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Mini-Reviews in Medicinal Chemistry

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ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

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Mini-Review Article

Overview of Piperine: Bioactivities, Total Synthesis, Structural Modification, and Structure-Activity Relationships

Author(s): Shaochen Li, Min Lv* and Hui Xu*

Volume 23, Issue 8, 2023

Published on: 12 October, 2022

Page: [917 - 940] Pages: 24

DOI: 10.2174/1389557522666220726121012

Price: $65

Abstract

Natural products are an invaluable source for the discovery of drug and pesticide candidates. Piperine, a simple and pungent alkaloid, is isolated from several plants of Piperaceae. Piperine and its derivatives displayed a wide range of biological properties, such as antitumor activity, anti-inflammatory activity, antioxidant activity, neuroprotective activity, insecticidal activity, etc. In recent years, lots of works focused on the biological activities, mechanisms of action, total synthesis, and structural modifications of piperine and its derivatives have been conducted. To the best of our knowledge, however, few review articles related to the biological activities, mechanisms of action, total synthesis, and structural modifications of piperine and its derivatives have been reported to date. Therefore, this review summarizes the research advances (from 2014 to 2020) of piperine and its derivatives regarding bioactivity, mechanisms of action, total synthesis, and structural modifications. Meanwhile, the structure-activity relationships of piperine and its derivatives are also discussed.

Keywords: Piperine, Biological activity, Mechanism of action, Total synthesis, Structural modification, Structure-activity relationship.

