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Study of anti-diabetic activity of artesunate as an agonist to glp-1 by molecular docking and in-vitro analysis

Author: 
Sridharan, K., Vimal Anand, S., Dr. Saravanan, N., Dr. Ilamathi, M. and Dr. N. G. Ramesh Babu
Subject Area: 
Physical Sciences and Engineering
Abstract: 

The prevalence of diabetes mellitus (DM) is increasing with ageing of the population and life style changes associated with rapid urbanization and westernization. Though there are many drugs available in market to address this issue, the drug resistance is a real challenge to the pharmaceutical industry. To address this problem, we have selected a well-known anti-malarial drug, Artesunate (AS). With strong earlier reports on anti-inflammatory, anti-oxidant, anti-pyretic activities of this compound, we aim to study the anti-diabetic activity of AS. AS act as an agonist to Glucagon like protein (GLP) and can bind to GLP-1 Receptor, thus facilitating the glucose uptake by cells. Initially, a docking study was performed to check the affinity of AS with GLP-1R followed by prediction of ADME/Tox analysis. From the docking results, we were able to find that AS have good binding activity to GLP-1R and also have good drug likeliness properties. The computational result was then evaluated using biochemical assays and cell based assays in MIN6. α-amylase inhibitory effect and glucose uptake by yeast cells were studied. AS inhibits α-amylase and improve glucose uptake by cells at the concentration of 80µM. A cytotoxic analysis was performed using MTT assay. Upto 100µM, AS was non-toxic to cells. AS also induce the cell to produce insulin which was confirmed by measuring the Insulin secreted by the cells. This clearly proves that AS by binding to GLP-1R can provoke the cells to uptake glucose and secrete insulin as well. Thus, AS can be a potential anti-diabetic drug with high efficacy and low cytotoxicity compared to other drugs.

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