Metabolomics Reveals Shugan Formula Attenuates Anti‐Tuberculosis Drug‐Induced Liver Injury via Multi‐Pathway Metabolic Reprogramming in Rats

ABSTRACT Shugan Formula (SGF) shows clinical hepatoprotective effects, but its mechanism against anti‐tuberculosis drug‐induced liver injury (ATB‐DILI) remains unclear. This study employed LC–MS/MS‐based metabolomics to investigate SGF's protective effects in rats. ATB‐DILI was induced by oral isoniazid and rifampicin (100 mg·kg −1 each) for 14 days. During modeling, the rats in the treated groups received low, medium, or high doses of SGF via oral gavage, whereas the PC group was administered obeticholic acid. Serum biomarkers (ALT, AST, IL‐6, IL‐10, and TNF‐α), hepatic oxidative stress markers (MDA, SOD, GST, and GSH‐Px), liver histopathology, and serum metabolomics were assessed. SGF treatment significantly reduced serum ALT, AST, TNF‐α, and IL‐6 levels, decreased hepatic MDA and GST levels, and increased SOD and GSH‐Px activities. Metabolomics revealed that SGF attenuated metabolic perturbations induced by liver injury, with the high‐dose group being most effective. Key pathways involved amino acid metabolism, bile acid metabolism, and glycerophospholipid metabolism. This study provides scientific evidence for SGF in preventing and treating ATB‐DILI.