Multi-Dimensional Analysis of the Mechanism ofTripterygium Wilfordii Hook．f． Compound Prescription Based on "Heterogeneous Restriction" in Reducing Hepatotoxicity from the Perspective of Substance-Metabolism-Toxicity Correlation

Tripterygium wilfordii Hook．f．(TWHF) is a commonly used Chinese medicine for the treatment of rheumatic immune diseases， but its side effects are obvious. Based on the theory of "heterogeneous restriction" proposed by the clinical application of TWHF compound prescriptions， with Qingluo Tongbi Fomula as a carrier， and clinically frequent hepatotoxicity as the starting point， the mechanism of TWHF compound compatibility to reduce liver injury was explored from the perspective of substance-metabolism-toxicity correlation in multiple dimensions. Qingluo Tongbi Fomula could reduce TWHF-induced hepatotoxicity by regulating the metabolism of TWHF and endogenous glucose and lipid， and improving lipid peroxidation damage， mitochondrial damage， and liver cell excessive autophagy and apoptosis via nuclear receptors-metabolizing enzymes， Nrf1-mitochondria and Nrf2-antioxidant pathways. The detoxicity effect of Chinese medicines with different functions through different links and targets of the cell and molecular regulatory network reflected the characteristics of "heterogeneous restriction". This research has provided a scientific basis for the original innovation of the theory of prescription compatibility and guiding the safe and reasonable clinical application of TWHF.