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Graphical Abstract

[1]
Islam, M.T.; Hasan, J.; Snigdha, H.M.S.H.; Ali, E.S.; Sharifi-Rad, J.; Martorell, M.; Mubarak, M.S. Chemical profile, traditional uses, and biological activities of Piper chaba hunter: A review. J. Ethnopharmacol., 2020, 257, 112853.
[http://dx.doi.org/10.1016/j.jep.2020.112853] [PMID: 32283191]
[2]
Yadav, V.; Krishnan, A.; Vohora, D. A systematic review on Piper longum L.: Bridging traditional knowledge and pharmacological evidence for future translational research. J. Ethnopharmacol., 2020, 247, 112255.
[http://dx.doi.org/10.1016/j.jep.2019.112255] [PMID: 31568819]
[3]
Obst, K.; Lieder, B.; Reichelt, K.V.; Backes, M.; Paetz, S.; Geißler, K.; Krammer, G.; Somoza, V.; Ley, J.P.; Engel, K.H. Sensory active piperine analogues from Macropiper excelsum and their effects on intestinal nutrient uptake in Caco-2 cells. Phytochemistry, 2017, 135, 181-190.
[http://dx.doi.org/10.1016/j.phytochem.2016.12.016] [PMID: 28065397]
[4]
Muharini, R.; Liu, Z.; Lin, W.; Proksch, P. New amides from the fruits of Piper retrofractum. Tetrahedron Lett., 2015, 56(19), 2521-2525.
[http://dx.doi.org/10.1016/j.tetlet.2015.03.116]
[5]
Abdubakiev, S.; Li, H.; Lu, X.; Li, J.; Aisa, H.A. N-Alkylamides from Piper longum L. and their stimulative effects on the melanin content and tyrosinase activity in B16 melanoma cells. Nat. Prod. Res., 2020, 34(17), 2510-2513.
[http://dx.doi.org/10.1080/14786419.2018.1539982] [PMID: 30623685]
[6]
Tharmalingam, N.; Kim, S.H.; Park, M.; Woo, H.J.; Kim, H.W.; Yang, J.Y.; Rhee, K.J.; Kim, J.B. Inhibitory effect of piperine on Helicobacter pylori growth and adhesion to gastric adenocarcinoma cells. Infect. Agent. Cancer, 2014, 9(1), 43.
[http://dx.doi.org/10.1186/1750-9378-9-43] [PMID: 25584066]
[7]
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.
[http://dx.doi.org/10.1016/j.canlet.2014.11.017] [PMID: 25444919]
[8]
Lei, J.; Burgess, E.J.; Richardson, A.T.; Hawkins, B.C.; Baird, S.K.; Smallfield, B.M.; van Klink, J.W.; Perry, N.B. Cytotoxic amides from fruits of Kawakawa, Macropiper excelsum. Planta Med., 2015, 81(12-13), 1163-1168.
[http://dx.doi.org/10.1055/s-0035-1546106] [PMID: 26039266]
[9]
Pachauri, M.; Gupta, E.D.; Ghosh, P.C. Piperine loaded PEG-PLGA nanoparticles: Preparation, characterization and targeted delivery for adjuvant breast cancer chemotherapy. J. Drug Deliv. Sci. Technol., 2015, 29, 269-282.
[http://dx.doi.org/10.1016/j.jddst.2015.08.009]
[10]
Patial, V.S.M.; Sharma, S.; Pratap, K.; Singh, D.; Padwad, Y.S. Synergistic effect of curcumin and piperine in suppression of DENA-induced hepatocellular carcinoma in rats. Environ. Toxicol. Pharmacol., 2015, 40(2), 445-452.
[http://dx.doi.org/10.1016/j.etap.2015.07.012] [PMID: 26278679]
[11]
Zhang, J.; Zhu, X.; Li, H.; Li, B.; Sun, L.; Xie, T.; Zhu, T.; Zhou, H.; Ye, Z. Piperine inhibits proliferation of human osteosarcoma cells via G2/M phase arrest and metastasis by suppressing MMP-2/-9 expression. Int. Immunopharmacol., 2015, 24(1), 50-58.
[http://dx.doi.org/10.1016/j.intimp.2014.11.012] [PMID: 25479727]
[12]
Jain, S.; Meka, S.R.K.; Chatterjee, K. Engineering a piperine eluting nanofibrous patch for cancer treatment. ACS Biomater. Sci. Eng., 2016, 2(8), 1376-1385.
[http://dx.doi.org/10.1021/acsbiomaterials.6b00297] [PMID: 33434991]
[13]
Pal, M.K.; Jaiswar, S.P.; Srivastav, A.K.; Goyal, S.; Dwivedi, A.; Verma, A.; Singh, J.; Pathak, A.K.; Sankhwar, P.L.; Ray, R.S. Synergistic effect of piperine and paclitaxel on cell fate via cyt-c, Bax/Bcl-2-caspase-3 pathway in ovarian adenocarcinomas SKOV-3 cells. Eur. J. Pharmacol., 2016, 791, 751-762.
[http://dx.doi.org/10.1016/j.ejphar.2016.10.019] [PMID: 27756602]
[14]
Raza, K.; Kumar, D.; Kiran, C.; Kumar, M.; Guru, S.K.; Kumar, P.; Arora, S.; Sharma, G.; Bhushan, S.; Katare, O.P. Conjugation of docetaxel with multiwalled carbon nanotubes and codelivery with piperine: Implications on pharmacokinetic profile and anticancer activity. Mol. Pharm., 2016, 13(7), 2423-2432.
[http://dx.doi.org/10.1021/acs.molpharmaceut.6b00183] [PMID: 27182646]
