The flavonoid baicalin improves glucose metabolism by targeting the PH domain of AKT and activating AKT/GSK3β phosphorylation

Baicalin is one of the main Flavonoids of the dried root of Scutellaria baicalensis Georgi and is reported to exert beneficial effects on the regulation of glucose/lipid metabolism. However, understanding its specific target and unique mechanism for improving glucose utilization is a challenge. In this paper, target fishing with a baicalin probe reveals that baicalin interacts with Akt. An immunofluorescence assay further demonstrates the colocalization of baicalin with Akt in the cytoplasm. A competitive test and virtual docking show that baicalin might bind to the pleckstrin homology domain of Akt. This specific binding hampers Akt membrane translocation, activates the phosphorylation of Akt on Ser473, induces the downstream glycogen synthase kinase 3β activation, and affects glycogen synthesis.