Molecular Docking and Pharmacological Property Analysis of Antidiabetic Agents from Medicinal Plants of Bangladesh against Type II Diabetes: A Computational Approach
Abstract
Diabetes Mellitus (DM) is a metabolic disorder which affects the people of almost all ethnic groups around the world severely. The effect of this disease involves lifelong suffering and has no permanent cure till now. Although different medications are available in the market but they are not accessible to every person due to their high cost, requirement of frequent administration and inability to alleviate diabetes permanently. Plant derived compounds are being commonly used by many people, specifically by those in rural areas of many countries as ayurvedic source of antidiabetic agents and these are more preferable to everyone due to their less toxicity and side effects. These compounds work by variety of mechanisms which involve different interactions between effective compounds and target proteins in the metabolic pathway. Molecular docking study helps in determining the interaction between specific ligands and receptors to specify the best lead that fits the target. This study has been designed to investigate the interactions with the aid of computational simulation tool between medicinal plant derived antidiabetic agents (Aegeline, Gallic Acid, Mangiferin and Quercetin) and a glucose metabolism regulatory target enzyme involved in type II diabetes, Glycogen Synthase Kinase-3 Beta (GSK3B) to assist potential antidiabetic drug search from natural source.
ADME/T test assists in determining various physicochemical and pharmacological properties of lead molecules like their extent of adsorption inside the cell, extent of metabolism, solubility, blood brain barrier permeability, mutagenicity, carcinogenicity etc. which are the major prerequisites before marketing a drug. Quercetin performed well in overall experiment suggesting the best finding of the experiment.
However, further in vitro/in vivo study is required to find out the best remedy of diabetes.
References
2. Apontes P, Liu Z, Su K, Benard O, Youn DY, Li X, Li W, Mirza RH, Bastie CC, Jelicks LA, Pessin JE 2014: Mangiferin stimulates carbohydrate oxidation and protects against metabolic disorders induced by high-fat diets; Diabetes; 63(11); 3626-36.
3. Cheng FC, Shen SC, Wu JS (2009); Effect of guava (Psidium guajava L.) leaf extract on glucose uptake in rat hepatocytes; Journal of food science; 74(5); H132-8
4. Clark Jr, C.M. and Lee, D.A., (1995); Prevention and treatment of the complications of diabetes mellitus;New England journal of medicine; 332(18); 1210-1217.
5. Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA. (1995); Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B; Nature; 378(6559); 785.
6. Dearden, J. C. (2007); In silicoprediction of ADMET properties: how far have we come? ; Expert Opinion on Drug Metabolism & Toxicology; 3(5); 635–639.
7. Ferreira, L., dos Santos, R., Oliva, G. and Andricopulo, A., (2015); Molecular docking and structure-based drug design strategies; Molecules; 20(7); 13384-13421.
8. Grimes, C.A. and Jope, R.S., (2001); The multifaceted roles of glycogen synthase kinase 3β in cellular signaling; Progress in neurobiology; 65(4); pp.391-426.
9. Guedes IA, de Magalhães CS, Dardenne LE. (2014); Receptor–ligand molecular docking; Biophysical reviews; 6(1); 75-87.
10. Hasan T, Sultana M. (2018); Antidiabetic Potency of Bangladeshi Medicinal Plants; J Ayurvedic Herb Med; 4(1); 35-42.
11. Lipinski, C.A., Lombardo, F., Dominy, B.W. and Feeney, P.J., (1997); Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings; Advanced drug delivery reviews; 23(1-3); 3-25.
12. Marles, R.J. and Farnsworth, N.R., (1995); Antidiabetic plants and their active constituents; Phytomedicine; 2(2); 137-189.
13. Martinez, A., Castro, A., Dorronsoro, I., & Alonso, M. (2002); Glycogen synthase kinase 3 (GSK-3) inhibitors as new promising drugs for diabetes, neurodegeneration, cancer, and inflammation; Medicinal Research Reviews; 22(4); 373–384
14. Morris, G.M. and Lim-Wilby, M., (2008); Molecular docking. In Molecular modeling of proteins (pp. 365-382). Humana Press.
15. Narender T, Shweta S, Tiwari P, Reddy KP, Khaliq T, Prathipati P et al. (2007); Antihyperglycemic and antidyslipidemic agent from Aegle marmelos; Bioorganic & medicinal chemistry letter 17(6); 1808-11.
16. Nebert, D.W. and Russell, D.W., (2002); Clinical importance of the cytochromes P450. ; The Lancet; 360(9340); 1155-1162.
17. Patel, S., Doble, B.W., MacAulay, K., Sinclair, E.M., Drucker, D.J. and Woodgett, J.R., (2008); Tissue-specific role of glycogen synthase kinase 3β in glucose homeostasis and insulin action; Molecular and cellular biology; 28(20); 6314-6328.
18. Pollastri, M.P., 2010. Overview on the Rule of Five. Current protocols in pharmacology, 49(1), pp.9-12.
19. Roglic G (2016); WHO Global report on diabetes: A summary; Int J Non-Commun Dis;1; 3-8
20. Sabu MC, Kuttan R (2009); Antidiabetic and antioxidant activity of Terminalia belerica. Roxb; Indian journal of experimental biology; 47(4); 270-5.
21. Shukia, R., Sharma, S.B., Puri, D., Prabhu, K.M. and Murthy, P.S., (2000); Medicinal plants for treatment of diabetes mellitus. Indian Journal of Clinical Biochemistry; 15(1);169-177.
22. Sutherland, C., Leighton, I.A. and Cohen, P., (1993); Inactivation of glycogen synthase kinase-3β by phosphorylation: new kinase connections in insulin and growth-factor signalling; Biochemical Journal; 296(1); 15-19.
23. Wang, J. and Skolnik, S., (2009); Recent advances in physicochemical and ADMET profiling in drug discovery; Chemistry & biodiversity; 6(11); 1887-1899.
24. Tapsell LC, Hemphill I, Cobiac L, Sullivan DR, Fenech M, Patch CS, Roodenrys S, Keogh JB, Clifton PM, Williams PG, Fazio VA (2006); Health benefits of herbs and spices: the past, the present, the future; The Medical Journal of Australia; 185(4); S1-S24.