[15]
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.
[http://dx.doi.org/10.1080/01635581.2017.1310260] [PMID: 28426244]
[16]
Talib, W.H. Regressions of breast carcinoma syngraft following treatment with piperine in combination with thymoquinone. Sci. Pharm., 2017, 85(3), 27.
[http://dx.doi.org/10.3390/scipharm85030027] [PMID: 28671634]
[17]
Zeng, Y.; Yang, Y. Piperine depresses the migration progression via downregulating the Akt/mTOR/MMP 9 signaling pathway in DU145 cells. Mol. Med. Rep., 2018, 17(5), 6363-6370.
[http://dx.doi.org/10.3892/mmr.2018.8653] [PMID: 29488612]
[18]
Li, H.; Krstin, S.; Wang, S.; Wink, M. Capsaicin and piperine can overcome multidrug resistance in cancer cells to doxorubicin. Molecules, 2018, 23(3), 557.
[http://dx.doi.org/10.3390/molecules23030557] [PMID: 29498663]
[19]
George, K.; Thomas, N.S.; Malathi, R. Piperine blocks voltage gated K+ current and inhibits proliferation in androgen sensitive and insensitive human prostate cancer cell lines. Arch. Biochem. Biophys., 2019, 667, 36-48.
[http://dx.doi.org/10.1016/j.abb.2019.04.007] [PMID: 31047869]
[20]
Grinevicius, V.M.A.S.; Andrade, K.S.; Mota, N.S.R.S.; Bretanha, L.C.; Felipe, K.B.; Ferreira, S.R.S.; Pedrosa, R.C. CDK2 and Bcl-xL inhibitory mechanisms by docking simulations and anti-tumor activity from piperine enriched supercritical extract. Food Chem. Toxicol., 2019, 132, 110644.
[http://dx.doi.org/10.1016/j.fct.2019.110644] [PMID: 31252023]
[21]
Shankar, S.; Faheem, M.M.; Nayak, D.; Wani, N.A.; Farooq, S.; Koul, S.; Goswami, A.; Rai, R. Cyclodipeptide c(Orn-Pro) conjugate with 4-ethylpiperic acid abrogates cancer cell metastasis through modulating MDM2. Bioconjug. Chem., 2018, 29(1), 164-175.
[http://dx.doi.org/10.1021/acs.bioconjchem.7b00670] [PMID: 29216716]
[22]
Nandakumar, N.; Muthuraman, S.; Gopinath, P.; Nithya, P.; Gopas, J.; Kumar, R.S. Synthesis of coumaperine derivatives: Their NF-κB inhibitory effect, inhibition of cell migration and their cytotoxic activity. Eur. J. Med. Chem., 2017, 125, 1076-1087.
[http://dx.doi.org/10.1016/j.ejmech.2016.10.047] [PMID: 27810594]
[23]
Ali, Y.; Alam, M.S.; Hamid, H.; Husain, A.; Bano, S.; Dhulap, A.; Kharbanda, C.; Nazreen, S.; Haider, S. Design, synthesis and biological evaluation of piperic acid triazolyl derivatives as potent anti-inflammatory agents. Eur. J. Med. Chem., 2015, 92, 490-500.
[http://dx.doi.org/10.1016/j.ejmech.2015.01.001] [PMID: 25596479]
[24]
Dong, Y.; Huihui, Z.; Li, C. Piperine inhibit inflammation, alveolar bone loss and collagen fibers breakdown in a rat periodontitis model. J. Periodontal Res., 2015, 50(6), 758-765.
[http://dx.doi.org/10.1111/jre.12262] [PMID: 25736698]
[25]
Doucette, C.D.; Greenshields, A.L.; Liwski, R.S.; Hoskin, D.W. Piperine blocks interleukin-2-driven cell cycle progression in CTLL-2 T lymphocytes by inhibiting multiple signal transduction pathways. Toxicol. Lett., 2015, 234(1), 1-12.
[http://dx.doi.org/10.1016/j.toxlet.2015.01.020] [PMID: 25655587]
[26]
Doucette, C.D.; Rodgers, G.; Liwski, R.S.; Hoskin, D.W. Piperine from black pepper inhibits activation-induced proliferation and effector function of T lymphocytes. J. Cell. Biochem., 2015, 116(11), 2577-2588.
[http://dx.doi.org/10.1002/jcb.25202] [PMID: 25900378]
[27]
Gupta, R.A.; Motiwala, M.N.; Dumore, N.G.; Danao, K.R.; Ganjare, A.B. Effect of piperine on inhibition of FFA induced TLR4 mediated inflammation and amelioration of acetic acid induced ulcerative colitis in mice. J. Ethnopharmacol., 2015, 164, 239-246.
[http://dx.doi.org/10.1016/j.jep.2015.01.039] [PMID: 25683300]
[28]
Hou, X.F.; Pan, H.; Xu, L.H.; Zha, Q.B.; He, X.H.; Ouyang, D.Y. Piperine suppresses the expression of CXCL8 in lipopolysaccharide-activated SW480 and HT-29 cells via downregulating the mitogen-activated protein kinase pathways. Inflammation, 2015, 38(3), 1093-1102.
[http://dx.doi.org/10.1007/s10753-014-0075-z] [PMID: 25471891]
[29]
Li, Q.; Zhai, W.; Jiang, Q.; Huang, R.; Liu, L.; Dai, J.; Gong, W.; Du, S.; Wu, Q. Curcumin-piperine mixtures in self-microemulsifying drug delivery system for ulcerative colitis therapy. Int. J. Pharm., 2015, 490(1-2), 22-31.
