Study on the mechanism of Wuji Baifeng pill in alleviating rosuvastatin-induced liver injury via <i>SREBF2</i>

Abstract Objectives This study aims to elucidate the mechanism by which Wuji Baifeng pill alleviates rosuvastatin-induced liver injury, with the goal of providing a reference for precise clinical treatment. Methods This study utilized a high-fat diet (HFD) rat model to assess serum liver function indicators and the levels of inflammatory factors and oxidative stress markers in liver tissues. Additionally, quantitative reverse transcription PCR (qRT-PCR) was employed to measure the expression changes of key genes. Results Wuji Baifeng pill and rosuvastatin reduce triglycerides, low-density lipoprotein cholesterol (LDL-C) levels and diacylglycerol acyltransferase 1 ( DGAT1 ) expression, while increasing CGI-58 expression and high-density lipoprotein cholesterol (HDL-C) levels, with combined treatment showing the most significant effect. Wuji Baifeng pill significantly reverses rosuvastatin-induced increasing serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activities. It significantly reduces rosuvastatin-induced inflammation and oxidative stress. Ten intersection genes were identified, with sterol regulatory element binding protein 2 ( SREBF2 ) as a key therapeutic target of Wuji Baifeng pill. Wuji Baifeng pill significantly reversed rosuvastatin-induced increases in SREBF2 mRNA and protein levels. Overexpression of SREBF2 reversed Wuji Baifeng pill’s antioxidant and anti-inflammatory effects, reducing glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels and increasing IL-6 and IL-1β secretion. Conclusions Wuji Baifeng pill significantly inhibits drug-induced liver injury (DILI)-related inflammation and protects against rosuvastatin-induced liver injury through SREBF2 , offering a foundation for developing new therapies for DILI using its active ingredients.