Network pharmacology analysis on mechanism of Jian Pi Qing Gan Yin decoction ameliorating high fat diet-induced non-alcoholic fatty liver disease and validated in vivo

Jian Pi Qing Gan Yin (JPQGY) has been used clinically to relieve non-alcoholic fatty liver disease (NAFLD) in China for decades; however, the underlying mechanisms of JPQGY remain unclear.We evaluated the effects and mechanisms of JPQGY and hepatic steatosis caused by the middle stage of 13-week-high-fat-diet-induced NAFLD in mice.Different dosages of JPQGY (5.5, 11, and 22 g/kg/day) were administered to NAFLD mice simultaneously. Body weight, body mass index (BMI), and liver lipid- and inflammation-related serum indicators were measured enzymatically. Liver samples were stained with Oil Red O and hematoxylin and eosin (H&E). Next, we performed a network pharmacology analysis and verified eight target genes mapping to NAFLD-related lipid metabolism pathways. The mRNA/protein expression was analyzed by real-time polymerase chain reaction (PCR) and western blotting.JPQGY significantly relieved histological damage (steatosis-inflammation-fibrosis), prevented the downregulation of AMPK and Pparα, and upregulated LXRα, Srebp-1c, F4/80, Nf-κb, and Cyp2e1 in the HFD-induced NAFLD mouse model.The present results suggest that chronic treatment with JPQGY ameliorated HFD-induced NAFLD in mice by targeting the first and second phases of hepatic steatosis by stimulating the AMPK/PPARα pathway and inhibiting the LXRα/Srebp1/Nf-κb pathway. Our findings provide evidence that supports the clinical use of this formula for high-fat diet-induced fatty liver disease.