Antidiabetic and Antioxidant Potential of Ethyl Iso-allocholate is Mediated Through Insulin Receptor/IRS-1/Akt/GLUT 4 Mediated Pathways: In vitro and In Silico Mechanisms

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DOI: 10.21522/TIJPH.2013.SE.24.03.Art015

Authors : Vishnu Priya Veeraraghavan, Selvaraj Jayaraman, Jerine I

Abstract:

Ethyl iso-allocholate (EIA) has emerged as a compound of interest due to its potential antioxidant and antidiabetic properties. This study aimed to evaluate the antidiabetic and antioxidant potential of EIA through a combination of in vitro assays and in silico analysis. The antioxidant activity of EIA was assessed using the DPPH radical scavenging assay. EIA demonstrated significant antioxidant activity with inhibition percentages of 29% at 100μg, increasing to 88% at 500μg, compared to Vitamin C, the standard antioxidant, which showed 41% and 95% inhibition, respectively. In terms of antidiabetic potential, EIA’s efficacy was evaluated through alpha-amylase and alpha-glucosidase inhibition assays. EIA exhibited dose-dependent inhibition of alpha-amylase, with a maximum inhibition of 71.3% at 50μg, compared to 96% by acarbose, a standard antidiabetic agent. Similarly, in the alpha-glucosidase assay, EIA showed up to 70.25% inhibition at 50μg, while acarbose achieved 95.7%. The cytotoxicity of EIA was assessed in 3T3-L1 cells over 48 hours, indicating a favorable safety profile. Additionally, Real-time PCR analysis revealed that EIA positively modulated the expression of key insulin signaling components (IR, IRS1, Akt, PI3K, and GLUT4) in 3T3-L1 cells. In silico molecular docking studies further supported these findings, showing strong binding affinities of EIA with insulin receptor (IR), IRS1, Akt, GLUT4, and PI3K, with the highest binding affinity observed with GLUT4 (-8.5 kcal/mol) and PI3K (-8.8 kcal/mol). These results suggest that EIA could be a promising candidate for further research into its therapeutic potential for diabetes and oxidative stress management.

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