/2012/637953]. [PMID: 23028251].
Ajazuddin AA, Alexander A, Qureshi A, et al. Role of herbal bioactives as a potential bioavailability enhancer for Active Pharmaceutical Ingredients. Fitoterapia 2014; 97: 1-14. [http://dx.doi.org/10.1016/j.fitote.2014.05.005]. [PMID: 24862064].
Gupta RC, Srivastava A, Lall R. Toxicity potential of nutraceuticals. Methods Mol Biol 2018; 1800: 367-94. [http://dx.doi.org/10.1007/978-1-4939-7899-1_18]. [PMID: 29934903].
Meghwal M, Goswami TK. Piper nigrum and piperine: An update. Phytother Res 2013; 27(8): 1121-30. [http://dx.doi.org/10.1002/ptr.4972]. [PMID: 23625885].
Vijayakumar RS, Surya D, Senthilkumar R, Nalini N. Hypolipidemic effect of black pepper (Piper nigrum Linn.) in rats fed high fat diet. J Clin Biochem Nutr 2002; 32: 31-42. [http://dx.doi.org/10.3164/jcbn.32.31].
Darshan S, Doreswamy R. Patented antiinflammatory plant drug development from traditional medicine. Phytother Res 2004; 18(5): 343-57. [http://dx.doi.org/10.1002/ptr.1475]. [PMID: 15173991].
Srinivasan K. Black pepper and its pungent principle-piperine: A review of diverse physiological effects. Crit Rev Food Sci Nutr 2007; 47(8): 735-48. [http://dx.doi.org/10.1080/10408390601062054]. [PMID: 17987447].
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. [http://dx.doi.org/10.1016/j.fct.2009.12.009]. [PMID: 20034530].
Han H-K. The effects of black pepper on the intestinal absorption and hepatic metabolism of drugs. Expert Opin Drug Metab Toxicol 2011; 7(6): 721-9. [http://dx.doi.org/10.1517/17425255.2011.570332]. [PMID: 21434835].
Umar S, Golam Sarwar AH, Umar K, et al. Piperine ameliorates oxidative stress, inflammation and histological outcome in collagen induced arthritis. Cell Immunol 2013; 284(1-2): 51-9. [http://dx.doi.org/10.1016/j.cellimm.2013.07.004]. [PMID: 23921080].
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: 124-40. [http://dx.doi.org/10.1111/1541-4337.12246].
Shaikh J, Ankola DD, Beniwal V, Singh D, Kumar MN. Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer. Eur J Pharm Sci 2009; 37(3-4): 223-30. [http://dx.doi.org/10.1016/j.ejps.2009.02.019]. [PMID: 19491009].
Kesarwani K, Gupta R, Mukerjee A. Bioavailability enhancers of herbal origin: An overview. Asian Pac J Trop Biomed 2013; 3(4): 253-66. [http://dx.doi.org/10.1016/S2221-1691(13)60060-X]. [PMID: 23620848].
Okwute SK, Egharevba HO. Piperine-Type Amides: Review of the Chemical and Biological Characteristics. Int J Chem 2013; 5: 99-122. [http://dx.doi.org/10.5539/ijc.v5n3p99].
Grynpas M, Lindley FP. The crystal and molecular structure of 1-piperoylpiperidine. Acta Crystallogr B Struct Sci Cryst Eng Mater 1975; 31: 2663-7. [http://dx.doi.org/10.1107/S0567740875008412].
Kakarala M, Dubey SK, Tarnowski M, et al. Ultra-low flow liquid chromatography assay with ultraviolet (UV) detection for piperine quantitation in human plasma. J Agric Food Chem 2010; 58(11): 6594-9. [http://dx.doi.org/10.1021/jf100657r]. [PMID: 20465211].
Chavarria D, Silva T, Magalhães e Silva D, Remião F, Borges F. Lessons from black pepper: Piperine and derivatives thereof. Expert Opin Ther Pat 2016; 26(2): 245-64. [http://dx.doi.org/10.1517/13543776.2016.1118057]. [PMID: 26560940].
