Molecular Docking Studies of Phenolic Compounds from Syzygium cumini with Multiple Targets of Type 2 Diabetes
Keywords:Alpha-glucosidase, Dipeptidyl peptidase 4, Glucagon receptor, Glucokinase, Glycogen synthase kinase 3, Phenolic compounds, Syzygium cumini
Treatment of type 2 diabetes without any side effects is still a challenge to the medical system. This leads to increasing demand for natural products with antidiabetic activity with fewer side effects. Syzygium cumini is a traditional herbal medicinal plant and is reported to possess a variety of pharmacological actions. It contains various types of chemical constituents including terpenoids, tannins, anthocyanins, flavonoids and other phenolic compounds. Some flavonoids and other phenolic compounds from S. cumini were reported in literature to have type 2 antidiabetic potential. The main objective of the current investigation was in silico screening of some phenolic compounds from S. cumini against multiple targets associated with type 2 diabetes to explore the mechanism of antidiabetic action and prediction of binding mode using molecular docking studies. In silico docking studies were performed for the selected molecules in the binding site of multiple targets associated with type 2 diabetes (α-glucosidas , dipeptidyl peptidase 4, glycogen synthase kinase 3, glucokinase and glucagon receptor). Amongst the compounds tested in silico, rutin showed appreciable binding with multiple targets of type 2 diabetes including α-glucosidase, dipeptidyl peptidase 4, glycogen synthase kinase 3, and glucagon receptor. Catechin was found to inhibit both α-glucosidase, and dipeptidyl peptidase 4. This information can be utilized for the design and development of potent multi-functional candidate drugs with minimal side effects for type 2 diabetes therapeuticsa.
Afify, A. M. R., Fayed, F. A., Shalaby, E. A. and El-Shemy, H. A. (2011). Syzygium cumini (pomposia) active principles exhibit potent anticancer and antioxidant activities. African Journal of Pharmacy and Pharmacology, 5(7), 948–956.
Avila-Pena, D., Pena, N., Quintero, S. L. and Suarez-Roca, H. (2007). Antinociceptive activity of Syzygium jambos leaves extract on rats. Journal of Ethnopharmacology, 112(2), 380–385. https://doi.org/10.1016/j.jep.2007.03.027
Ayyanar, M. and Subash-Babu, P. (2012). Syzygium cumini (L.) Skeels: a review of its phytochemical constituents and traditional uses. Asian Pacific Journal of Tropical Biomedicine, 2, 240–246. https://doi.org/10.1016/S2221-1691(12)60050-1
Bardy, G., Virsolvy, A., Quignard, J., Ravier, M., Bertrand, G., Dalle, S., et al. (2013). Quercetin induces insulin secretion by direct activation of L-type calcium channels in pancreatic beta cells. British Journal of Pharmacology, 169, 1102–1113. https://doi.org/10.1111/bph.12194
Bastaki, S. (2005). Diabetes mellitus and its treatment. International Journal of Diabetes Metabolism, 13, 111–134.
Bijauliya, R. K., Alok, S., Singh, M. and Mishra, S. B. (2017). Morphology, phytochemistry and pharmacology of Syzygium cumini (Linn.) - an overview. International Journal of Pharmaceutical Sciences and Research, 8(6), 2360–2371.
Brito, F. A., Lima, L. A., Ramos, M. F., Nakamura, M. J., Cavalher-Machados, S. C., Henrigues, M. G., et al. (2007). Pharmacological study of anti-allergic activity of Syzygium cumini (L) Skeels. Brazillian Journal of Medical and Biological Research, 40, 105–115. https://doi.org/10.1590/S0100-879X2007000100014
Cade, W. T. (2008). Diabetes-related microvascular and macrovascular diseases in the physical therapy setting. Physical Therapy, 88, 1322–1335. https://doi.org/10.2522/ptj.20080008
Chagas, V. T., França, L. M., Malik, S. and Paes, A. M. A. (2015). Syzygium cumini (L.) skeels: a prominent source of bioactive molecules against cardiometabolic diseases. Frontiers in Pharmacology, 6, Article 259. https://doi.org/10.3389/fphar.2015.00259
Charaya, N., Pandita, D., Grewal, A. S. and Lather, V. (2018). Design, synthesis and biological evaluation of novel thiazol-2-yl benzamide derivatives as glucokinase activators. Computational Biology and Chemistry, 73, 221–229. https://doi.org/10.1016/j.compbiolchem.2018.02.018
Chaturvedi, A., Bhawani, G., Agarwal, P. K., Goel, S., Singh, A. and Goel, R. K. (2009). Ulcer healing properties of ethanolic extract of Eugenia jambolana seed in diabetic rats : study on gastric mucosal defensive factors. Indian Journal of Physiology and Pharmacology, 53, 16–24.
