Abstract:

The study was aimed at assessing the effects of Myricetin, a potent anti-cancer compound, targets the NRF2-Keap1 pathway in 3T3-L1 fibroblast cells, which is crucial in cancer progression, cell growth, and metastasis. Various assays have demonstrated myricetin's therapeutic potential. Antioxidant properties, confirmed by the DPPH assay, show dose-dependent free radical inhibition, with myricetin achieving 69.98% inhibition at 500 μg/ml (p<0.001). Anti-inflammatory assays reveal significant reductions in inflammatory markers, with inhibition rising to 74.75% at the same concentration (p<0.001). Gene expression studies highlight myricetin's impact on key components of the NRF2/Keap1 pathway, essential for cancer cell survival. In 3T3-L1 cells treated with myricetin, notable changes were observed in mRNA expression levels: IR (0.95±0.05, p<0.001), IL-1β (0.96±0.04, p<0.002), Keap1 (0.9±0.04, p<0.001), Glut4 (0.6±0.04, p<0.002), NRF2 (0.96±0.4, p<0.001), and NFκB (0.94±0.05, p<0.001). These findings suggest myricetin disrupts critical pathways, contributing to reduced inflammation and potential cancer inhibition. The MTT assay further indicates no cytotoxicity after 48 hours, supporting its safety profile. Molecular docking studies reveal strong binding affinities of myricetin to key pathway components, with Keap1 showing the highest affinity (-9.7 kcal/mol), followed by IR (-8 kcal/mol), NFκB (-6.9 kcal/mol), and NRF2 (-6.9 kcal/mol). IL-1β and Glut4 showed affinities of -7.1 and -7.2 kcal/mol, respectively, reinforcing myricetin's role in modulating the NRF2/Keap1 pathway. In summary, myricetin’s antioxidant, anti-inflammatory, and gene-modulatory activities, combined with its strong molecular interactions, position it as a promising therapeutic agent for both cancer and diabetes by modulating key cellular pathways.

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