Vasavirama K, Upender M. Piperine: A valuable alkaloid from piper species. Int J Pharm Pharm Sci 2014; 6: 34-8.
De Mey E, De Maere H, Dewulf L, et al. Application of accelerated solvent extraction (ASE) and thin layer chromatography (TLC) to determination of piperine in commercial samples of pepper (Piper nigrum L.). J Liq Chromatogr Relat Technol 2014; 37: 2980-8. [http://dx.doi.org/10.1080/10739149.2014.907014].
Ezawa T, Inoue Y, Tunvichien S, Suzuki R, Kanamoto I. Changes in the physicochemical properties of piperine/β-cyclodextrin due to the formation of inclusion complexes. Int J Med Chem 2016; 20168723139 [PMID: 8723139].
Reen RK, Jamwal DS, Taneja SC, et al. Impairment of UDP-glucose dehydrogenase and glucuronidation activities in liver and small intestine of rat and guinea pig in vitro by piperine. Biochem Pharmacol 1993; 46(2): 229-38. [http://dx.doi.org/10.1016/0006-2952(93)90408-O]. [PMID: 8347144].
Jamwal DS, Singh J. Effects of piperine on enzyme activities and bioenergetic functions in isolated rat liver mitochondria and hepatocytes. J Biochem Toxicol 1993; 8(4): 167-74. [http://dx.doi.org/10.1002/jbt.2570080402]. [PMID: 8114060].
Koul S, Koul JL, Taneja SC, et al. Structure-activity relationship of piperine and its synthetic analogues for their inhibitory potentials of rat hepatic microsomal constitutive and inducible cytochrome P450 activities. Bioorg Med Chem 2000; 8(1): 251-68. [http://dx.doi.org/10.1016/S0968-0896(99)00273-4]. [PMID: 10968285].
Tawani A, Amanullah A, Mishra A, Kumar A. Evidences for Piperine inhibiting cancer by targeting human G-quadruplex DNA sequences. Sci Rep 2016; 6: 39239. [http://dx.doi.org/10.1038/srep39239]. [PMID: 27995955].
Bhat BG, Chandrasekhara N. Studies on the metabolism of piperine: Absorption, tissue distribution and excretion of urinary conjugates in rats. Toxicology 1986; 40(1): 83-92. [http://dx.doi.org/10.1016/0300-483X(86)90048-X]. [PMID: 3715893].
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): 113-8. [http://dx.doi.org/10.1023/A:1006877614411]. [PMID: 9879661].
Suresh DV, Mahesha HG, Rao AGA, Srinivasan K. Binding of bioactive phytochemical piperine with human serum albumin: A spectrofluorometric study. Biopolymers 2007; 86(4): 265-75. [http://dx.doi.org/10.1002/bip.20735]. [PMID: 17407131].
Wang X, Peng W, Zhang Q, et al. Pharmacokinetics of piperine capsules in healthy volunteers. Zhongnan Yaoxue 2010; 8: 513-6.
Burdock GA. Fenaroli’s handbook of flavor ingredients. 6th ed. 2010.
Scientific Opinion on Flavouring Group Evaluation 86, Revision 2 (FGE.86Rev2): Consideration of aliphatic and arylalkyl amines and amides evaluated by JECFA. EFSA J 2015; 13: 3998. [http://dx.doi.org/10.2903/j.efsa.2015.3998].
Veerareddy PR, Vobalaboina V, Nahid A. Formulation and evaluation of oil-in-water emulsions of piperine in visceral leishmaniasis. Pharmazie 2004; 59(3): 194-7. [PMID: 15074591].
Pachauri M, Gupta ED, Ghosh PC. Piperine loaded PEG-PLGA nanoparticles: Preparation, characterization, and targeted delivery for adjuvant breast cancer chemotherapy. J Drug Deliv Sci Technol 2015; 29: 269-82. [http://dx.doi.org/10.1016/j.jddst.2015.08.009].