[http://dx.doi.org/10.1016/j.ijpharm.2015.05.008] [PMID: 25957703]
[30]
Lu, Y.; Liu, J.; Li, H.; Gu, L. Piperine ameliorates lipopolysaccharide-induced acute lung injury via modulating NF-κb signaling pathways. Inflammation, 2016, 39(1), 303-308.
[http://dx.doi.org/10.1007/s10753-015-0250-x] [PMID: 26410851]
[31]
Jadhav, S.A.; Prabhavalkar, K. Anti-inflammatory activity of trans-cinnamaldehyde and piperine combination against carrageenan induced paw edema. Int. J. Pharm. Sci. Res., 2015, 6(12), 5188-5192.
[http://dx.doi.org/10.13040/ijpsr.0975-8232.6(12).5188-92]
[32]
Soutar, D.A.; Doucette, C.D.; Liwski, R.S.; Hoskin, D.W. Piperine, a pungent alkaloid from black pepper, inhibits B lymphocyte activation and effector functions. Phytother. Res., 2017, 31(3), 466-474.
[http://dx.doi.org/10.1002/ptr.5772] [PMID: 28102026]
[33]
Wang-Sheng, C.; Jie, A.; Jian-Jun, L.; Lan, H.; Zeng-Bao, X.; Chang-Qing, L. Piperine attenuates lipopolysaccharide (LPS)-induced inflammatory responses in BV2 microglia. Int. Immunopharmacol., 2017, 42, 44-48.
[http://dx.doi.org/10.1016/j.intimp.2016.11.001] [PMID: 27875748]
[34]
Peng, X.; Yang, T.; Liu, G.; Liu, H.; Peng, Y.; He, L. Piperine ameliorated lupus nephritis by targeting AMPK-mediated activation of NLRP3 inflammasome. Int. Immunopharmacol., 2018, 65, 448-457.
[http://dx.doi.org/10.1016/j.intimp.2018.10.025] [PMID: 30388519]
[35]
Pei, H.; Xue, L.; Tang, M.; Tang, H.; Kuang, S.; Wang, L.; Ma, X.; Cai, X.; Li, Y.; Zhao, M.; Peng, A.; Ye, H.; Chen, L. Alkaloids from black pepper (Piper nigrum L.) exhibit anti-inflammatory activity in murine macrophages by inhibiting activation of NF-κB pathway. J. Agric. Food Chem., 2020, 68(8), 2406-2417.
[http://dx.doi.org/10.1021/acs.jafc.9b07754] [PMID: 32031370]
[36]
Wang, H.; Liu, J.; Gao, G.; Wu, X.; Wang, X.; Yang, H. Protection effect of piperine and piperlonguminine from Piper longum L. alkaloids against rotenone-induced neuronal injury. Brain Res., 2016, 1639, 214-227.
[http://dx.doi.org/10.1016/j.brainres.2015.07.029] [PMID: 26232071]
[37]
Singh, S.; Kumar, P. Neuroprotective potential of curcumin in combination with piperine against 6-hydroxy dopamine induced motor deficit and neurochemical alterations in rats. Inflammopharmacology, 2017, 25(1), 69-79.
[http://dx.doi.org/10.1007/s10787-016-0297-9] [PMID: 27853890]
[38]
Guo, J.; Cui, Y.; Liu, Q.; Yang, Y.; Li, Y.; Weng, L.; Tang, B.; Jin, P.; Li, X.J.; Yang, S.; Li, S. Piperine ameliorates SCA17 neuropathology by reducing ER stress. Mol. Neurodegener., 2018, 13(1), 4.
[http://dx.doi.org/10.1186/s13024-018-0236-x] [PMID: 29378605]
[39]
Wang, L.; Cai, X.; Shi, M.; Xue, L.; Kuang, S.; Xu, R.; Qi, W.; Li, Y.; Ma, X.; Zhang, R.; Hong, F.; Ye, H.; Chen, L. Identification and optimization of piperine analogues as neuroprotective agents for the treatment of Parkinson’s disease via the activation of Nrf2/keap1 pathway. Eur. J. Med. Chem., 2020, 199, 112385.
[http://dx.doi.org/10.1016/j.ejmech.2020.112385] [PMID: 32402936]
[40]
Tu, Y.; Zhong, Y.; Du, H.; Luo, W.; Wen, Y.; Li, Q.; Zhu, C.; Li, Y. Anticholinesterases and antioxidant alkamides from Piper nigrum fruits. Nat. Prod. Res., 2016, 30(17), 1945-1949.
[http://dx.doi.org/10.1080/14786419.2015.1089243] [PMID: 26407107]
[41]
Whitehouse, S.; Chen, P.L.; Greenshields, A.L.; Nightingale, M.; Hoskin, D.W.; Bedard, K. Resveratrol, piperine and apigenin differ in their NADPH-oxidase inhibitory and reactive oxygen species-scavenging properties. Phytomedicine, 2016, 23(12), 1494-1503.
[http://dx.doi.org/10.1016/j.phymed.2016.08.011] [PMID: 27765370]
[42]
Dhivya, V.; Priya, L.B.; Chirayil, H.T.; Sathiskumar, S.; Huang, C.Y.; Padma, V.V. Piperine modulates isoproterenol induced myocardial ischemia through antioxidant and anti-dyslipidemic effect in male Wistar rats. Biomed. Pharmacother., 2017, 87, 705-713.
[http://dx.doi.org/10.1016/j.biopha.2017.01.002] [PMID: 28088738]
[43]
Qin, B.; Yang, K.; Cao, R. Synthesis and antioxidative activity of piperine derivatives containing phenolic hydroxyl. J. Chem., 2020, 2020, 1-9.
