Network pharmacology-based identification of significant pathway for protection of Yinhuang granule in a mice model of metabolic-associated fatty liver disease

Metabolic-associated fatty liver disease (MAFLD) is a spectrum of liver disorders. Nonalcoholic steatohepatitis (NASH) is defined as a more serious process of MAFLD with liver inflammation. This study aims to observe the alleviation of Yinhuang granule (YHG), a Chinese patent medicine, on methionine and choline-deficient diet (MCD)-induced MAFLD in mice. Network pharmacology was used to analyze the improving effect of YHG on MAFLD and possible targets. MAFLD was induced in mice by MCD diet feeding for 6 weeks. In the last 2 weeks, the mice were orally given with YHG (400, 800 mg/kg) every day. Biochemical parameters of serum and liver, as well as hepatic gene expression were detected. Network pharmacology showed that YHG could improve MAFLD, inflammation, liver fibrosis, and oxidative stress. In animal experiments, YHG reduced hepatocellular damage and hepatic lipids accumulation which induced by MCD. In terms of liver inflammation, YHG attenuated MCD-induced liver inflammation in mice. YHG also inhibited the activation of hepatic stellate cells (HSCs) and alleviated liver fibrosis in MCD-fed mice. Through nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, YHG alleviated liver oxidative stress injury in mice which induced by MCD. YHG ameliorated MCD-induced MAFLD in mice by reducing hepatic lipids accumulation, alleviating liver oxidative, inflammatory injury and attenuating hepatic fibrosis.