Generic placeholder image

Current Bioactive Compounds


ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Review Article

Therapeutic Benefits of Piper nigrum: A Review

Author(s): Banishree Majumdar, Rishabha Malviya* and Akanksha Sharma

Volume 18, Issue 5, 2022

Published on: 14 February, 2022

Article ID: e221221199275 Pages: 8

DOI: 10.2174/1573407218666211222143301

Price: $65


This manuscript aims to describe the various pharmacological activities of Piper nigrum. Pepper is a common spice of the plant which is used as spice in preparation of various foods. Pepper production is centered in Kerela, followed by Karnataka and Maharashtra in India. Other big pepper-producing countries include Indonesia, Malaysia, Brazil, Vietnam, and Sri Lanka. It has various pharmacological activities which is why it is used in the treatment of different diseases. The manuscript mainly describes the antituberculosis, anticonvulsant, analgesic, antipyretic, anti- inflammatory, antimicrobial, antioxidant, gastrointestinal and anticancer activities of Piper nigrum. The manuscript also describes the various studies related to the pharmacological activities of Piper nigrum. It is concluded from the manuscript that Piper nigrum has great efficacy in the treatment of various diseases.

Keywords: Piper nigrum, pharmacological activity, antituberculosis, anticonvulsant, analgesic, anti-inflammatory.