Piyachaturawat P, Glinsukon T, Toskulkao C. Acute and subacute toxicity of piperine in mice, rats and hamsters. Toxicol Lett 1983; 16(3-4): 351-9. [http://dx.doi.org/10.1016/0378-4274(83)90198-4]. [PMID: 6857729].
Karekar VR, Mujumdar AM, Joshi SS, Dhuley J, Shinde SL, Ghaskadbi S. Assessment of genotoxic effect of piperine using Salmonella typhimurium and somatic and somatic and germ cells of Swiss albino mice. Arzneimittelforschung 1996; 46(10): 972-5. [PMID: 8931891].
El Hamss R, Idaomar M, Alonso-Moraga A, Muñoz Serrano A. Antimutagenic properties of bell and black peppers. Food Chem Toxicol 2003; 41(1): 41-7. [http://dx.doi.org/10.1016/S0278-6915(02)00216-8]. [PMID: 12453727].
Thiel A, Buskens C, Woehrle T, et al. Black pepper constituent piperine: Genotoxicity studies in vitro and in vivo. Food Chem Toxicol 2014; 66: 350-7. [http://dx.doi.org/10.1016/j.fct.2014.01.056]. [PMID: 24525095].
Sponchiado G, Adam ML, Silva CD, et al. Quantitative genotoxicity assays for analysis of medicinal plants: A systematic review. J Ethnopharmacol 2016; 178: 289-96. [http://dx.doi.org/10.1016/j.jep.2015.10.026]. [PMID: 26680588].
Selvendiran K, Padmavathi R, Magesh V, Sakthisekaran D. Preliminary study on inhibition of genotoxicity by piperine in mice. Fitoterapia 2005; 76(3-4): 296-300. [http://dx.doi.org/10.1016/j.fitote.2005.03.016]. [PMID: 15890459].
Selvendiran K, Prince Vijeya Singh J, Sakthisekaran D. In vivo effect of piperine on serum and tissue glycoprotein levels in benzo(a)pyrene induced lung carcinogenesis in Swiss albino mice. Pulm Pharmacol Ther 2006; 19(2): 107-11. [http://dx.doi.org/10.1016/j.pupt.2005.04.002]. [PMID: 15975841].
da Silva Cardoso V, Vermelho AB, Ribeiro de Lima CA, et al. Antigenotoxic effect of piperine in broiler chickens intoxicated with Aflatoxin B1. Toxins (Basel) 2016; 8(11): 316. [http://dx.doi.org/10.3390/toxins8110316]. [PMID: 27809242].
Dogra RK, Khanna S, Shanker R. Immunotoxicological effects of piperine in mice. Toxicology 2004; 196(3): 229-36. [http://dx.doi.org/10.1016/j.tox.2003.10.006]. [PMID: 15036749].
Pathak N, Khandelwal S. Cytoprotective and immunomodulating properties of piperine on murine splenocytes: An in vitro study. Eur J Pharmacol 2007; 576(1-3): 160-70. [http://dx.doi.org/10.1016/j.ejphar.2007.07.033]. [PMID: 17706638].
Pathak N, Khandelwal S. Comparative efficacy of piperine, curcumin and picroliv against Cd immunotoxicity in mice. Biometals 2008; 21(6): 649-61. [http://dx.doi.org/10.1007/s10534-008-9150-y]. [PMID: 18566892].
Sankar P, Ramya K. Protective effects of piperine on cypermethrin-induced haematological toxicity in rats. Int J Sci Environ Technol 2017; 6: 2971-4.
Kumar A, Sasmal D, Sharma N. Immunomodulatory role of piperine in deltamethrin induced thymic apoptosis and altered immune functions. Environ Toxicol Pharmacol 2015; 39(2): 504-14. [http://dx.doi.org/10.1016/j.etap.2014.12.021]. [PMID: 25682002].
Daware MB, Mujumdar AM, Ghaskadbi S. Reproductive toxicity of piperine in Swiss albino mice. Planta Med 2000; 66(3): 231-6. [http://dx.doi.org/10.1055/s-2000-8560]. [PMID: 10821048].
