Qingluo Tongbi Formula attenuates Tripterygium wilfordii Hook. f.-induced hepatic metabolic dysfunction and oxidative stress via the SIRT1/HIF-1α pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium wilfordii Hook. f. (TW) is widely used to treat autoimmune and inflammatory diseases, but its clinical utility is limited by hepatotoxicity. Qingluo Tongbi Formula (QTF), a classic multi-herb prescription for rheumatoid arthritis containing TW, has shown good efficacy with fewer liver adverse effects in clinical practice.

AIM OF THE STUDY: To evaluate whether QTF alleviates TW-induced hepatotoxicity and to elucidate the underlying metabolic and molecular mechanisms.

MATERIALS AND

METHODS

A TW-induced hepatotoxicity model was established in C57BL/6J mice treated with TW alone, QTF, or TW combined with individual constituent herbs. Liver injury, oxidative stress, and lipid peroxidation were evaluated by serum biochemistry and histopathology. Untargeted metabolomics was performed to profile hepatic energy metabolism. In vitro, triptolide-injured AML12 hepatocytes were used to evaluate the protective effects of catalpol (CAT) and Panax notoginseng saponins (PNS) on cellular bioenergetics and the sirtuin 1 (SIRT1)/hypoxia-inducible factor-1α (HIF-1α) axis.

RESULTS

In vivo, QTF significantly attenuated TW-induced hepatotoxicity, hypoglycaemia, oxidative stress, and lipid peroxidation, and partially normalized amino acid and glucose metabolism. In vitro, combined CAT and PNS restored mitochondrial respiration, rebalanced glycolysis and oxidative phosphorylation, improved glycogen utilization, and upregulated SIRT1 while suppressing HIF-1α in AML12 hepatocytes.

CONCLUSIONS

QTF protects against TW-induced hepatotoxicity, at least in part by modulating the SIRT1/HIF-1α axis, thereby alleviating oxidative stress and restoring hepatic energy and glucose metabolism. These findings provide a mechanistic basis for the detoxifying compatibility of QTF and support safer clinical application of TW-containing formulations.