Sophora tonkinensis Alleviates Progression of Diethylnitrosamine-Induced Hepatocellular Carcinoma in Rats via Multitarget Regulation.

Sophora tonkinensis, a traditional Chinese medicine with heat-clearing, detoxifying, and throat-soothing properties, has shown potential in treating hepatitis, inhibiting tumors, and regulating immunity, but its active constituents and mechanisms remain unclear. We established a hepatocellular carcinoma (HCC) model in SD rats using diethylnitrosamine (DEN), with oral gavage of S. tonkinensis extract (STE) from Weeks 1 to 16, alongside model and normal control groups. Results showed that STE significantly reduced HCC incidence, reversed weight loss, decreased the number and volume of liver nodules, improved histopathological damage, and lowered serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and albumin (ALB) levels. Integrated transcriptomic (RNA-seq) and metabolomic (LC-MS/MS) analyses revealed enrichment in arachidonic acid and glycerophospholipid metabolism. Quantitative real-time polymerase chain reaction (qPCR) validation confirmed that STE restored hepatic lipid homeostasis and alleviated inflammation by activating the peroxisome proliferator-activated receptor (PPAR) pathway and suppressing the IL-17/TGF-β axis. These findings clarify the core mechanisms of STE in preventing and treating HCC, providing a theoretical basis for its precise clinical application.