Ethanol extract of Atractylodis macrocephalae Rhizoma ameliorates insulin resistance and gut microbiota in type 2 diabetic db/db mice

•This is the first study on the anti-diabetic effect of AMK in db/db mice.•AMK attenuated insulin resistance and regulated glucose and lipid metabolism.•AMK increased the abundance of B. thetaiotaomicron and M. smithii in gut microbiota.•AMK regulated GLP-1R/PI3K/PDX-1 signaling pathway in db/db mice. Atractylodis macrocephalae Rhizoma is widely used as a functional food in Asia. It can enhance glucose and lipid metabolism in the obesity patients with adiposity. In this study, therapeutic effects and the underlying molecular mechanisms of its ethanol extract (AMK) were investigated in db/db mice. Oral treatment with AMK at a dose of 100 mg/kg for three weeks significantly decreased the blood glucose, serum triacylglycerol, total cholesterol, HOMA-IR, endotoxin and IL-1β. Besides, AMK increased the abundance of Bacteroides thetaiotaomicron and Methanobrevibacter smithii in gut microbiota and improved the histological abnormalities of liver, adipocytes, pancreas and small intestine in diabetic mice. Moreover, AMK upregulated the expressions of GLP-1R, PI3K and PDX-1, but downregulated FOXO1 and NF-κB p65 in liver and pancreas tissues of diabetic mice. These results suggested that AMK ameliorated glucose metabolism by regulating GLP-1R/PI3K/PDX-1 pathway and gut microbiota, and it could be developed as a medicinal herb for T2DM treatment.