Graphical Abstract
Joshi, D.R.; Shrestha, A.C.; Adhikari, N. A review on diversified use of the king of spices: Piper nigrum (Black Pepper). Int. J. Pharm. Sci. Res., 2018, 9(10), 4089-4101.
Lee, E.B.; Shin, K.H.; Woo, W.S. Pharmacological study on piperine. Arch. Pharm. Res., 1984, 7(2), 127-132.
Stojanovic-Radic, Z.; Pejcic, M.; Dimitrijevic, M.; Aleksic, A.; V Anil Kumar, N.; Salehi, B.; C Cho, W.; Sharifi-Rad, J. Piperine-A major principle of black pepper: A review of its bioactivity and studies. Appl. Sci. (Basel), 2019, 9(20), 1-29.
Takooree, H.; Aumeeruddy, M.Z.; Rengasamy, K.R.R.; Venugopala, K.N.; Jeewon, R.; Zengin, G.; Mahomoodally, M.F. A systematic review on black pepper (Piper nigrum L.): from folk uses to pharmacological applications. Crit. Rev. Food Sci. Nutr., 2019, 59(sup1), S210-S243.
[] [PMID: 30740986]
Vijayakumar, R.S.; 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.
[] [PMID: 15231065]
Ighodaro, O.M.; Akinloye, O.A. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alex. J. Med., 2018, 54(4), 287-293.
Singh, B. Critical review of maricha (Piper nigrum Linn) in brihat trayi with special reference to nighantus. Dev Sanskriti Interdiscip. Int. J., 2016, 7, 65-71.
Carp, O.E.; Moraru, A.; Pinteala, M.; Arvinte, A. Electrochemical behaviour of piperine. Comparison with control antioxidants. Food Chem., 2021, 339, 128110.
[] [PMID: 33152887]
Panahi, Y.; Hosseini, M.S.; 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), 1101-1108.
[] [PMID: 25618800]
Rauscher, F.M.; Sanders, R.A.; Watkins, J.B., III. Effects of piperine on antioxidant pathways in tissues from normal and streptozotocin-induced diabetic rats. J. Biochem. Mol. Toxicol., 2000, 14(6), 329-334.
[<329::AID-JBT5>3.0.CO;2-G] [PMID: 11083086]
Ahmad, N.; Fazal, H.; Abbasi, B.H.; Farooq, S.; Ali, M.; Khan, M.A. Biological role of Piper nigrum L.(Black pepper): A review. Asian Pac. J. Trop. Biomed., 2012, 2(3), 1945-1953.
Aldaly, Z.T. Antimicrobial activity of piperine purified from Piper nigrum. J. Basrah Res. (Sci.), 2010, 36, 54-61.
Liu, Q.; Meng, X.; Li, Y.; Zhao, C.N.; Tang, G.Y.; Li, H.B. Antibacterial and antifungal activities of spices. Int. J. Mol. Sci., 2017, 18(6), 1-62.
[] [PMID: 28621716]
Hikal, D.M. Antibacterial activity of piperine and black pepper oil. Biosci. Biotechnol. Res. Asia, 2018, 15(4), 871-878.
Sharma, S.; Kumar, M.; Sharma, S.; Nargotra, A.; Koul, S.; Khan, I.A. Piperine as an inhibitor of Rv1258c, a putative multidrug efflux pump of Mycobacterium tuberculosis. J. Antimicrob. Chemother., 2010, 65(8), 1694-1701.
[] [PMID: 20525733]
Moraru, A.C.; Rosca, I.; Craciun, B.; Nicolesu, A.; Chiriac, A.E.; Voicu, V. Insight of the antimicrobial activity of piperine extracted from Piper nigrum L. Farmacia, 2019, 67(6), 1099-1105.
Mirza, Z.M.; Kumar, A.; Kalia, N.P.; Zargar, A.; Khan, I.A. Piperine as an inhibitor of the MdeA efflux pump of Staphylococcus aureus. J. Med. Microbiol., 2011, 60(Pt 10), 1472-1478.
[] [PMID: 21680766]
Mgbeahuruike, E.E.; Stålnacke, M.; Vuorela, H.; Holm, Y. Antimicrobial and synergistic effects of commercial piperine and piperlongumine in combination with conventional antimicrobials. Antibiotics (Basel), 2019, 8(2), 1-12.
[] [PMID: 31060239]
Tasleem, F.; Azhar, I.; Ali, S.N.; Perveen, S.; Mahmood, Z.A. Analgesic and anti-inflammatory activities of Piper nigrum L. Asian Pac. J. Trop. Med., 2014, 7S1, S461-S468.
Crofford, L.J. Use of NSAIDs in treating patients with arthritis. Arthritis Res. Ther., 2013, 15(3)(Suppl. 3), S2.
[] [PMID: 24267197]
Raman, G.; Gaikar, V.G. Extraction of piperine from Piper nigrum (black pepper) by hydrotropic solubilization. Ind. Eng. Chem. Res., 2002, 41(12), 2966-2976.
Sabina, E.P.; Nasreen, A.; Vedi, M.; Rasool, M. Analgesic, antipyretic and ulcerogenic effects of piperine: an active ingredient of pepper. J. Pharm. Sci. Res., 2013, 5(10), 8-11.
