Rhodiola crenulata extract suppresses hepatic gluconeogenesis via activation of the AMPK pathway

BackgroundRhodiola, a popular herb, has been used for treating high altitude sicknesses, depression, fatigue, and diabetes. However, the detailed mechanisms by which Rhodiola crenulata functions in the liver need further clarification.PurposeThe current study was designed to examine the effects of Rhodiola crenulata root extract (RCE) on hepatic glucose production.MethodsHuman hepatoma HepG2 cells were treated with RCE for 6 h. Glucose production, the expression level of p-AMPK, and the expression of key gluconeogenic genes were measured. The effects of RCE were also studied in Sprague–Dawley (SD) rats. The efficacy and underlying mechanism of RCE in the liver were examined.ResultsRCE significantly suppressed glucose production and gluconeogenic gene expression in HepG2 cells while activating the AMPK signaling pathway. Interestingly, RCE-suppressed hepatic gluconeogenesis was eliminated by an AMPK-specific inhibitor, but not by the PI3K/AKT-specific inhibitor. In addition, oral administration of RCE significantly increased phosphorylated AMPK levels and inhibited gluconeogenic gene expression in the rat liver. Furthermore, RCE treatment also decreased plasma glucose concentration in rats.ConclusionWe present in vitro and in vivo evidence that RCE might exert the glucose-lowering effect partly by inhibiting hepatic gluconeogenesis through activating the AMPK signaling pathway. These findings provide evidence that Rhodiola crenulata may be helpful for the management of type II diabetes.