D’cruz SC, Mathur PP. Effect of piperine on the epididymis of adult male rats. Asian J Androl 2005; 7(4): 363-8. [http://dx.doi.org/10.1111/j.1745-7262.2005.00059.x]. [PMID: 16281082].
Chen X, Ge F, Liu J, et al. Diverged effects of piperine on testicular development: Stimulating Leydig cell development but inhibiting spermatogenesis in rats. Front Pharmacol 2018; 9: 244. [http://dx.doi.org/10.3389/fphar.2018.00244]. [PMID: 29643806].
Gurley BJ, Fifer EK, Gardner Z. Pharmacokinetic herb-drug interactions (part 2): Drug interactions involving popular botanical dietary supplements and their clinical relevance. Planta Med 2012; 78(13): 1490-514. [http://dx.doi.org/10.1055/s-0031-1298331]. [PMID: 22565299].
Majeed M, Badmaev V, Rajendran R. inventors; Sabinsa Corporation, asignee Use of piperine as a bioavailability enhancer. United States patent US 5744161 1998.Apr;.
Izzo AA, Capasso R, Pinto L, Di Carlo G, Mascolo N, Capasso F. Effect of vanilloid drugs on gastrointestinal transit in mice. Br J Pharmacol 2001; 132(7): 1411-6. [http://dx.doi.org/10.1038/sj.bjp.0703975]. [PMID: 11264233].
Sharma P, Varma MV, Chawla HP, Panchagnula R. In situ and in vivo efficacy of peroral absorption enhancers in rats and correlation to in vitro mechanistic studies. Farmaco 2005; 60(11-12): 874-83. [http://dx.doi.org/10.1016/j.farmac.2005.08.007]. [PMID: 16243320].
Prakash UN, Srinivasan K. Beneficial influence of dietary spices on the ultrastructure and fluidity of the intestinal brush border in rats. Br J Nutr 2010; 104(1): 31-9. [http://dx.doi.org/10.1017/S0007114510000334]. [PMID: 20178671].
Lee SH, Kim HY, Back SY, Han H-K. Piperine-mediated drug interactions and formulation strategy for piperine: Recent advances and future perspectives. Expert Opin Drug Metab Toxicol 2018; 14(1): 43-57. [http://dx.doi.org/10.1080/17425255.2018.1418854]. [PMID: 29250980].
Bhardwaj RK, Glaeser H, Becquemont L, Klotz U, Gupta SK, Fromm MF. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002; 302(2): 645-50. [http://dx.doi.org/10.1124/jpet.102.034728]. [PMID: 12130727].
Han Y, Chin Tan TM, Lim LY. In vitro and in vivo evaluation of the effects of piperine on P-gp function and expression. Toxicol Appl Pharmacol 2008; 230(3): 283-9. [http://dx.doi.org/10.1016/j.taap.2008.02.026]. [PMID: 18417181].
Zhang W, Han Y, Lim SL, Lim LY. Dietary regulation of P-gp function and expression. Expert Opin Drug Metab Toxicol 2009; 5(7): 789-801. [http://dx.doi.org/10.1517/17425250902997967]. [PMID: 19545213].
Jhanwar B, Gupta SS. Biopotentiation using herbs: Novel technique for poor bioavailable drugs. Int J Pharm Tech Res 2014; 6: 443-54.
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 Interact 1991; 9(1): 23-30. [http://dx.doi.org/10.1515/DMDI.1991.9.1.23]. [PMID: 1893751].
Singh A, Rao AR. Evaluation of the modulatory influence of black pepper (Piper nigrum, L.) on the hepatic detoxication system. Cancer Lett 1993; 72(1-2): 5-9. [http://dx.doi.org/10.1016/0304-3835(93)90003-R]. [PMID: 8402574].