[http://dx.doi.org/10.1155/2020/2786359]
[44]
Muthuraman, S.; Sinha, S.; Vasavi, C.S.; Waidha, K.M.; Basu, B.; Munussami, P.; Balamurali, M.M.; Doble, M.; Saravana Kumar, R. Design, synthesis and identification of novel coumaperine derivatives for inhibition of human 5-LOX: Antioxidant, pseudoperoxidase and docking studies. Bioorg. Med. Chem., 2019, 27(4), 604-619.
[http://dx.doi.org/10.1016/j.bmc.2018.12.043] [PMID: 30638966]
[45]
Elnaggar, Y.S.; Etman, S.M.; Abdelmonsif, D.A.; Abdallah, O.Y. Novel piperine-loaded Tween-integrated monoolein cubosomes as brain-targeted oral nanomedicine in Alzheimer’s disease: Pharmaceutical, biological, and toxicological studies. Int. J. Nanomed, 2015, 10, 5459-5473.
[http://dx.doi.org/10.2147/IJN.S87336] [PMID: 26346130]
[46]
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.
[http://dx.doi.org/10.1016/j.jnutbio.2019.05.009] [PMID: 31207354]
[47]
Yang, R.; Lv, M.; Xu, H. Synthesis of piperine analogs containing isoxazoline/pyrazoline scaffold and their pesticidal bioactivities. J. Agric. Food Chem., 2018, 66(43), 11254-11264.
[http://dx.doi.org/10.1021/acs.jafc.8b03690] [PMID: 30295024]
[48]
Huang, X.; Zhang, B.; Xu, H. Synthesis of some monosaccharide-related ester derivatives as insecticidal and acaricidal agents. Bioorg. Med. Chem. Lett., 2017, 27(18), 4336-4340.
[http://dx.doi.org/10.1016/j.bmcl.2017.08.031] [PMID: 28844385]
[49]
Li, Y.; Li, M.; Wu, S.; Tian, Y. Combination of curcumin and piperine prevents formation of gallstones in C57BL6 mice fed on lithogenic diet: Whether NPC1L1/SREBP2 participates in this process? Lipids Health Dis., 2015, 14(1), 100.
[http://dx.doi.org/10.1186/s12944-015-0106-2] [PMID: 26335572]
[50]
Song, X.Y.; Xu, S.; Hu, J.F.; Tang, J.; Chu, S.F.; Liu, H.; Han, N.; Li, J.W.; Zhang, D.M.; Li, Y.T.; Chen, N.H. Piperine prevents cholesterol gallstones formation in mice. Eur. J. Pharmacol., 2015, 751, 112-117.
[http://dx.doi.org/10.1016/j.ejphar.2015.01.038] [PMID: 25645812]
[51]
Wang, D.; Zhang, L.; Huang, J.; Himabindu, K.; Tewari, D. Horbańczuk, J.O.; Xu, S.; Chen, Z.; Atanasov, A.G. Cardiovascular protective effect of black pepper (Piper nigrum L.) and its major bioactive constituent piperine. Trends Food Sci. Technol., 2021, 117, 34-45.
[http://dx.doi.org/10.1016/j.tifs.2020.11.024]
[52]
Khameneh, B.; Iranshahy, M.; Ghandadi, M.; Ghoochi Atashbeyk, D.; Fazly Bazzaz, B.S.; Iranshahi, M. Investigation of the antibacterial activity and efflux pump inhibitory effect of co-loaded piperine and gentamicin nanoliposomes in methicillin-resistant Staphylococcus aureus. Drug Dev. Ind. Pharm., 2015, 41(6), 989-994.
[http://dx.doi.org/10.3109/03639045.2014.920025] [PMID: 24842547]
[53]
Liang, Y.D.; Bai, W.J.; Li, C.G.; Xu, L.H.; Wei, H.X.; Pan, H.; He, X.H.; Ouyang, D.Y. Piperine suppresses pyroptosis and interleukin-1β release upon ATP triggering and bacterial infection. Front. Pharmacol., 2016, 7, 390.
[http://dx.doi.org/10.3389/fphar.2016.00390] [PMID: 27812336]
[54]
Moon, Y.S.; Choi, W.S.; Park, E.S.; Bae, I.K.; Choi, S.D.; Paek, O.; Kim, S.H.; Chun, H.S.; Lee, S.E. Antifungal and antiaflatoxigenic methylenedioxy-containing compounds and piperine-like synthetic compounds. Toxins (Basel), 2016, 8(8), 240.
[http://dx.doi.org/10.3390/toxins8080240] [PMID: 27537912]
[55]
Amperayani, K.R.; Kumar, K.N.; Parimi, U.D. Synthesis and in vitro and in silico antimicrobial studies of novel piperine–pyridine analogs. Res. Chem. Intermed., 2018, 44(5), 3549-3564.
[http://dx.doi.org/10.1007/s11164-018-3324-1]
[56]
Kumar, K.N.; Amperayani, K.R.; Sankar Ummdi, V.R.; Parimi, U.D. Synthesis and antimicrobial activity of piperine analogues containing 1,2,4-triazole ring. Asian J. Chem., 2019, 31(5), 1077-1080.
[http://dx.doi.org/10.14233/ajchem.2019.21876]
[57]
Philipova, I.; Valcheva, V.; Mihaylova, R.; Mateeva, M.; Doytchinova, I.; Stavrakov, G. Synthetic piperine amide analogs with antimycobacterial activity. Chem. Biol. Drug Des., 2018, 91(3), 763-768.
[http://dx.doi.org/10.1111/cbdd.13140] [PMID: 29130602]
[58]