Dhargawe, N.; Mahakalkar, S.; Mohod, B.; Raj, J.P. Evaluation of analgesic, anti-inflammatory, and antipyretic activity of piperine: An experimental study. Pharmacogn. Rev., 2020, 12(2), 176-180.
Sudjarwo, S.A. The potency of piperine as antiinflammatory and analgesic in rats and mice. Folia Medica Indonesiana, 2005, 41(3), 190-194.
Damanhouri, Z.A.; Ahmad, A. A review on therapeutic potential of Piper nigrum L. (Black Pepper): The king of spices. Med. Aromat. Plants, 2014, 3(3), 1-6.
Mujumdar, A.M.; Dhuley, J.N.; Deshmukh, V.K.; Raman, P.H.; Naik, S.R. Anti-inflammatory activity of piperine. Jpn. J. Med. Sci. Biol., 1990, 43(3), 95-100.
[] [PMID: 2283727]
Mishra, A.; Punia, J.K.; Bladen, C.; Zamponi, G.W.; Goel, R.K. Anticonvulsant mechanisms of piperine, a piperidine alkaloid. Channels (Austin), 2015, 9(5), 317-323.
[] [PMID: 26542628]
Sirven, J.I. Epilepsy: A spectrum disorder. Cold Spring Harb. Perspect. Med., 2015, 5(9), a022848.
[] [PMID: 26328931]
da Cruz, G.M.P.; Felipe, C.F.B.; Scorza, F.A.; da Costa, M.A.C.; Tavares, A.F.; Menezes, M.L.F.; de Andrade, G.M.; Leal, L.K.A.; Brito, G.A.C.; da Graça Naffah-Mazzacoratti, M.; Cavalheiro, E.A.; de Barros Viana, G.S. Piperine decreases pilocarpine-induced convulsions by GABAergic mechanisms. Pharmacol. Biochem. Behav., 2013, 104, 144-153.
[] [PMID: 23313550]
Aukunuru, J.; Eedula, K.; Pasham, V.; Katla, V.; Reddy, S.K. Synthesis of novel piperonal derivatives and evaluation of their anticonvulsant activity using a nanoparticular formulation. Int. J. Pharm. Sci. Nanotechnol., 2009, 2, 435-442.
Anissian, D.; Ghasemi-Kasman, M.; Khalili-Fomeshi, M.; Akbari, A.; Hashemian, M.; Kazemi, S.; Moghadamnia, A.A. Piperine-loaded chitosan-STPP nanoparticles reduce neuronal loss and astrocytes activation in chemical kindling model of epilepsy. Int. J. Biol. Macromol., 2018, 107(Pt A), 973-983.
Pal, A.; Nayak, S.; Sahu, P.K.; Swain, T. Piperine protects epilepsy associated depression: A study on role of monoamines. Eur. Rev. Med. Pharmacol. Sci., 2011, 15(11), 1288-1295.
[PMID: 22195361]
Mori, A.; Kabuto, H.; Pei, Y.Q. Effects of piperine on convulsions and on brain serotonin and catecholamine levels in E1 mice. Neurochem. Res., 1985, 10(9), 1269-1275.
[] [PMID: 4058659]
Wang, C.; Cai, Z.; Wang, W.; Wei, M.; Kou, D.; Li, T.; Yang, Z.; Guo, H.; Le, W.; Li, S. Piperine attenuates cognitive impairment in an experimental mouse model of sporadic Alzheimer’s disease. J. Nutr. Biochem., 2019, 70, 147-155.
[] [PMID: 31207354]
Liu, G.Q.; Garattini, S. Stimulation of serotonin synthesis in rat brain after administration of antiepilepsirine, an antiepileptic piperine derivative. Chin. Med. J. (Engl.), 1986, 99(5), 411-416.
[PMID: 2433103]
Priprem, A.; Chonpathompikunlert, P.; Sutthiparinyanont, S.; Wattanathorn, J. Antidepressant and cognitive activities of intranasal piperine-encapsulated liposomes. Adv. Biosci. Biotechnol., 2011, 2(02), 108-116.
Saraogi, P.; Vohora, D.; Khanam, R.; Pillai, K.K. Combination therapy of piperine and phenytoin in maximal electroshock induced seizures in mice: Isobolographic and biochemical analysis. Drug Res. (Stuttg.), 2013, 63(6), 311-318.
[] [PMID: 23529722]
Hegeto, L.A.; Caleffi-Ferracioli, K.R.; Perez de Souza, J.; Almeida, A.L.D.; Nakamura de Vasconcelos, S.S.; Barros, I.L.E.; Canezin, P.H.; Campanerut-Sá, P.A.Z.; Scodro, R.B.L.; Siqueira, V.L.D.; Teixeira, J.J.V.; Cardoso, R.F. Promising antituberculosis activity of piperine combined with antimicrobials: A systematic review. Microb. Drug Resist., 2019, 25(1), 120-126.
[] [PMID: 30096263]
Zafar, F.; Jahan, N.; Bhatti, H.N. Increased oral bioavailability of piperine from an optimized Piper nigrum nanosuspension. Planta Med., 2019, 85(3), 249-257.
