Anti-Obesity Properties of Black Pepper (Piper nigrum): Completing Puzzle using Computational Analysis

Authors

  • Nurun Nafi'atul Lailiyah Department of Biology, Faculty of Mathematic and Natural Science, Brawijaya University, Jl. Veteran, Malang, Jawa Timur, Indonesia 65145
  • Mutiara Dwirosita Ibrahim Department of Biology, Faculty of Mathematic and Natural Science, Brawijaya University, Jl. Veteran, Malang, Jawa Timur, Indonesia 65145
  • Chunafa Ayu Fitriani Department of Biology, Faculty of Mathematic and Natural Science, Brawijaya University, Jl. Veteran, Malang, Jawa Timur, Indonesia 65145
  • Feri Eko Hermanto Department of Biology, Faculty of Mathematic and Natural Science, Brawijaya University, Jl. Veteran, Malang, Jawa Timur, Indonesia 65145

DOI:

https://doi.org/10.21776/ub.jsmartech.2021.002.03.101

Keywords:

Ghrelin, GHSR, obesity, piperidine, piperine.

Abstract

Pepper (Piper nigrum) is one of the most common spices found in almost every food. Current knowledge informed that pepper regulates physiological activity in obesity. However, the exact mechanism is still poorly understood. This study determined the potential of piperine and piperidine as major compounds in pepper as GHSR-Ghrelin inhibitors due to over-activity of Ghrelin as appetite hormone in obesity. Molecular docking was performed to simulate the binding pattern of piperine and piperidine as GHSR-Ghrelin antagonist. The result showed that piperidine has a lower potential as GHSR-Ghrelin antagonist than piperine based on binding energy calculation and amino acid interaction. Further, piperine binding to GHSR could shift the Ghrelin binding site to the GHSR. In conclusion, piperine may act as an inhibitor of GHSR-Ghrelin interaction to prevent appetite behavior resulting in bodyweight loss in obesity.  

References

. Powell-Wiley, T.M., Poirier, P., Burke, L.E., Després, J.P., Gordon-Larsen, P., Lavie, C.J., Lear, S.A., Ndumele, C.E., Neeland, I.J., Sanders, P., and St-Onge, M.P., 2021, Obesity and cardiovascular disease: a scientific statement from the American Heart Association, Circulation, 143(21), e984-e1010.

. Popkin, B.M., Du, S., Green, W.D., Beck, M.A., Algaith, T., Herbst, C.H., Alsukait, R.F., Alluhidan, M., Alazemi, N., and Shekar, M., 2020, Individuals with obesity and COVID-19: a global perspective on the epidemiology and biological relationships, Obesity Reviews, 21(11), 1-17.

. Yosuke, I., Bo, Q., Jennifer, P., Sokol, R., and Gordon-Larsen, P., 2018, Epidemiology of obesity in adults: latest trends, Current Obesity Reports, 7(4), 276-288.

. Dinsa, G.D., Goryakin, Y., Fumagalli E., and Suhrcke M., 2012, Obesity and socioeconomic status in developing countries: a systematic review, Obesity Reviews, 13(11), 1067-1079.

. Monteiro, C.A., Moura, E.C., Conde, W.L., and Popkin, B.M., 2004, Socioeconomic status and obesity in adult populations of developing countries: a review, Bull World Health Organ, 82(12), 940-946.

. Kim, G.W., Lin, J.E., Valentino, M.A., Colon-Gonzalez, F., and Waldman, S.A., 2011, Regulation of appetite to treat obesity, Expert Reviews Clinical Pharmacology, 4(2), 243-259.

. Miller, G.D., 2017, Appetite regulation: hormones, peptides, and neurotransmitters and their role in obesity, American Journal of Lifestyle Medicine, 13(6), 586-601.

. Colldén G., Tschöp M.H., and Müller, T.D., 2017, Therapeutic potential of targeting the ghrelin pathway. International Journal of Molecular Sciences, 18(4), 798.

. Ãlvarez-Castro, P., Pena, L., and Cordido, F., 2013, Ghrelin in obesity, physiological and pharmacological considerations, Mini Reviews in Medicinal Chemistry, 13(4), 541-552.

. Makris, C.M., Alexandrou, A., Papatsoutsos, E.G., Malietzis, G., Tsilimigras, D.I., Guerron, A.D., and Moris, D., 2017, Ghrelin and obesity: identifying gaps and dispelling myths. A reappraisal. In Vivo, 31(6), 1047-1050.

. Horvath, T.L., Castañeda, T., Tang-Christensen M., Pagotto, U., and Tschöp, M.H., 2003, Ghrelin as a potential anti-obesity target, Current Pharmaceutical Design, 9(17), 1383-1395.

. Zhang, Q., Liu, S., Liu, R., Xue, H., and Wang, Y., 2014, Food policy approaches to obesity prevention: an international perspective. Current Obesity Reports, 3(2), 171-182.

. Perry, B., and Wang, Y., 2012, Appetite regulation and weight control: the role of gut hormones, Nutrition and Diabetes, 2(1), e26.

