In-vitro and Insilico screening platform for the identification of aldose reductase inhibitors for antidiabetic lead compounds from Abutilon Indicum (L.)

Multimodal LLC

Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2020.10.31.363549v1?rss=1

Authors: L, L., V, V., Srihari, R., CN, P.

Abstract:
Introduction: Type 2 Diabetes Mellitus (T2DM) is a long-term metabolic disorder that primarily characterized by impaired insulin resistance to become hyperglycemia. People suffering from T2DM have a higher risk of developing various diseases but, on top of that, some diabetic drugs are also suspected of increasing the risk in some cases. Aldose reductase is a key target enzyme to catalyze the reduction of glucose to sorbitol and does not readily diffuse across cell membranes and cause retinopathy and neuropathy. The aldolase reductase inhibitors prevent the conversion of glucose to sorbitol and may have the capacity of preventing and / or treating several diabetic complications. It will be expected to be twofold in the subsequent decade due to intensification in the senile population with the number of people affected, thus adding to the liability on medical providers in poor developed countries using herbal medicine to control the diabetes. In recent investigation, the antidiabetic property of phytochemicals extracted from leafs of Abutilon indicum (L.) is elucidated using animal models. Materials and Methods: In the current study using aldose reductase enzyme assay inhibitor of Rat lens Aldose reductase were treated with A. indicum methanolic leaf extract at different concentrations (6.25, 12.5, 25, 50, 100, and 200microgram/mL). Copper sulphate was used as reference drug and docking studies to predict the screen the best aldose reductase inhibitor. Results and Discussion: The crude extract exhibited cytotoxicity against rat lens aldose reductase (IC50 = 135.8 {+/-} 956;g/L vs ref 13.60 {+/-} 956;g/L) using In Vitro. The docking is performed with 11 compounds shows Ertugliflozin, 9H-Cycloisolongifolene, 8-oxo and 7-hydroxycadalene showed a good binding interaction with aldose reductase. Conclusion: We are concluding that the invitro and in silico analysis helps researchers to utilize these compound for aldose reductase inhibitors and further can be used for clinical applications.

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