Targeting insulin resistance: myricetin and isorhamnetin from <i>Hardwickia binata</i>, and luteolin from <i>Hedysarum alpinum</i> enhance glucose uptake and AMPK signaling in HepG2 cells

This study examined five plants (<i>Xylopia aethiopica, Agave sisalana, Hardwickia binata, Hedysarum alpinum, and Toxicodendron vernicifluum</i>) for their potential to address insulin resistance in type 2 diabetes. <i>In-vitro</i> assays showed that <i>H. binata</i> leaves and <i>H. alpinum</i> flowers inhibited α-glucosidase and α-amylase while enhancing glucose uptake in normal and insulin-resistant HepG2 cells. Phytochemical screening and SPE purification identified the key constituents responsible for the effects. The chromatographic and spectral analysis confirmed flavonoids in <i>H. binata</i> (myricetin, isorhamnetin, quercetin, kaempferol, and catechin) and <i>H. alpinum</i> (luteolin, quercetin, kaempferol, and apigenin). Myricetin, isorhamnetin, and luteolin significantly increased glucose uptake, enhanced hexokinase and pyruvate kinase activities, and promoted IRec and IRS-1 phosphorylation, modulating insulin signalling. They activated AMPK and Akt, with molecular docking confirming strong AMPK binding. These findings suggest that <i>H. binata</i>, <i>H. alpinum</i>, and their flavonoids are promising candidates for managing insulin resistance and type 2 diabetes, warranting further research.