Esmaeili, M. A., Zohari, F. and Sadeghi, H. (2009). Antioxidant and protective effects of major flavonoids from Teucriumpolium on beta-cell destruction in a model of streptozotocin-induced diabetes. Planta Medica, 75, 1418–1420. https://doi.org/10.1055/s-0029-1185704
Espinoza-Fonseca, L. M. (2006). The benefits of the multi-target approach in drug design and discovery. Bioorganic & Medicinal Chemistry, 14(4), 896–897. https://doi.org/10.1016/j.bmc.2005.09.011
Goyal, P. K., Verma, P., Sharma, P., Parmar, J. and Agarwal, A. (2010). Evaluation of anti-cancer and anti-oxidative potential of Syzygium cumini against benzo[a]pyrene (BaP) induced gastric carcinogenesis in mice. Asian Pacific Journal of Cancer Prevention, 11, 753–758.
Grewal, A. S., Sekhon, B. S. and Lather, V. (2014). Recent updates on glucokinase activators for the treatment of type 2 diabetes mellitus. Mini Reviews in Medicinal Chemistry, 14(7), 585–602. https://doi.org/10.2174/1389557514666140722082713
Grewal, A. S., Bhardwaj, S., Pandita, D., Lather, V. and Sekhon, B. S. (2016). Updates on aldose reductase inhibitors for management of diabetic complications and non-diabetic diseases. Mini Reviews in Medicinal Chemistry, 16, 120–162. https://doi.org/10.2174/1389557515666150909143737
Grewal, A. S., Lather, V., Pandita, D. and Bhayana, G. (2017). Synthesis, docking and biological evaluation of phenylacetic acid and trifluoromethylphenyl substituted benzamide derivatives as potential PPARδ agonists. Letters in Drug Design and Discovery, 14(11), 1239–1251.
Haraguchi, H., Kanada, M., Fukuda, A., Naruse, K., Okamura, N. and Yagi, A. (1998). An inhibitor of aldose reductase and sorbitol accumulation from Anthocepharus chinensis. Planta Medica, 64, 68–69. https://doi.org/10.1055/s-2006-957369
Herculano, E. D. A., Costa, C. D. F., Rodrigues, A. K. B. F., Junior, J. X. A., Santana, A. E. G., França, P. H. B. et al. (2014). Evaluation of cardiovascular effects of edible fruits of Syzygium cumini Myrtaceae (L) skeels in rats. Tropical Journal of Pharmaceutical Research, 13(11), 1853–1861. https://doi.org/10.4314/tjpr.v13i11.12
International Diabetes Federation. Available at: https://www.idf.org/e-library/epidemiology-research/diabetes-atlas/134-idf-diabetes-atlas-8th-edition.html (Accessed 10 July 2018).
Kamalakkannan, N. and Prince, P. S. M. (2006). Antihyperglycaemic and antioxidant effect of rutin, a polyphenolic flavonoid, in streptozotocin-induced diabetic Wistar rats. Basic and Clinical Pharmacology and Toxicology, 98, 97–103. https://doi.org/10.1111/j.1742-7843.2006.pto_241.x
Kohei, K. (2010). Pathophysiology of type 2 diabetes and its treatment policy. Japan Medical Association Journal, 53, 41–46.
Kumar, A., Padmanabhan, N. and Krishnan, M. R. V. (2007). Central Nervous system activity of Syzygium cumini seed. Pakistan Journal of Nutrition, 6(6), 698–700. https://doi.org/10.3923/pjn.2007.698.700
Kumar, R., Jayachandran, T., Deecaraman, M., Aravindan, P., Padmanabhan, N. and Krishan, M. R. V. (2008). Anti-diabetic activity of Syzygium cumini and its isolated compound against streptozotocininduced diabetic rats. Journal of Medicinal Plants Research, 2(9), 246–249.