Sevrioukova IF, Poulos TL. Understanding the mechanism of cytochrome P450 3A4: Recent advances and remaining problems. Dalton Trans 2013; 42(9): 3116-26. [http://dx.doi.org/10.1039/C2DT31833D]. [PMID: 23018626].
Oda S, Fukami T, Yokoi T, Nakajima M. A comprehensive review of UDP-glucuronosyltransferase and esterases for drug development. Drug Metab Pharmacokinet 2015; 30(1): 30-51. [http://dx.doi.org/10.1016/j.dmpk.2014.12.001]. [PMID: 25760529].
Bedada SK, Boga PK. The influence of piperine on the pharmacokinetics of fexofenadine, a P-glycoprotein substrate, in healthy volunteers. Eur J Clin Pharmacol 2017; 73(3): 343-9. [http://dx.doi.org/10.1007/s00228-016-2173-3]. [PMID: 27981349].
Hewlings SJ, Kalman DS. Curcumin: A Review of Its’ Effects on Human Health. Foods 2017; 6(10): 92. [http://dx.doi.org/10.3390/foods6100092]. [PMID: 29065496].
Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 1998; 64(4): 353-6. [http://dx.doi.org/10.1055/s-2006-957450]. [PMID: 9619120].
Panahi Y, Khalili N, Sahebi E, et al. Antioxidant effects of curcuminoids in patients with type 2 diabetes mellitus: A randomized controlled trial. Inflammopharmacology 2017; 25(1): 25-31. [http://dx.doi.org/10.1007/s10787-016-0301-4]. [PMID: 27928704].
Panahi Y, Hosseini MS, Khalili N, Naimi E, Majeed M, Sahebkar A. Antioxidant and anti-inflammatory effects of curcuminoid-piperine combination in subjects with metabolic syndrome: A randomized controlled trial and an updated meta-analysis. Clin Nutr 2015; 34(6): 1101-8. [http://dx.doi.org/10.1016/j.clnu.2014.12.019]. [PMID: 25618800].
Delecroix B, Abaïdia AE, Leduc C, Dawson B, Dupont G. Curcumin and Piperine Supplementation and Recovery Following Exercise Induced Muscle Damage: A Randomized Controlled Trial. J Sports Sci Med 2017; 16(1): 147-53. [PMID: 28344463].
Kaur GCM. Amelioration of obesity, glucose intolerance, and oxidative stress in high-fat diet and low-dose streptozotocin-induced diabetic rats by combination consisting of “curcumin with piperine and quercetin”. ISRN Pharmacol 2012; 2012957283 [http://dx.doi.org/10.5402/2012/957283]. [PMID: 22474599].
Arcaro CA, Gutierres VO, Assis RP, et al. Piperine, a natural bioenhancer, nullifies the antidiabetic and antioxidant activities of curcumin in streptozotocin-diabetic rats. PLoS One 2014; 9(12)e113993 [http://dx.doi.org/10.1371/journal.pone.0113993]. [PMID: 25469699].
Polley KR, Jenkins N, O’Connor P, McCully K. Influence of exercise training with resveratrol supplementation on skeletal muscle mitochondrial capacity. Appl Physiol Nutr Metab 2016; 41(1): 26-32. [http://dx.doi.org/10.1139/apnm-2015-0370]. [PMID: 26638911].
Johnson JJ, Nihal M, Siddiqui IA, et al. Enhancing the bioavailability of resveratrol by combining it with piperine. Mol Nutr Food Res 2011; 55(8): 1169-76. [http://dx.doi.org/10.1002/mnfr.201100117]. [PMID: 21714124].
Badmaev V, Majeed M, Edward PN. Piperine, an alkaloid derived from black pepper, increases serum response of beta-carotene during 14 days of oral beta-carotenesupplementation. Nutr Res 1999; 19: 381-8. [http://dx.doi.org/10.1016/S0271-5317(99)00007-X].
Badmaev V, Majeed M, Prakash L. Piperine derived from black pepper increases the plasma levels of coenzyme Q10 following oral supplementation. J Nutr Biochem 2000; 11(2): 109-13. [http://dx.doi.org/10.1016/S0955-2863(99)00074-1]. [PMID: 10715596].
