Prenylated flavonoid fractions from Glycyrrhiza glabra alleviate insulin resistance in HepG2 cells by regulating the ERK/IRS-1 and PI3K/Akt signaling pathways

Insulin resistance (IR) is a key factor in the pathogenesis of disrupted glucose metabolism. Although the extract of Glycyrrhiza glabra has shown significant hypoglycemic activity, its bioactive components remain to be identified, and their mechanisms of action, especially on hepatocyte glucose metabolism, are yet to be explored. In the present study, the primary compounds from Glycyrrhiza glabra [named prenylated flavonoid fractions (PFFs)] have been identified and their chemical structures have been elucidated. The therapeutic effects of PFFs extracted from G. glabra on glucose metabolism disorders and IR in high insulin-induced insulin-resistant HepG2 (IR-HepG2) cells have been determined. Glabridin (GLD) was used as a control. The results indicated that, similar to GLD, PFFs increased glucose consumption, glucose uptake, and translocation of glucose transporter 4 to the plasma membrane in IR-HepG2 cells. In addition, they enhanced the activities of glycogen synthase, Glucokinase, and Pyruvate Kinase, while reducing the activities of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Furthermore, they activated the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway and suppressed the extracellular signal-regulated kinase/Insulin Receptor substrate-1 (ERK/IRS-1) pathway. These findings suggest that, similar to GLD, PFFs can alleviate impaired glucose metabolism and alleviate IR in IR-HepG2 cells.Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.The authors and their affiliations have been confirmed as correct.

ERK/IRS-1; Insulin resistance; Network pharmacology; PI3K/Akt; Prenylated flavonoid fractions from Glycyrrhiza glabra.