ISSN : 2663-2187

Swertiamarin and its analogues ameliorates diabetes-induced dyslipidemia by attenuating mitochondrial dysfunction through ACC-2 and CPT-1 signaling pathways

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Shikha Goswami , Kalicharan Sharma , Ritu , Ramesh K Goyal
» doi: 10.48047/AFJBS.6.Si3.2024. 2001-2026


The management of diabetes-induced dyslipidemia primarily focuses on ACC-2 and CPT-1 as key therapeutic targets. Dyslipidemia leads to impairment of mitochondrial function, which is intricately linked to the disruption of key enzymes ACC-2 and CPT-1, crucial in fatty acid synthesis and oxidation. Swertiamarin, which is an active constituent of Enicostemma littorale and has been reported to be effective in hyperglycemic condition. This prompted us to investigate the impact of Swertiamarin and its potent semi-synthetic derivatives in mitigating diabetes-induced dyslipidemia. Consequently, Swertiamarin analogues were designed and docked against the metabolic targets ACC-2 and CPT-1. To validate the docking results against the therapeutic targets, four compounds were selected for further synthesis and biological testing. Two compounds, SWL-2 and SWL-9 showed promising activity with IC50 values of 9.40 and 11.31 nM, respectively, against ACC-2 enzyme inhibition assay. In order to validate the potency and biological impacts of swertiamarin and its synthesized derivatives on the metabolic targets ACC-2 and CPT-1, a cell-based assay was performed using 3T3-L1 cells. Treatment with SWL-2 and SWL-9 (100ug/mL) showed better results compared to the standard (Metformin), as proven by a significant reduction in ACC-2 expression and an increase in CPT-1 concentrations. The findings of this study suggest that Swertiamarin and its derivatives have the potential to be used as lead compounds to manage dyslipidemia and other metabolic complications associated with diabetes.

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