Exploring the Mechanism of Action of Sericin in Ameliorating non-Alcoholic Fatty Liver Disease in Mice Based on the Nrf2- GPX4/ NF-κB p65 Pathway

Objective: To explore the ameliorative effect and mechanism of action of sericin on liver injury in Non-Alcoholic Fatty Liver Disease (NAFLD) model mice. Methods: Mice were fed a high-fat diet for 8 weeks to establish NAFLD model mice. The NAFLD mice were then randomly divided into 6 groups and given 0, 250, 500, and 1000 mg/kg body weight of sericin, 1000 mg/kg sericin + ML385 (a protein inhibitor of Nrf2), and Zhibitai Capsules (a positive drug), by gavage, respectively. The levels of TC, TG, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in mouse serum and the levels of MDA, GSH, SOD, TNF-α, and IL-6 in liver tissues were measured. Pathological changes in liver tissues were evaluated using hematoxylin-eosin (HE) and Oil Red O staining. Protein expression of Nrf2, Keap1, HO-1, GPX4, and NF-κB p65 in liver tissues was detected by Western blotting, and the expression level of GPX4 in the liver was examined by immunohistochemistry. Results: Sericin and Zhibitai Capsules improved hepatic steatosis and lipid accumulation in NAFLD model mice. TC, TG, LDL-C, MDA, and TNF-α, IL-6 levels were down-regulated, and HDL-C and SOD levels were up-regulated. There was no significant difference in the expression of AST and ALT in all the groups. In addition, Sericin and Zhibitai Capsules upregulated the expression levels of Nrf2, keap1, HO-1, and GPX4 proteins and inhibited the expression of NF-κB p65 in the liver of NAFLD model mice. There was no significant difference in serum lipids and liver indices between the 1000 mg/kg sericin + ML385 group and the sericin dose groups. Conclusion: Sericin has an ameliorative effect on liver injury in NAFLD model mice by alleviating oxidative stress and inflammatory responses in liver injury. It remains to be explored whether this effect is regulated through the Nrf2- GPX4/ NF-κB p65 signaling pathway.