Pelicano H, Carney D, Huang P. ROS stress in cancer cells and therapeutic implications. Drug Resist Updat 2004; 7(2): 97-110. [http://dx.doi.org/10.1016/j.drup.2004.01.004]. [PMID: 15158766].
Waris G, Ahsan H. Reactive oxygen species: Role in the development of cancer and various chronic conditions. J Carcinog 2006; 5: 14. [http://dx.doi.org/10.1186/1477-3163-5-14]. [PMID: 16689993].
Belaya I, Suwa M, Chen T, et al. Long-Term Exercise Protects against Cellular Stresses in Aged Mice. Oxid Med Cell Longev 2018; 20182894247 [http://dx.doi.org/10.1155/2018/2894247]. [PMID: 29765493].
Hulmi JJ, Isola V, Suonpää M, et al. The Effects of Intensive Weight Reduction on Body Composition and Serum Hormones in Female Fitness Competitors. Front Physiol 2017; 7: 689. [http://dx.doi.org/10.3389/fphys.2016.00689]. [PMID: 28119632].
Radak Z, Zhao Z, Koltai E, Ohno H, Atalay M. Oxygen consumption and usage during physical exercise: The balance between oxidative stress and ROS-dependent adaptive signaling. Antioxid Redox Signal 2013; 18(10): 1208-46. [http://dx.doi.org/10.1089/ars.2011.4498]. [PMID: 22978553].
Atalay M, Lappalainen J, Sen CK. Dietary antioxidants for the athlete. Curr Sports Med Rep 2006; 5(4): 182-6. [http://dx.doi.org/10.1097/01.CSMR.0000306504.71105.6e]. [PMID: 16822339].
Srinivasan K. Antioxidant potential of spices and their active constituents. Crit Rev Food Sci Nutr 2014; 54(3): 352-72. [http://dx.doi.org/10.1080/10408398.2011.585525]. [PMID: 24188307].
Mittal R, Gupta RL. In vitro antioxidant activity of piperine. Methods Find Exp Clin Pharmacol 2000; 22(5): 271-4. [http://dx.doi.org/10.1358/mf.2000.22.5.796644]. [PMID: 11031726].
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. [http://dx.doi.org/10.1023/A:1017930708099]. [PMID: 11936843].
Verma N, Bal S, Gupta R, Aggarwal N, Yadav A. Antioxidative Effects of Piperine against Cadmium-Induced Oxidative Stress in Cultured Human Peripheral Blood Lymphocytes. J Diet Suppl 2018; 9: 1-12. Epub ahead of print [http://dx.doi.org/10.1080/19390211.2018.1481485]. [PMID: 30299203].
Rauscher FM, Sanders RA, Watkins JB III. Effects of piperine on antioxidant pathways in tissues from normal and streptozotocin-induced diabetic rats. J Biochem Mol Toxicol 2000; 14(6): 329-34. [http://dx.doi.org/10.1002/1099-0461(2000)14:6<329:AID-JBT5>3.0.CO;2-G]. [PMID: 11083086].
Whitehouse S, Chen PL, Greenshields AL, Nightingale M, Hoskin DW, Bedard K. Resveratrol, piperine and apigenin differ in their NADPH-oxidase inhibitory and reactive oxygen species-scavenging properties. Phytomedicine 2016; 23(12): 1494-503. [http://dx.doi.org/10.1016/j.phymed.2016.08.011]. [PMID: 27765370].
Sunila ES, Kuttan G. Immunomodulatory and antitumor activity of Piper longum Linn. and piperine. J Ethnopharmacol 2004; 90(2-3): 339-46. [http://dx.doi.org/10.1016/j.jep.2003.10.016]. [PMID: 15013199].
Manayi A, Nabavi SM, Setzer WN, Jafari S. Piperine as a potential anti-cancer agent: A review on preclinical studies. Curr Med Chem 2018; 25(37): 4918-28. [http://dx.doi.org/10.2174/0929867324666170523120656]. [PMID: 28545378].
