Based on Network Pharmacology and Gut Microbiota to Explore the Underlying Mechanism of Huangqi Gegen Decoction for Treating Metabolic-Associated Fatty Liver Disease.

Huangqi Gegen Decoction (HQGG) is composed of Astragali Radix and Puerariae Lobatae Radix, both of which are recognized as therapeutic agents and edible supplements, and has been reported as a potential treatment for metabolic-associated fatty liver disease (MAFLD). This study employed a comprehensive approach integrating network pharmacology, molecular docking, in vivo experimentation, and gut microbiota analysis to assess the efficacy of HQGG in treating MAFLD and to explore its molecular mechanisms. The results indicated that HQGG has significantly ameliorated hepatocellular injury, decreased liver inflammation, and oxidative stress in the HFD-induced MAFLD model rats. The network pharmacology identified 21 bioactive compounds, predicted 238 potential targets, and uncovered that the main active components of HQGG may regulate PTGS2, AKT1, MAPK1, JUN, and PPARG to confer their alleviating effects against MAFLD. HQGG also acted on various signaling pathways to treat MAFLD, such as the AGE-RAGE signaling pathway in diabetic complications, lipid and atherosclerosis, non-alcoholic fatty liver disease, and the IL-17 signaling pathway. The in vivo experiments revealed that HQGG may achieve the effect of anti-MAFLD by regulating the PPAR-γ/NF-κB signaling pathway. The results of gut microbiota analysis showed that HQGG could modulate the species structure and abundance, regulating gut microbiota imbalance of MAFLD rats. Overall, the results disclosed that HQGG can affect bacterial diversity and community structures in the gut and the PPAR-γ/NF-κB signaling pathway to treat MAFLD. This study systematically elucidated the potential mechanism of HQGG in treating MAFLD, providing a theoretical basis for the development and application of HQGG as a functional food for preventing MAFLD.