Natural product puerarin activates Akt and ameliorates glucose and lipid metabolism dysfunction in hepatic cells

Abstract

Puerarin, one of the major isoflavonoid compounds isolated from Gegen, is widely used to treat glucose and lipid disorders. Identifying the mechanism of puerarin’s action against lipid and glucose metabolism dysfunction is very important for its application and development. Based on the structure of puerarin, different chemical probes were synthesized to capture and identify puerarin’s protein target. A membrane translocation assay was conducted to identify the interaction between puerarin and target proteins. The results show that puerarin targets the PH domain of Akt1, inhibits Akt1′s transmembrane effect and activates Akt1. Activated Akt1 improves the phosphorylation or activity of downstream proteins, such as GSK-3β and PDE3, and ultimately regulates glucose and lipid metabolism. Puerarin, as a dietary supplement, could target the PH domain of Akt1 to activate the insulin pathway and improve insulin resistance, thereby assisting in the regulation of glucose and lipid metabolism disorders.

Keywords

• Puerarin
• Akt
• Insulin signaling pathways
• Click reaction
• Glucose and lipid metabolism dysfunction