A Discovery in Compatibility of Traditional Chinese Medicine: Spatholobus suberectus Dunn Suppresses Tripterygium wilfordii Hook. f.‐Induced Main Toxicity and Enhances Its Main Efficacy

ABSTRACT Tripterygium wilfordii Hook. f. (LGT) is commonly used in the treatment of rheumatoid arthritis, but its clinical application is limited by severe hepatotoxicity. Proper compatibility contributes to toxicity reduction and efficacy enhancement. Chinese Materia Medica textbooks record that compatibility with Spatholobus suberectus Dunn (JXT) can prevent the adverse effects of LGT. Nevertheless, the detoxification effect and underlying mechanism of compatibility with JXT in LGT‐induced hepatotoxicity are still unclear. First, the detoxification effect of JXT was evaluated through serum biochemical indicators and liver histopathology. Additionally, the attenuation mechanism was elucidated. The anti‐inflammatory and analgesic efficacy of LGT, after compatibility with JXT, was evaluated. Moreover, the main toxic component triptolide (TP) of LGT and the main active components of JXT were detected by high‐performance liquid chromatography (HPLC). Our findings revealed that compatibility with JXT significantly reduced serum levels of biochemical indicators and alleviated histopathological damage. Notably, the mRNA and protein expression levels of vascular endothelial growth factor A (VEGFA) and Flt‐1 were significantly downregulated. Moreover, compatibility with JXT enhanced the anti‐inflammatory and analgesic efficacy of LGT, while also reducing TP content. In conclusion, compatibility with JXT reduced LGT‐induced hepatotoxicity and potentiated its anti‐inflammatory and analgesic efficacy. The underlying attenuation mechanism might involve inhibiting VEGFA/Flt‐1 signaling and reducing TP content.