Kumar, S., Saini, M., Kumar, V., Prakash, O., Arya, R, Rana, M., et al. (2012). Traditional medicinal plants curing diabetes: a promise for today and tomorrow. Asian Journal of Traditional Medicines, 7, 178–188.
Lagorce, D., Bouslama, L., Becot, J., Miteva, M. A. and Villoutreix, B. O. (2017). FAF-Drugs4: free ADMEtox filtering computations for chemical biology and early stages drug discovery. Bioinformatics, 33(22), 3658–3660. https://doi.org/10.1093/bioinformatics/btx491
Liu, I.-M., Tzeng, T.-F., Liou, S.-S. and Lan, T.-W. (2007). Myricetin, a naturally occurring flavonol, ameliorates insulin resistance induced by a highfructose diet in rats. Life Sciences, 81, 1479–1488. https://doi.org/10.1016/j.lfs.2007.08.045
Mahapatra, P. K., Chakraborty, D. and Chaudhari, A. K. N. (1986). Anti-inflammatory and antipyretic activities of Syzygium cumini. Planta Medica, 6, 540. https://doi.org/10.1055/s-2007-969339
Miteva, M. A., Violas, S., Montes, M., Gomez, D., Tuffery, P. and Villoutreix, B. O. (2006). FAF-Drugs: free ADME/tox filtering of compound collections. Nucleic Acids Research, 34, W738–W744. https://doi.org/10.1093/nar/gkl065
Miteva, M. A., Guyon, F. and Tufféry, P. (2010). Frog2: Efficient 3D conformation ensemble generator for small compounds. Nucleic Acids Research, 38, W622–627. https://doi.org/10.1093/nar/gkq325
Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S., et al. (2009). Autodock4 and AutoDockTools4: automated docking withselective receptor flexiblity. Journal of Computational Chemistry, 16, 2785–2791. https://doi.org/10.1002/jcc.21256
Muruganandan, S., Srinivasan, K., Chandra, S., Tandan, S. K., Lal, J. and Raviprakash, V. (2001). Anti-inflammatory activity of Syzygium cumini bark. Fitoterapia, 72(4), 369–375. https://doi.org/10.1016/S0367-326X(00)00325-7
Nair, L. K., Begum, M. and Geetha, S. (2013). In vitro-antioxidant activity of the seed and leaf extracts of Syzygium cumini. IOSR Journal of Environmental Science, Toxicology and Food Technology, 7(1), 54–62. https://doi.org/10.9790/2402-0715462
Namba, T., Tsunezuka, M., Dissanayake, D. M. R. B., Upali, P., Keiko, S., Nobuko, K., el al. (1985). Studies on dental caries prevention by traditional medicines part VII, screening of Ayurvedic medicines for antiplaque action. Japanese Journal of Pharmacognosy, 39(2), 146–153.
Ohnishi, M., Matuo, T., Tsuno, T., Hosoda, A., Nomura, E., Taniguchi, H., et al. (2004). Antioxidant activity and hypoglycemic effect of ferulic acid in STZinduced diabetic mice and KK-Ay mice. Biofactors, 21(1–4), 315–319. https://doi.org/10.1002/biof.552210161
Olokoba, A. B., Obateru, O. A. and Olokoba, L. B. (2012). Type 2 diabetes mellitus: a review of current trends. Oman Medical Journal, 27, 269–273. https://doi.org/10.5001/omj.2012.68
Osadebe, P. O., Odoh E. U. and Uzor, P. F. (2014). Natural products as potential sources of antidiabeticdrugs. British Journal of Pharmaceutical Research, 4(17), 2075–2095. https://doi.org/10.9734/BJPR/2014/8382
Patil, R., Patil, R., Ahirwar, B. and Ahirwar, D. (2011). Current status of Indian medicinal plants with antidiabetic potential: a review. Asian Pacific Journal of Tropical Biomedicine, 1(2), S291–S298. https://doi.org/10.1016/S2221-1691(11)60175-5
Prateek, A., Meena, R. K. and Yadav, B. (2015). Antimicrobial activity of Syzygium cumini. Indian Journal of Applied Research, 5(9), 63–66.