Arcaro, C.A.; Gutierres, V.O.; Assis, R.P.; Moreira, T.F.; Costa, P.I.; Baviera, A.M.; Brunetti, I.L. 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]
[59]
Kharbanda, C.; Alam, M.S.; Hamid, H.; Javed, K.; Bano, S.; Ali, Y.; Dhulap, A.; Alam, P.; Pasha, M.A. Novel piperine derivatives with antidiabetic effect as PPAR-γ agonists. Chem. Biol. Drug Des., 2016, 88(3), 354-362.
[http://dx.doi.org/10.1111/cbdd.12760] [PMID: 27037532]
[60]
Samra, Y.A.; Said, H.S.; Elsherbiny, N.M.; Liou, G.I.; El-Shishtawy, M.M.; Eissa, L.A. Cepharanthine and Piperine ameliorate diabetic nephropathy in rats: Role of NF-κB and NLRP3 inflammasome. Life Sci., 2016, 157, 187-199.
[http://dx.doi.org/10.1016/j.lfs.2016.06.002] [PMID: 27266851]
[61]
Singh, S.; Jamwal, S.; Kumar, P. Piperine enhances the protective effect of curcumin against 3-NP induced neurotoxicity: Possible neurotransmitters modulation mechanism. Neurochem. Res., 2015, 40(8), 1758-1766.
[http://dx.doi.org/10.1007/s11064-015-1658-2] [PMID: 26160706]
[62]
Jangra, A.; Kwatra, M.; Singh, T.; Pant, R.; Kushwah, P.; Sharma, Y.; Saroha, B.; Datusalia, A.K.; Bezbaruah, B.K. Piperine augments the protective effect of curcumin against lipopolysaccharide-induced neurobehavioral and neurochemical deficits in mice. Inflammation, 2016, 39(3), 1025-1038.
[http://dx.doi.org/10.1007/s10753-016-0332-4] [PMID: 26970969]
[63]
Singh, S.; Kumar, P. Neuroprotective activity of curcumin in combination with piperine against quinolinic acid induced neurodegeneration in rats. Pharmacology, 2016, 97(3-4), 151-160.
[http://dx.doi.org/10.1159/000443896] [PMID: 26828892]
[64]
Dubey, R.K.; Leeners, B.; Imthurn, B.; Merki-Feld, G.S.; Rosselli, M. Piperine decreases binding of drugs to human plasma and increases uptake by brain microvascular endothelial cells. Phytother. Res., 2017, 31(12), 1868-1874.
[http://dx.doi.org/10.1002/ptr.5929] [PMID: 28948673]
[65]
Kaur, H.; He, B.; Zhang, C.; Rodriguez, E.; Hage, D.S.; Moreau, R. Piperine potentiates curcumin-mediated repression of mTORC1 signaling in human intestinal epithelial cells: Implications for the inhibition of protein synthesis and TNFα signaling. J. Nutr. Biochem., 2018, 57, 276-286.
[http://dx.doi.org/10.1016/j.jnutbio.2018.04.010] [PMID: 29800814]
[66]
Bi, X.; Yuan, Z.; Qu, B.; Zhou, H.; Liu, Z.; Xie, Y. Piperine enhances the bioavailability of silybin via inhibition of efflux transporters BCRP and MRP2. Phytomedicine, 2019, 54, 98-108.
[http://dx.doi.org/10.1016/j.phymed.2018.09.217] [PMID: 30668388]
[67]
Ren, T.; Hu, M.; Cheng, Y.; Shek, T.L.; Xiao, M.; Ho, N.J.; Zhang, C.; Leung, S.S.Y.; Zuo, Z. Piperine-loaded nanoparticles with enhanced dissolution and oral bioavailability for epilepsy control. Eur. J. Pharm. Sci., 2019, 137, 104988.
[http://dx.doi.org/10.1016/j.ejps.2019.104988] [PMID: 31291598]
[68]
Qu, H.; Lv, M.; Xu, H. Piperine: Bioactivities and structural modifications. Mini Rev. Med. Chem., 2015, 15(2), 145-156.
[http://dx.doi.org/10.2174/1389557515666150101100509] [PMID: 25553428]
[69]
Haq, I.U.; Imran, M.; Nadeem, M.; Tufail, T.; Gondal, T.A.; Mubarak, M.S. Piperine: A review of its biological effects. Phytother. Res., 2021, 35(2), 680-700.
[http://dx.doi.org/10.1002/ptr.6855] [PMID: 32929825]
[70]
Yun, Y.S.; Noda, S.; Takahashi, S.; Takahashi, Y.; Inoue, H. Piperine-like alkamides from Piper nigrum induce BDNF promoter and promote neurite outgrowth in Neuro-2a cells. J. Nat. Med., 2018, 72(1), 238-245.
[http://dx.doi.org/10.1007/s11418-017-1140-3] [PMID: 29063362]
[71]
Mair, C.E.; Liu, R.; Atanasov, A.G.; Wimmer, L.; Nemetz-Fiedler, D.; Sider, N.; Heiss, E.H.; Mihovilovic, M.D.; Dirsch, V.M.; Rollinger, J.M. Piperine congeners as inhibitors of vascular smooth muscle cell proliferation. Planta Med., 2015, 81(12-13), 1065-1074.
[http://dx.doi.org/10.1055/s-0035-1546165] [PMID: 26132851]
[72]
Ahmed, A.A.; Mahmoud, A.A.; Ali, E.T.; Tzakou, O.; Couladis, M.; Mabry, T.J.; Gáti, T.; Tóth, G. Two highly oxygenated eudesmanes and 10 lignans from Achillea holosericea. Phytochemistry, 2002, 59(8), 851-856.
