Effects and therapeutic mechanism of Yinzhihuang on steatohepatitis in rats induced by a high‐fat, high‐cholesterol diet

OBJECTIVES: We aimed to investigate the therapeutic mechanism of Yinzhihuang (YZH) liquid, a traditional Chinese medicine mainly composed of extracts of four components, on nonalcoholic steatohepatitis (NASH) induced by a high‐fat, high‐cholesterol diet (HFHCD) in rats. METHODS: Altogether 30 Sprague‐Dawley rats were randomized into three groups: control, the model group (HFHCD + saline) and the treatment group (HFHCD + YZH). Liver histological features and serum biochemical parameters were assessed by the end of the 16th week. RNA sequencing and protein mass spectrometry detection were performed. The genes and proteins expressed differentially were subjected to KEGG pathway enrichment analysis and included in a network‐based regulatory model. RESULTS: The weight, liver and fat indices and serum alanine transaminase, aspartate transaminase and total cholesterol levels of the HFHCD + YZH group were all significantly lower than those of the HFHCD + saline group. Moreover, their hepatic steatosis, ballooning and lobular inflammation were relieved, and 64 hepatic genes and 73 hepatic proteins were found to be reversed in their expression patterns after YZH treatment (P < 0.05). The network‐based regulatory model showed that these deregulated genes and proteins were mainly involved in oxidative phosphorylation, Toll‐like receptor, nucleotide‐binding oligomerization domain‐like receptor, peroxisome proliferator‐activated receptor signaling, nuclear factor‐kappa B tumor necrosis factor signaling pathways and fatty acid metabolism. CONCLUSION: YZH could alleviate NASH in HFHCD‐fed rats by inhibiting lipogenesis, accelerating lipid β‐oxidation, alleviating oxidative stress and relieving necroinflammation in the liver.