Drug-Piperaceae Herb Interaction Potency Through Analgesic, Anxiolytic, and AntiInflammatory Activity Studies
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Abstract
Integrative therapy by combining conventional with herbal medicines is one of the choices for the community. However, there are opportunities for potential drug-herb interactions. Piperine, the primary alkaloid in the Piperaceae family, has been shown to change the pharmacokinetic profile of drugs and influence drug pharmacodynamics. This study aimed to determine the potential interactions between the combination of Piperaceae herb extract and conventional drugs based on their pharmacological activity in vivo. Black and Javanese long pepper extracts were prepared using the maceration method in ethanol. Then, the piperine level was determined using the TLC densitometric method. Potential interactions were investigated through in vivo analgesic, anxiolytic, and anti-inflammatory activity studies. Piperine content in black and Javanese long pepper extract was 20.46% and 15.65%, respectively. Conventional drugs consumed with piperine or Piperaceae herbal extracts showed an increase in the latency time of mice on a hot-cold plate but a decrease in mice's survival time on the rotarod and oedema volume compared to single drug administration at various times. All combined treatments also enhance the percentage of analgesic (21.73% to 25.60%), anxiolytic (65% to ≥80%), and inflammation inhibitory (14.81% to ≥51.85%) activities of drugs. It concluded that piperine in black pepper or Javanese long pepper extracts has the potency to interact with drugs, especially with diclofenac sodium, alprazolam, and dexamethasone, based on the enhancement of their activity. Thus, further research is needed to determine its toxicity and pharmacokinetic profile to ensure the safety of these drug interactions.
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Borse SP, Singh DP, Nivsarkar M. Understanding the relevance of herb–drug interaction studies with special focus on interplays: a prerequisite for integrative medicine. Porto Biomed J. 2019;4(2):e15.
doi:10.1016/j.pbj.0000000000000015
Pane MH, Rahman AO, Ayudia EI. Overview of the Use of Herbal Medicines in Indonesian Society and Their Interactions with Conventional Medicines in 2020. J Med
Stud. 2021;1(1):40-62.
Hikmah, A SD. The relationship of piperaceae based on morphological character of vegetative organ in Meru Betiri National Park Jember East Java. In: The Second International Conference on Life Sciences and Biotechnology (ICOLIB).
; 2017:222-226.
Martha Perez Gutierrez R, Maria Neira Gonzalez A, HoyoVadillo C. Alkaloids from Piper: A Review of its Phytochemistry and Pharmacology. Mini Rev Med Chem. 2013;13(2):163-193. doi:10.2174/138955713804805148
Tiwari A, Mahadik KR, Gabhe SY. Piperine: A comprehensive review of methods of isolation, purification, and biological properties. Med Drug Discov. 2020;7:100027.
doi:10.1016/j.medidd.2020.100027
Stojanović-Radić Z, Pejčić M, Dimitrijević M, Aleksic A, Kumar NVA, Salehi B, Cho WC, Sharifi-Rad J. Piperine-A Major Principle of Black Pepper: A review of its bioactivity
and studies. Appl Sci. 2019;9(20):1-29.
doi:10.3390/app9204270
Meghwal M, Goswami TK. Piper nigrum and piperine: An update. Phyther Res. 2013;27(8):1121-1130. doi:10.1002/ptr.4972
Bano G, Raina RK, Zutshi U, Bedi KL, Johri RK, Sharma SC. 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
Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PSSR. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998;64(4):353-356. doi:10.1055/S-2006-957450
Bedada SK, Boga PK. The influence of piperine on the pharmacokinetics of fexofenadine, a P-glycoprotein substrate, in healthy volunteers. Eur J Clin Pharmacol.
;73(3):343-349. doi:10.1007/S00228-016-2173-3/FIGURES/1
Kolakota R, Bothsa A, Mugada V. Impact of N-acyl piperidine (Piperine) from Piper nigrum on the pharmacokinetics of CYP3A substrate almotriptan in rats. Trop J Nat Prod Res. 2020;4(8):378-384.
doi:10.26538/tjnpr/v4i8.10
Abdullahi ID, Yaro AH, Nazifi AB. Preliminary studies on the anti-inflammatory and analgesic effects of methanol leaf extract of Ficus asperifolia Miq. Trop J Nat Prod Res. 2020;4(3):85-90. doi:10.26538/tjnpr/v4i3.5
Shivananda A, Muralidhara Rao D, Jayaveera KN. Analgesic and anti-inflammatory activities of Citrus maxima (J.Burm.) Merr. in animal models. Res J Pharm Biol Chem Sci.2013;4(2):1800-1810.
Mishra PS, Phadnis P, Vyas S, Nyati P. Study of CNS activities of piperine Perse and its bio-enhancing effect on various drugs in experimental animal models. Int J Pharm Pharm Sci. 2016;8(4):135-140.
