Calycosin-7-O-β-D-glucoside alleviates non-alcoholic fatty liver disease by regulating short-chain fatty acids metabolism and metabolic regulators.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a metabolic stress liver injury disease caused by excessive fat deposition in hepatocytes. Astragalus memeranaceus Fisch., mainly consists of flavonoids, is considered to have good liver protection effects. This study aimed to explore the active ingredients and possible mechanisms of Astragalus flavone in the treatment of NAFLD. Network pharmacology and molecular docking were used to screen the active ingredients and targets of Astragalus flavone in the treatment of NAFLD, and were verified in vivo high-fat diet-induced mouse models. There were 89 predicted targets of 10 main compounds of Astragalus flavone in treating NAFLD, and the core genes involved PPAR-γ. Molecular docking results showed that all the 10 main components of Astragalus flavone had a strong binding activity with PPAR-γ, among which CG had the strongest binding ability. In vivo results showed that CG inhibited obesity, reduced the disorder of glucose and lipid metabolism, alleviated liver function injury and lipid accumulation, and improved the oxidative stress and inflammatory response of NAFLD mice, playing a positive role in the treatment of NAFLD. In addition, CG promoted the expression of AMPK, PPAR-γ, and Nrf2, inhibited the expressions of NF-кB, and regulated the metabolism of short-chain fatty acids (SCFAs) in NAFLD. In conclusion, CG, the main active component of Astragalus flavone, exerts a positive therapeutic effect on NAFLD, which is related to CG altering various energy sensors and metabolic regulators (PPAR-γ, AMPK, NF-кB, and Nrf2) that contribute to changes in intestinal SCFAs.