Rather RA, Bhagat M. Cancer Chemoprevention and Piperine: Molecular Mechanisms and Therapeutic Opportunities. Front Cell Dev Biol 2018; 6: 10. [http://dx.doi.org/10.3389/fcell.2018.00010]. [PMID: 29497610].
Singh J, Reen RK, Wiebel FJ. Piperine, a major ingredient of black and long peppers, protects against AFB1-induced cytotoxicity and micronuclei formation in H4IIEC3 rat hepatoma cells. Cancer Lett 1994; 86(2): 195-200. [http://dx.doi.org/10.1016/0304-3835(94)90078-7]. [PMID: 7982207].
Reen RK, Wiebel FJ, Singh J. Piperine inhibits aflatoxin B1-induced cytotoxicity and genotoxicity in V79 Chinese hamster cells genetically engineered to express rat cytochrome P4502B1. J Ethnopharmacol 1997; 58(3): 165-73. [http://dx.doi.org/10.1016/S0378-8741(97)00104-9]. [PMID: 9421252].
Selvendiran K, Singh JP, Krishnan KB, Sakthisekaran D. Cytoprotective effect of piperine against benzo[a]pyrene induced lung cancer with reference to lipid peroxidation and antioxidant system in Swiss albino mice. Fitoterapia 2003; 74(1-2): 109-15. [http://dx.doi.org/10.1016/S0367-326X(02)00304-0]. [PMID: 12628402].
Selvendiran K, Banu SM, Sakthisekaran D. Protective effect of piperine on benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice. Clin Chim Acta 2004; 350(1-2): 73-8. [http://dx.doi.org/10.1016/j.cccn.2004.07.004]. [PMID: 15530462].
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): 264-7. [http://dx.doi.org/10.1016/j.biopha.2003.08.027]. [PMID: 15183854].
Pradeep CR, Kuttan G. Effect of piperine on the inhibition of lung metastasis induced B16F-10 melanoma cells in mice. Clin Exp Metastasis 2002; 19(8): 703-8. [http://dx.doi.org/10.1023/A:1021398601388]. [PMID: 12553376].
Bezerra DP, Castro FO, Alves APNN, et al. In vivo growth-inhibition of Sarcoma 180 by piplartine and piperine, two alkaloid amides from Piper. Braz J Med Biol Res 2006; 39(6): 801-7. [http://dx.doi.org/10.1590/S0100-879X2006000600014]. [PMID: 16751987].
Bezerra DP, de Castro FO, Alves APNN, et al. In vitro and in vivo antitumor effect of 5-FU combined with piplartine and piperine. J Appl Toxicol 2008; 28(2): 156-63. [http://dx.doi.org/10.1002/jat.1261]. [PMID: 17541943].
Lai LH, Fu QH, Liu Y, et al. Piperine suppresses tumor growth and metastasis in vitro and in vivo in a 4T1 murine breast cancer model. Acta Pharmacol Sin 2012; 33(4): 523-30. [http://dx.doi.org/10.1038/aps.2011.209]. [PMID: 22388073].
Hwang YP, Yun HJ, Kim HG, et al. Suppression of phorbol-12-myristate-13-acetate-induced tumor cell invasion by piperine via the inhibition of PKCα/ERK1/2-dependent matrix metalloproteinase-9 expression. Toxicol Lett 2011; 203(1): 9-19. [http://dx.doi.org/10.1016/j.toxlet.2011.02.013]. [PMID: 21354279].
Do MT, Kim HG, Choi JH, et al. Antitumor efficacy of piperine in the treatment of human HER2-overexpressing breast cancer cells. Food Chem 2013; 141(3): 2591-9. [http://dx.doi.org/10.1016/j.foodchem.2013.04.125]. [PMID: 23870999].