Diener HC, Montagna P, Gács G, Lyczak P, Schumann G, Zöller B, Mulder LJMM, Siegel J, Edson K. Efficacy and tolerability of diclofenac potassium sachets in migraine: A randomised, double-blind, cross-over study in comparison with diclofenac potassium tablets and placebo. Cephalalgia. 2006;26(5):537-547. doi:10.1111/j.1468-2982.2005.01064.x
Yuan J, Ma H, Cen N, Zhou A, Tao H. A pharmacokinetic study of diclofenac sodium in rats. Biomed Reports. 2017;7(2):179-182. doi:10.3892/br.2017.942
Tang W. The Metabolism of Diclofenac - Enzymology and Toxicology Perspectives. Curr Drug Metab. 2005;4(4):319-329. doi:10.2174/1389200033489398
Zi J, Liu D, Ma P, Huang H, Zhu J, Wei D, Yang J, Chen C. Effects of CYP2C9*3 and CYP2C9*13 on diclofenac metabolism and inhibition-based drug-drug interactions.
Drug Metab Pharmacokinet. 2010;25(4):343-350.
doi:10.2133/dmpk.DMPK-10-RG-009
Todd PA, Sorkin EM. Diclofenac sodium. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and
therapeutic efficacy. Drugs. 1988;35(3):244-285. doi:10.2165/00003495-198835030-00004
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):645-650.
doi:10.1124/jpet.102.034728
Shamsi S, Tran H, Tan RSJ, Tan ZJ, Lim LY. Curcumin, Piperine, and Capsaicin: A Comparative Study of SpiceMediated Inhibition of Human Cytochrome P450 Isozyme Activities. Drug Metab Dispos. 2017;45(1):49 LP - 55.
doi:10.1124/dmd.116.073213
Veeresha C, Sujath S, Rani TS. Effect of piperine on the pharmacokinetics and pharmacodynamics of glimepiride in
normal and streptozotocin - Induced diabetic rats. Nat Prod Commun. 2012;7(10):1283-1286.
doi:10.1177/1934578x1200701009
Zayed A, Babaresh WM, Darweesh RS, El-Elimat T, Hawamdeh SS. Piperine alters the pharmacokinetics and anticoagulation of warfarin in rats. J Exp Pharmacol.
;12:169-179. doi:10.2147/JEP.S257919
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):343-349. doi:10.1007/S00228-016-2173-3
Gilhotra N, Dhingra D. Possible involvement of GABAergic and nitriergic systems for antianxiety-like activity of piperine in unstressed and stressed mice. Pharmacol Rep. 2014;66(5):885-891. doi:10.1016/j.pharep.2014.05.008
Emon NU, Kaiser M, Islam M, Kabir MFI, Uddin MJ, Jyoti MA, Tanjil SM, Rasel ANM, Alam S, Islam MN. Anxiolytic and thrombolytic investigation of methanol extract of Pipernigrum L. Fruits and Sesamum indicum L. seeds. J Adv
Biotechnol Exp Ther. 2020;3(3):158-164.
doi:10.5455/jabet.2020.d121
Hritcu L, Noumedem JA, 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.
;11(1):1-13. doi:10.1186/s12993-015-0059-7
Ghosh S, Kumar A, Sachan N, Chandra P. Anxiolytic and antidepressant-like effects of essential oil from the fruits of
Piper nigrum Linn. (Black pepper) in mice: involvement of serotonergic but not GABAergic transmission system. Heliyon. 2021;7(4):e06884.
doi:10.1016/j.heliyon.2021.e06884
Pai H V, Upadhya SC, Chinta SJ, Hegde SN, Ravindranath V. Differential metabolism of alprazolam by liver and brain cytochrome (P4503A) to pharmacologically active metabolite. Pharmacogenomics J. 2002;2(4):243-258.
doi:10.1038/sj.tpj.6500115
Rezaee MM, Kazemi S, Kazemi MT, Gharooee S, Yazdani E, Gharooee H, Shiran MR, Moghadamnia AA.The effect of piperine on midazolam plasma concentration in healthy volunteers, a research on the CYP3A-involving metabolism. DARU, J Pharm Sci. 2014;22(1):1-7. doi:10.1186/2008-2231-22-8
Pattanaik S, Hota D, Prabhakar S, Kharbanda P, Pandhi P. Pharmacokinetic interaction of single dose of piperine with
steady-state carbamazepine in epilepsy patients. Phytother Res. 2009;23(9):1281-1286. doi:10.1002/ptr.2676
Berlińska A, Świątkowska-Stodulska R, Sworczak K. Factors Affecting Dexamethasone Suppression Test Results.
Exp Clin Endocrinol Diabetes. 2020;128(10):667-671.
doi:10.1055/a-1017-3217
Riaz M, Akram M, Egbuna C, Ifemeje J, Chikwendu J, Patrick-Iwuanyanwu K, Olatunde A, Tijjani H, Adetunji C, Shivamallu C, Olisah M, Uche C. Dexamethasone. Coronavirus Drug Discov Vol 1 SARS-CoV-2 Prev Diagnosis, Treat. Published online, 2022:169-179.
doi:10.1016/B978-0-323-85156-5.00028-6
Finch A, Pillans P. P-glycoprotein and its role in drug-drug interactions. Aust Prescr. 2014;37(4):137-139.
doi:10.18773/AUSTPRESCR.2014.050
Athukuri BL, Neerati P. Enhanced oral bioavailability of domperidone with piperine in male Wistar rats: Involvement
of CYP3A1 and P-gp inhibition. J Pharm Pharm Sci. 2017;20(1):28-37. doi:10.18433/j3mk72
Ueda K, Okamura N, Hirai M, et al. Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone but not
progesterone. J Biol Chem. 1992;267(34):24248-24252.
doi:10.1016/S0021-9258(18)35757-0