[] [PMID: 30357764]
Hegeto, L.A.; Caleffi-Ferracioli, K.R.; Nakamura-Vasconcelos, S.S.; Almeida, A.L.; Baldin, V.P.; Nakamura, C.V.; Siqueira, V.L.D.; Scodro, R.B.L.; Cardoso, R.F. In vitro combinatory activity of piperine and anti-tuberculosis drugs in Mycobacterium tuberculosis. Tuberculosis (Edinb.), 2018, 111, 35-40.
[] [PMID: 30029912]
Murase, L.S.; Perez de Souza, J.V.; Meneguello, J.E.; Seixas, F.A.V.; Hegeto, L.A.; Scodro, R.B.L.; Siqueira, V.L.D.; Caleffi Ferracioli, K.R.; Cardoso, R.F. Possible binding of piperine in Mycobacterium tuberculosis RNA polymerase and rifampin synergism. Antimicrob. Agents Chemother., 2019, 63(11), 1-7.
[] [PMID: 31481438]
Birdi, T.; D’souza, D.; Tolani, M.; Daswani, P.; Nair, V.; Tetali, P.; Toro, J.C.; Hoffner, S. Assessment of the activity of selected Indian medicinal plants against Mycobacterium tuberculosis: A preliminary screening using the Microplate Alamar Blue Assay. European J. Med. Plants, 2012, 308-323.
Raja, A.; Kapur, A.; Fijju, M.; Salique, M. In vitro studies on Efflux pump Inhibition of Catharanthus roseus and piperine against ofloxacin resistant M. tuberculosis. Int. J. Pharm. Sci. Invent., 2015, 4(9), 32-37.
Bajad, S.; Bedi, K.L.; Singla, A.K.; Johri, R.K. Antidiarrhoeal activity of piperine in mice. Planta Med., 2001, 67(3), 284-287.
[] [PMID: 11345706]
Mehmood, M.H.; Gilani, A.H. Pharmacological basis for the medicinal use of black pepper and piperine in gastrointestinal disorders. J. Med. Food, 2010, 13(5), 1086-1096.
[] [PMID: 20828313]
Bajad, S.; Bedi, K.L.; Singla, A.K.; Johri, R.K. Piperine inhibits gastric emptying and gastrointestinal transit in rats and mice. Planta Med., 2001, 67(2), 176-179.
[] [PMID: 11301872]
Chen, S.; Li, Q.; McClements, D.J.; Han, Y.; Dai, L.; Mao, L.; Gao, Y. Co-delivery of curcumin and piperine in zein-carrageenan core-shell nanoparticles: Formation, structure, stability and in vitro gastrointestinal digestion. Food Hydrocoll., 2020, 99.
Khatri, S.; Awasthi, R. Piperine containing floating microspheres: An approach for drug targeting to the upper gastrointestinal tract. Drug Deliv. Transl. Res., 2016, 6(3), 299-307.
[] [PMID: 26902907]
Rashid, A.H.U.; Watanabe, S.; Kikkawa, T.; Guo, X. Interference suppression of wireless interconnection in Si integrated antenna. Proceedings of the IEEE 2002 International Interconnect Technology Conference, 2002, pp. 173-175.
Umadevi, P.; Deepti, K.; Venugopal, D.V. Synthesis, anticancer and antibacterial activities of piperine analogs. Med. Chem. Res., 2013, 22(11), 5466-5471.
Bolat, Z.B.; Islek, Z.; Demir, B.N.; Yilmaz, E.N.; Sahin, F.; Ucisik, M.H. Curcumin-and Piperine-loaded emulsomes as combinational treatment approach enhance the anticancer activity of Curcumin on HCT116 colorectal cancer model. Front. Bioeng. Biotechnol., 2020, 8, 50.
[] [PMID: 32117930]
Li, X.; Shi, J.R.; Yang, M.S.; Lu, Y.; Chen, L.; Cao, H.R. Study on the extraction, geometry structure and spectral characterization of piperine alkaloid. Guang pu xue yu Guang pu fen xi= Guang pu, 2016, 36(7), 2082-2088.
Li, X.; Yu, S.; Yang, M.; Xu, C.; Wang, Y.; Chen, L. Electronic structure analysis of glycine oligopeptides and glycine–tryptophan oligopeptides. Physica E, 2014, 57, 63-68.
Li, X.; Yang, M.; Shi, X.; Chu, X.; Chen, L.; Wu, Q.; Wang, Y. Effect of the intramolecular hydrogen bond on the spectral and optical properties in chitosan oligosaccharide. Physica E, 2015, 69, 237-242.
Sriwiriyajan, S.; Tedasen, A.; Lailerd, N.; Boonyaphiphat, P.; Nitiruangjarat, A.; Deng, Y.; Graidist, P. Anticancer and cancer prevention effects of piperine-free Piper nigrum extract on N-nitrosomethylurea-induced mammary tumorigenesis in rats. Cancer Prev. Res. (Phila.), 2016, 9(1), 74-82.
[] [PMID: 26511488]