Rajasekaran, M., Bapana, J. S., Lakshmanan, A. G., Nair, R., Veliath, A. J. and Panchanadam, M. (1998). Antifertility effect in male rats of oleanolic acid, a triterpene from Eugenia jambolana flowers. Journal of Ethnopharmacology, 24, 115–121. https://doi.org/10.1016/0378-8741(88)90142-0
Ramsay, R. R., Popovic-Nikolic, M. R., Nikolic, K., Uliassi, E. and Bolognesi, M. L. (2018). A perspective on multi-target drug discovery and design for complex diseases. Clinical and Translational Medicine, 7(1), 3. https://doi.org/10.1186/s40169-017-0181-2
Ramya, S., Neethirajan, K. and Jayakumararaj, R. (2012). Profile of bioactive compounds in Syzygium cumini-a review. Journal of Pharmacy Research, 5, 4548–4553.
Rizvi, S. I. and Mishra, N. (2013). Traditional Indian medicines used for the management of diabetes mellitus. Journal of Diabetes Research, 2013, Article ID 712092. https://doi.org/10.1155/2013/712092
Scotti, L., Mendonca, F. J. Jr., Ishiki, H. M., Ribeiro, F. F., Singla, R. K., Barbosa Filho, J. M., et al. (2017). Docking Studies for Multi-Target Drugs. Current Drug Targets, 18(5), 592–604. https://doi.org/10.2174/1389450116666150825111818
Shamkuwar, Prashant, B., Pawar, D. P. and Chauhan, S. S. (2012). Antidiarrhoeal activity of seeds of Syzygium cumini L. Journal of Pharmacy Research, 5(12), 5537.
Sharma, B., Viswanath, G., Salunke, R. and Roy, P. (2008). Effects of flavonoid-rich extract from seeds of Eugenia jambolana (L.) on carbohydrate and lipid metabolism in diabetic mice. Food Chemistry, 110, 697–705. https://doi.org/10.1016/j.foodchem.2008.02.068
Sood, R., Swarup, D., Bhatia, D., Kulkarni, D. D., Dey, S., Saini, M., et al. (2012). Antiviral activity of crude extracts of Eugenia jambolana Lam. against highly pathogenic avian influenza (H5N1) virus. Indian Journal of Experimental Biology, 50, 179–218.
Srivastava, S. and Chandra, D. (2013). Pharmacological potentials of Syzygium cumini: a review. Journal of the Science of Food and Agriculture, 93, 2084–2093. https://doi.org/10.1002/jsfa.6111
Swami, S. B., Thakor, N. S., Patil, M. M. and Haldankar, P. M. (2012). Jamum (Syzygium cumini (L.)): a review of its food and medicinal uses. Food and Nutrition Sciences, 3(8), 1100–1117. https://doi.org/10.4236/fns.2012.38146
Tripathi, A. K. and Kohli, S. (2014). Pharmacognostical standardization and antidiabetic activity of Syzygium cumini (Linn.) barks (Myrtaceae) on streptozotocininduced diabetic rats. Journal of Complementary and Integrative Medicine, 11(2), 71–81. https://doi.org/10.1515/jcim-2014-0011
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, 455–461.
Veigas, J. M., Narayan, M. S., Laxman, P. M. and Neelwarne, B. (2007). Chemical nature stability and bioefficacies of anthocyanins from fruit peel of Syzygium cumini Skeels. Food Chemistry, 105, 619–627. https://doi.org/10.1016/j.foodchem.2007.04.022
Veigas, J. M., Shrivasthava, R. and Neelwarne, B. (2008). Efficient amelioration of carbon tetrachloride induced toxicity in isolated rat hepatocytes by Syzygium cumini Skeels extract. Toxicology In vitro, 22, 1440–1446. https://doi.org/10.1016/j.tiv.2008.04.015
Wein, S., Behm, N., Petersen, R. K., Kristiansen, K. and Wolffram, S. (2010). Quercetin enhances adiponect in secretion by a PPAR-gamma independent mechanism. European Journal of Pharmaceutical Sciences, 41, 16–22. https://doi.org/10.1016/j.ejps.2010.05.004
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Based on a work at https://jptrm.chitkara.edu.in