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

This study examined five plants (Xylopia aethiopica, Agave sisalana, Hardwickia binata, Hedysarum alpinum, and Toxicodendron vernicifluum) for their potential to address insulin resistance in type 2 diabetes. In-vitro assays showed that H. binata leaves and H. alpinum 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 H. binata (myricetin, isorhamnetin, quercetin, kaempferol, and catechin) and H. alpinum (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 H. binata, H. alpinum, and their flavonoids are promising candidates for managing insulin resistance and type 2 diabetes, warranting further research.