Yaffe, P.B.; Doucette, C.D.; Walsh, M.; Hoskin, D.W. Piperine impairs cell cycle progression and causes reactive oxygen species-dependent apoptosis in rectal cancer cells. Exp. Mol. Pathol., 2013, 94(1), 109-114.
[] [PMID: 23063564]
Yaffe, P.B.; Power Coombs, M.R.; Doucette, C.D.; Walsh, M.; Hoskin, D.W. Piperine, an alkaloid from black pepper, inhibits growth of human colon cancer cells via G1 arrest and apoptosis triggered by endoplasmic reticulum stress. Mol. Carcinog., 2015, 54(10), 1070-1085.
[] [PMID: 24819444]
Gunasekaran, V.; Elangovan, K.; Niranjali Devaraj, S. Targeting hepatocellular carcinoma with piperine by radical-mediated mitochondrial pathway of apoptosis: An in vitro and in vivo study. Food Chem. Toxicol., 2017, 105, 106-118.
[] [PMID: 28341137]
Siddiqui, S.; Ahamad, M.S.; Jafri, A.; Afzal, M.; Arshad, M. Piperine triggers apoptosis of human oral squamous carcinoma through cell cycle arrest and mitochondrial oxidative stress. Nutr. Cancer, 2017, 69(5), 791-799.
[] [PMID: 28426244]
Turrini, E.; Sestili, P.; Fimognari, C. Overview of the anticancer potential of the “king of spices” Piper nigrum and its main constituent piperine. Toxins (Basel), 2020, 12(12), 1-33.
[] [PMID: 33256185]
Greenshields, A.L.; Doucette, C.D.; Sutton, K.M.; Madera, L.; Annan, H.; Yaffe, P.B.; Knickle, A.F.; Dong, Z.; Hoskin, D.W. Piperine inhibits the growth and motility of triple-negative breast cancer cells. Cancer Lett., 2015, 357(1), 129-140.
[] [PMID: 25444919]
AbouAitah, K.; Stefanek, A.; Higazy, I.M.; Janczewska, M.; Swiderska-Sroda, A.; Chodara, A.; Wojnarowicz, J.; Szałaj, U.; Shahein, S.A.; Aboul-Enein, A.M.; Abou-Elella, F.; Gierlotka, S.; Ciach, T.; Lojkowski, W. Effective targeting of colon cancer cells with piperine natural anticancer prodrug using functionalized clusters of hydroxyapatite nanoparticles. Pharmaceutics, 2020, 12(1), 1-28.
[] [PMID: 31963155]
Li, H.; Wu, X.; Li, X.; Cao, X.; Li, Y.; Cao, H.; Men, Y. Multistage extraction of star anise and black pepper derivatives for antibacterial, antioxidant, and anticancer activity. Front. Chem., 2021, 9, 660138.
[] [PMID: 34055736]
Bang, J.S.; Oh, D.H.; Choi, H.M.; Sur, B.J.; Lim, S.J.; Kim, J.Y.; Yang, H.I.; Yoo, M.C.; Hahm, D.H.; Kim, K.S. Anti-inflammatory and antiarthritic effects of piperine in human interleukin 1β-stimulated fibroblast-like synoviocytes and in rat arthritis models. Arthritis Res. Ther., 2009, 11(2), R49.
[] [PMID: 19327174]
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.
Zhang, J.; Ye, K.P.; Zhang, X.; Pan, D.D.; Sun, Y.Y.; Cao, J.X. Antibacterial activity and mechanism of action of black pepper essential oil on meat-borne Escherichia coli. Front. Microbiol., 2017, 7, 2094.
[] [PMID: 28101081]
Bagheri, H.; Abdul Manap, M.Y.; Solati, Z. Antioxidant activity of Piper nigrum L. essential oil extracted by supercritical CO2 extraction and hydro-distillation. Talanta, 2014, 121, 220-228.
[] [PMID: 24607131]
Deng, Y.; Sriwiriyajan, S.; Tedasen, A.; Hiransai, P.; Graidist, P. Anti-cancer effects of Piper nigrumvia inducing multiple molecular signaling in vivo and in vitro. J. Ethnopharmacol., 2016, 188, 87-95.
[] [PMID: 27155135]
Hritcu, L.; Noumedem, J.A.; Cioanca, O.; Hancianu, M.; Postu, P.; Mihasan, M. Anxiolytic and antidepressant profile of the methanolic extract of Piper nigrum fruits in beta-amyloid (1-42) rat model of Alzheimer’s disease. Behav. Brain Funct., 2015, 11(1), 13.
[] [PMID: 25880991]
Shamkuwar, P.B.; Shahi, S.R.; Jadhav, S.T. Evaluation of antidiarrhoeal effect of Black pepper (Piper nigrum L.). Asian J. Plant Sci. Res., 2012, 2(1), 48-53.
Bukhari, I.A.; Pivac, N.; Alhumayyd, M.S.; Mahesar, A.L.; Gilani, A.H. The analgesic and anticonvulsant effects of piperine in mice. J. Physiol. Pharmacol., 2013, 64(6), 789-794.
[PMID: 24388894]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy