Quzhi Formula Alleviates Nonalcoholic Steatohepatitis by Impairing Hepatocyte Lipid Accumulation and Inflammation via Bip/eIF2 alpha Signaling

Background and Aims: The Quzhi formula, a Chinese med-icine compound prescription, relieves nonalcoholic steato-hepatitis (NASH) symptoms. This study aimed to explore the mechanism of the Quzhi formula against NASH. Methods: A choline-deficient, L-amino acid-defined, high-fat diet induced a NASH mouse model and a free fatty acid-induced mouse hepatocyte cell model were used to evaluate the function of Quzhi formula in vivo and in vitro. Network pharmacol-ogy and molecular docking technology were performed to uncover the possible protective mechanisms of the Quzhi formula against NASH. Key factors in liver lipid metabolism and endoplasmic reticulum (ER) stress pathway were evalu-ated to verify the mechanism. Results: The positive contri-bution of the Quzhi formula on NASH was confirmed in vivo and in vitro. Abnormal accumulation of lipid in the liver and inflammatory responses were significantly decreased by the Quzhi formula. Network pharmacological analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the Quzhi formula protected against NASH by regulating ER stress and inflammatory responses, which was enhanced by further molecular docking analy-sis. In addition, mechanism exploration showed that Quzhi formula mainly reduced ER stress by downregulating Bip/eIF2 alpha signaling. Conclusions: The Quzhi formula protected against NASH by inhibiting lipid accumulation, ER stress, and inflammatory responses, which supports the potential use of Quzhi formula as an alternative treatment for NASH.