. Butt, M.S., Pasha, I., Sultan, M.T., Randhawa, M.A., Saeed, Farhan., and Ahmed, W., 2013, Black pepper and health claims: a comprehensive treatise. Critical Reviews in Food Science and Nutrition, 53(9), 875-886.

. Reshmi, S.K., Sathya, E., and Devi, P.S., 2010, Isolation of piperdine from Piper nigrum and its antiproliferative activity. African Journal of Pharmacy and Pharmacology, 4(8), 562-573.

. Srivastava, A.K., and Singh, V.K., 2017, Biological action of Piper nigrum - the king of spices. European Journal of Biological Research, 7(3), 223-233.

. Tiwari, A., Mahadik, K.R., and Gabhe, S.Y., 2020, Piperine: a comprehensive review of methods of isolation, purification, and biological properties, Medicine in Drug Discovery, 7, 100027.

. Stojanović-Radić, Z., PejÄić, M., Dimitrijević, M., Aleksić, A., Kumar, N.V.A., Salehi, B., Cho, W.C., and Sharifi-Rad, Javad., 2019, Piperine-A major principle of black pepper: a review of its bioactivity and studies, Applied Sciences, 9(20), 4270.

. Dallakyan, S., and Olson, A.J., 2015, Small-molecule library screening by docking with PyRx, Methods in Molecular Biology, 1263, 243-250.

. Trott, O., and Olson, A.J., 2010, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading, Journal of Computational Chemistry, 31(2), 455-461.

. Hermanto, F.E., Rifa’i, M., and Widodo, 2019, Potential role of glyceollin as anti-metastatic agent through transforming growth factor-β receptors inhibition signaling pathways: A computational study, AIP Conference Proceedings, 2155, 020035.

. Yan, Y., Tao, H., He, J., and Huang, S-Y., 2020, The HDOCK server for integrated protein-protein docking. Nature Protocols, 15, 1829-1852.

. Chen, D., Oezguen, N., Urvil, P., Ferguson, C., Dann, Sara M., and Savidge, T.C., 2016, Regulation of protein-ligand binding affinity by hydrogen bond pairing, Science Advances, 2(3), e1501240.

. Freitas, R.F. de, and Schapira, M., 2017, A systematic analysis of atomic protein-ligand interactions in the PDB, Medicinal Chemistry Communication, 8(10), 1970–1981.

. Du, Xing., Li, Y., Xia, Y-L., Ai S-M., Liang, J., Sang, P., Ji, X-L., and Liu, S-Q., 2016, Insights into protein-ligand interactions: mechanisms, models, and methods, International Journal of Molecular Sciences, 17(2), 144.

. Asakawa, A., Inui, A., Kaga, T., Katsuura, G., Fujimiya, M., Fujino, M.A., and Kasuga, M., 2003, Antagonism of ghrelin receptor reduces food intake and body weight gain in mice. Gut, 52(7), 947-952.

. Mohamed, G.A., Ibrahim, S.R.M., Elkhayat, E.S., El Dine, R.S., 2014, Natural anti-obesity agents, Bulletin of Faculty of Pharmacy, Cairo University, 52(2), 269-284.

. Rezaie, P., Mazidi, M., and Nematy, M., 2015, Ghrelin, food intake, and botanical extracts: a review, Avicenna Journal of Phytomedicine, 5(4), 271-281.

. Zanzer, C.Y., Plaza, M., Dougkas, A., Turner, C., Östman, E., 2018, Black pepper-based beverage induced appetite-suppressing effects without altering postprandial glycaemia, gut and thyroid hormones or gastrointestinal well-being: a randomized crossover study in healthy subjects, Food & Function, 9(5), 2774-2786.

. Du, Y., Chen, Y., Fu, X., Gu, J., Sun, Y., Zhang, Z., Xu, J., and Qin, L., 2020, Effects of piperine on lipid metabolism in high-fat diet induced obese mice, Journal of Functional Foods, 71, 104011.

. Shah, S.S., Shah, G.B., Singh, S.D., Gohil, P.V., 2011, Effect of piperine in the regulation of obesity-induced dyslipidemia in high-fat diet rats. Indian Journal of Pharmacology, 43(3), 296-299.

. Pastor, M.M., Capua, A.D., Ãlvarez, C.J.P., Hernández, M.D.D., Barbero, J.J., Casanueva, F.F., and Pazos, Y., 2010, Interaction between ghrelin and the ghrelin receptor (GHS-R1a), a NMR study living cells, Bioorganic & Medicinal Chemistry, 18, 1583-1590.

. Vortmeier, G., DeLuca, S.H., Heindl, S.E., Chollet, C., Scheidt, H.A., Sickinger, A.G.B., Meiler, J., and Huster, D., 2015, Integrating solid-state NMR and computational modeling to investigate the structure and dynamics of membrane-associated ghrelin, PLOS ONE, 10(3): e0122444.

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Published

2021-12-05

Issue

Vol. 2 No. 3 (2021)

Section

Articles

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