Martin-Cordero C, Leon-Gonzalez AJ, Calderon-Montano JM, Burgos-Moron E, Lopez-Lazaro M. Pro-oxidant natural products as anticancer agents. Curr Drug Targets 2012; 13(8): 1006-28. [http://dx.doi.org/10.2174/138945012802009044]. [PMID: 22594470].
Srinivasan MR, Satyanarayana MN. Effect of black pepper (Piper Nigrum Linn.) and piperine on growth, blood constituents and organ eights in rats. Nutr Rep Int 1981; 23: 871-6.
Bhat GB, Chandrasekhara N. Lack of adverse influence of black pepper, its Oleoresin and piperine in the weanling rat. J Food Saf 1986; 7: 215-23. [http://dx.doi.org/10.1111/j.1745-4565.1986.tb00543.x].
Pachauri M, Gupta ED, Ghosh PC. Piperine loaded PEG-PLGA nanoparticles: Preparation, characterization and targeted delivery for adjuvant breast cancer chemotherapy. J Drug Deliv Sci Technol 2015; 29: 269-82. [http://dx.doi.org/10.1016/j.jddst.2015.08.009].
Jain S, Meka SRK, Chatterjee K. Engineering a piperine eluting nanofibrous patch for cancer treatment. ACS Biomater Sci Eng 2016; 2: 1376-85. [http://dx.doi.org/10.1021/acsbiomaterials.6b00297].
Elnaggar YS, Etman SM, Abdelmonsif DA, Abdallah OY. Intranasal piperine-loaded chitosan nanoparticles as brain-targeted therapy in Alzheimer’s disease: Optimization, biological efficacy, and potential toxicity. J Pharm Sci 2015; 104: 3544-56. [http://dx.doi.org/10.1002/jps.24557].
Yusuf M, Khan M, Khan RA, Ahmed B. Preparation, characterization, in vivo and biochemical evaluation of brain targeted Piperine solid lipid nanoparticles in an experimentally induced Alzheimer’s disease model. J Drug Target 2013; 21(3): 300-11. [http://dx.doi.org/10.3109/1061186X.2012.747529]. [PMID: 23231324].
Pentak D. In vitro spectroscopic study of piperine-encapsulated nanosize liposomes. Eur Biophys J 2016; 45(2): 175-86. [http://dx.doi.org/10.1007/s00249-015-1086-x]. [PMID: 26493066].
Priprem A, Chonpathompikunlert P, Sutthiparinyanont S, Wattanathorn J. Antidepressant and cognitive activities of intranasal piperine-encapsulated liposomes. Adv Biosci Biotechnol 2011; 2: 108-16. [http://dx.doi.org/10.4236/abb.2011.22017].
Shao B, Cui C, Ji H, et al. Enhanced oral bioavailability of piperine by self-emulsifying drug delivery systems: In vitro, in vivo and in situ intestinal permeability studies. Drug Deliv 2015; 22(6): 740-7. [http://dx.doi.org/10.3109/10717544.2014.898109]. [PMID: 24670090].
Boddupalli BM, Ramani R, Subramaniam B, Anisetti RN. In vitro and in vivo evaluation of hepato- protection and anti-ulcer activities of piperine gastro retentive micropspheres. Asian Pac J Trop Biomed 2012; 2: 1237-40. [http://dx.doi.org/10.1016/S2221-1691(12)60392-X].
Sezgin V, Bayraktar O. assignee. Development of curcumin and piperine loaded double-layered biopolymer based nano delivery systems by using electrospray/coating method. United States patent US 20180028447 2015.Apr;.
Hoffman A, Domb AJ, Elgart A, Cherniakov I. inventors; Formulation and method for increasing oral bioavailability of drugs. United States patent US20140348926 2004. Nov;.
Thrower DW inventor. Pharmaceutical oral dose formulation and composition of matter. US2018/0071214 A1 2018. Mar;.
Gabriele J, Teris M, Baranowski D. inventors; DELIVRA INC., assignee Transdermal formulations for delivery of capsaicinoids. United States patent US 20180221427 2018.Sep;.

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Year: 2019
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DOI: 10.2174/1381612825666190701150803
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