[http://dx.doi.org/10.1016/S0031-9422(01)00442-3] [PMID: 11937165]
[73]
Greger, H.; Hofer, O. New unsymmetrically substituted tetrahydrofurofuran lignans from Artemisia absinthium. Tetrahedron, 1980, 36(24), 3551-3558.
[http://dx.doi.org/10.1016/0040-4020(80)88051-3]
[74]
Solís, P.N.; Olmedo, D.; Nakamura, N.; Calderón, A.I.; Hattori, M.; Gupta, M.P. A new larvicidal lignan from Piper fimbriulatum. Pharm. Biol., 2005, 43(4), 378-381.
[http://dx.doi.org/10.1080/13880200590951865] [PMID: 28925841]
[75]
Matsuda, H.; Ninomiya, K.; Morikawa, T.; Yasuda, D.; Yamaguchi, I.; Yoshikawa, M. Hepatoprotective amide constituents from the fruit of Piper chaba: Structural requirements, mode of action, and new amides. Bioorg. Med. Chem., 2009, 17(20), 7313-7323.
[http://dx.doi.org/10.1016/j.bmc.2009.08.050] [PMID: 19775895]
[76]
Kapoor, I.P.; Singh, B.; Singh, G.; De Heluani, C.S.; De Lampasona, M.P.; Catalan, C.A. Chemistry and in vitro antioxidant activity of volatile oil and oleoresins of black pepper (Piper nigrum). J. Agric. Food Chem., 2009, 57(12), 5358-5364.
[http://dx.doi.org/10.1021/jf900642x] [PMID: 19456163]
[77]
Saadali, B.; Boriky, D.; Blaghen, M.; Vanhaelen, M.; Talbi, M. Alkamides from Artemisia dracunculus. Phytochemistry, 2001, 58(7), 1083-1086.
[http://dx.doi.org/10.1016/S0031-9422(01)00347-8] [PMID: 11730872]
[78]
Kumar, A.; Sharma, N. Comparative efficacy of piperine and curcumin in deltamethrin induced splenic apoptosis and altered immune functions. Pestic. Biochem. Physiol., 2015, 119, 16-27.
[http://dx.doi.org/10.1016/j.pestbp.2015.03.003] [PMID: 25868812]
[79]
Mihăilă B.; Dinică R.M.; Tatu, A.L.; Buzia, O.D. New insights in vitiligo treatments using bioactive compounds from Piper nigrum. Exp. Ther. Med., 2019, 17(2), 1039-1044.
[http://dx.doi.org/10.3892/etm.2018.6977] [PMID: 30679971]
[80]
Wani, N.A.; Singh, S.; Farooq, S.; Shankar, S.; Koul, S.; Khan, I.A.; Rai, R. Amino acid amides of piperic acid (PA) and 4-ethylpiperic acid (EPA) as NorA efflux pump inhibitors of Staphylococcus aureus. Bioorg. Med. Chem. Lett., 2016, 26(17), 4174-4178.
[http://dx.doi.org/10.1016/j.bmcl.2016.07.062] [PMID: 27503686]
[81]
Sun, Q.; Xie, L.; Song, J.; Li, X. Evodiamine: A review of its pharmacology, toxicity, pharmacokinetics and preparation researches. J. Ethnopharmacol., 2020, 262, 113164.
[http://dx.doi.org/10.1016/j.jep.2020.113164] [PMID: 32738391]
[82]
Caceres, I.; El Khoury, R.; Bailly, S.; Oswald, I.P.; Puel, O.; Bailly, J.D. Piperine inhibits aflatoxin B1 production in Aspergillus flavus by modulating fungal oxidative stress response. Fungal Genet. Biol., 2017, 107, 77-85.
[http://dx.doi.org/10.1016/j.fgb.2017.08.005] [PMID: 28830793]
[83]
Tantawy, A.H.; Farag, S.M.; Hegazy, L.; Jiang, H.; Wang, M.Q. The larvicidal activity of natural inspired piperine-based dienehydrazides against Culex pipiens. Bioorg. Chem., 2020, 94, 103464.
[http://dx.doi.org/10.1016/j.bioorg.2019.103464] [PMID: 31836185]
[84]
Maeda, A.; Shirao, T.; Shirasaya, D.; Yoshioka, Y.; Yamashita, Y.; Akagawa, M.; Ashida, H. Piperine promotes glucose uptake through ROS-dependent activation of the CAMKK/AMPK signaling pathway in skeletal muscle. Mol. Nutr. Food Res., 2018, 62(11), e1800086.
[http://dx.doi.org/10.1002/mnfr.201800086] [PMID: 29683271]
[85]
Park, U.H.; Hwang, J.T.; Youn, H.; Kim, E.J.; Um, S.J. Piperine inhibits adipocyte differentiation via dynamic regulation of histone modifications. Phytother. Res., 2019, 33(9), 2429-2439.
[http://dx.doi.org/10.1002/ptr.6434] [PMID: 31359554]
[86]
Wang, L.; Palme, V.; Rotter, S.; Schilcher, N.; Cukaj, M.; Wang, D.; Ladurner, A.; Heiss, E.H.; Stangl, H.; Dirsch, V.M.; Atanasov, A.G. Piperine inhibits ABCA1 degradation and promotes cholesterol efflux from THP-1-derived macrophages. Mol. Nutr. Food Res., 2017, 61(4), 1500960.
[http://dx.doi.org/10.1002/mnfr.201500960] [PMID: 27862930]
[87]
Booranasubkajorn, S.; Huabprasert, S.; Wattanarangsan, J.; Chotitham, P.; Jutasompakorn, P.; Laohapand, T.; Akarasereenont, P.; Tripatara, P. Vasculoprotective and vasodilatation effects of herbal formula (Sahatsatara) and piperine in spontaneously hypertensive rats. Phytomedicine, 2017, 24, 148-156.
