The effects of berberine hydrochloride on metabolic-associated fatty liver disease based on NLRP3 inflammatory signaling pathway

Background To explore the underlying molecular mechanisms of berberine hydrochloride on modulating inflammation of MAFLD rats. Methods A total of 42 Sprague-Dawley (SD) rats were randomly divided into 6 groups: a normal group (N) and five MAFLD groups induced by a high-fat diet, with or without berberine hydrochloride or glutathione treatment, in which glutathione served as a positive control. Liver pathology, liver function markers, blood lipids, blood glucose, gastrointestinal hormone changes, and the expression levels of the NOD-like receptor protein 3 (NLRP3) inflammasome signaling pathway and inflammatory factors were assessed. Results MAFLD rats induced by a high-fat diet exhibited an increased liver index, elevated blood glucose level, and abnormal activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lipid metabolism disorders. Berberine treatment reduced the liver index and blood glucose level in the model rats, while normalizing liver enzyme activity and lipid metabolism. Furthermore, MAFLD rats exhibited significant alterations in gastrointestinal hormone levels, including increased expression levels of VIP and NO, and decreased expression level of SP. Berberine intervention effectively reversed these effects. Additionally, the expression levels of proteins involved in the NLRP3 inflammatory pathway and pro-inflammatory cytokines (IL-1β and IL-18) were significantly elevated in MAFLD rats, and berberine significantly inhibited the activation of the NLRP3 pathway, thereby alleviating inflammation. Conclusion Berberine hydrochloride alleviated high-fat diet-induced MAFLD by reversing glucose, lipid, and enzyme metabolism disorders and by suppressing the NLRP3 inflammatory pathway. It could also regulate gastrointestinal motility by downregulating VIP and NO and upregulating SP in MAFLD rats.