Exploring the mechanism of 5,7-dimethoxy coumarin in the management of insulin resistance- A network pharmacology and experimental approach
Paper Details
Exploring the mechanism of 5,7-dimethoxy coumarin in the management of insulin resistance- A network pharmacology and experimental approach
Abstract
Insulin resistance (IR) is a pathological condition that plays a central role in the onset of type 2 diabetes mellitus and other related metabolic disorders. The present study explored the therapeutic potential of 5,7 Dimethoxy coumarin (5,7 DMC) against IR utilizing a network pharmacology and in vitro approaches. From the targets of 5,7 DMC and IR, 53 intersecting targets were identified. Network analysis identified TNF, NRF2, MAPK1, JAK1, GSTP1, AKT1, MTOR, FOS, PPARA and NFKBIA as hub genes. According to Gene Ontology and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis, these targets were primarily associated with insulin signaling, oxidative stress and inflammatory pathways. Furthermore, ADME profiling, indicated favourable pharmacokinetic characteristics, including a logP of 1.92, TPSA of 48.67 A2 and non-hepatoxic nature suggesting good oral bioavailability and cardiac safety of 5,7 DMC. Molecular docking studies confirmed high affinity interactions between 5,7 DMC with major target proteins, supporting its multi-target potential. In vitro experiments on high glucose induced insulin resistant-3T3-L1 adipocytes demonstrated that 5,7 DMC significantly improved the activities of antioxidant enzymes (SOD, CAT, GPx, GR, GST) and GSH levels with a decrease in lipid peroxidation markers. Further, it decreased the levels of proinflammatory cytokines (TNF-α, IL-6 and IL-1β) confirming its antioxidant and anti-inflammatory properties. Overall, the results suggest that 5,7 DMC is a potential therapeutic candidate for insulin resistance and its associated complications.
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