[http://dx.doi.org/10.1016/j.phymed.2016.11.013] [PMID: 28160856]
[88]
Kim, J.; Lee, K.P.; Lee, D.W.; Lim, K. Piperine enhances carbohydrate/fat metabolism in skeletal muscle during acute exercise in mice. Nutr. Metab. (Lond.), 2017, 14(1), 43.
[http://dx.doi.org/10.1186/s12986-017-0194-2] [PMID: 28680454]
[89]
Shamsi, S.; Tran, H.; Tan, R.S.; Tan, Z.J.; Lim, L.Y. Curcumin, piperine, and capsaicin: A comparative study of spice-mediated inhibition of human cytochrome P450 isozyme activities. Drug Metab. Dispos., 2017, 45(1), 49-55.
[http://dx.doi.org/10.1124/dmd.116.073213] [PMID: 27821437]
[90]
Zhao, Y.; Liu, J.; Hao, W.; He, Z.; Zhu, H.; Liang, N.; Ma, K.Y.; He, W.S.; Yang, Y.; Chen, Z.Y. Plasma cholesterol-lowering activity of piperine is mediated by inhibition on cholesterol absorption via down-regulation of intestinal ACAT2 and MTP. J. Funct. Foods, 2018, 49, 465-471.
[http://dx.doi.org/10.1016/j.jff.2018.09.014]
[91]
Kim, N.; Nam, M.; Kang, M.S.; Lee, J.O.; Lee, Y.W.; Hwang, G.S.; Kim, H.S. Piperine regulates UCP1 through the AMPK pathway by generating intracellular lactate production in muscle cells. Sci. Rep., 2017, 7(1), 41066.
[http://dx.doi.org/10.1038/srep41066] [PMID: 28117414]
[92]
Teskey, C.J.; Adler, P.; Gonçalves, C.R.; Maulide, N. Chemoselective αβ-dehydrogenation of saturated amides. Angew. Chem. Int. Ed. Engl., 2019, 58(2), 447-451.
[http://dx.doi.org/10.1002/anie.201808794] [PMID: 30332524]
[93]
Pan, G.F.; Zhang, X.L.; Zhu, X.Q.; Guo, R.L.; Wang, Y.Q. Synthesis of (E,E)-dienones and (E,E)-dienals via palladium-catalyzed γδ-dehydrogenation of enones and enals. iScience, 2019, 20, 229-236.
[http://dx.doi.org/10.1016/j.isci.2019.09.027] [PMID: 31590075]
[94]
Bauer, A.; Nam, J.H.; Maulide, N. A short, efficient, and stereoselective synthesis of piperine and its analogues. Synlett, 2019, 30(4), 413-416.
[http://dx.doi.org/10.1055/s-0037-1611652]
[95]
Takao, K.; Miyashiro, T.; Sugita, Y. Synthesis and biological evaluation of piperic acid amides as free radical scavengers and α-glucosidase inhibitors. Chem. Pharm. Bull. (Tokyo), 2015, 63(5), 326-333.
[http://dx.doi.org/10.1248/cpb.c14-00874] [PMID: 25948326]
[96]
Chavarria, D.; Cagide, F.; Pinto, M.; Gomes, L.R.; Low, J.N.; Borges, F. Development of piperic acid-based monoamine oxidase inhibitors: Synthesis, structural characterization and biological evaluation. J. Mol. Struct., 2019, 1182, 298-307.
[http://dx.doi.org/10.1016/j.molstruc.2019.01.060]
[97]
Schöffmann, A.; Wimmer, L.; Goldmann, D.; Khom, S.; Hintersteiner, J.; Baburin, I.; Schwarz, T.; Hintersteininger, M.; Pakfeifer, P.; Oufir, M.; Hamburger, M.; Erker, T.; Ecker, G.F.; Mihovilovic, M.D.; Hering, S. Efficient modulation of γ-aminobutyric acid type A receptors by piperine derivatives. J. Med. Chem., 2014, 57(13), 5602-5619.
[http://dx.doi.org/10.1021/jm5002277] [PMID: 24905252]
[98]
Eigenmann, D.E.; Dürig, C.; Jähne, E.A.; Smieško, M.; Culot, M.; Gosselet, F.; Cecchelli, R.; Helms, H.C.C.; Brodin, B.; Wimmer, L.; Mihovilovic, M.D.; Hamburger, M.; Oufir, M. In vitro blood-brain barrier permeability predictions for GABAA receptor modulating piperine analogs. Eur. J. Pharm. Biopharm., 2016, 103, 118-126.
[http://dx.doi.org/10.1016/j.ejpb.2016.03.029] [PMID: 27018328]
[99]
Fernandes, I.A.; de Almeida, L.; Ferreira, P.E.; Marques, M.J.; Rocha, R.P.; Coelho, L.F.; Carvalho, D.T.; Viegas, C., Jr Synthesis and biological evaluation of novel piperidine-benzodioxole derivatives designed as potential leishmanicidal drug candidates. Bioorg. Med. Chem. Lett., 2015, 25(16), 3346-3349.
[http://dx.doi.org/10.1016/j.bmcl.2015.05.068] [PMID: 26094119]
[100]
Wimmer, L.; Schönbauer, D.; Pakfeifer, P.; Schöffmann, A.; Khom, S.; Hering, S.; Mihovilovic, M.D. Developing piperine towards TRPV1 and GABAA receptor ligands-synthesis of piperine analogs via Heck-coupling of conjugated dienes. Org. Biomol. Chem., 2015, 13(4), 990-994.
[http://dx.doi.org/10.1039/C4OB02242D] [PMID: 25438036]

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