The conversion of evodiamine-induced hepatotoxicity into a therapeutic effect on colonitis: insight from the liver-gut axis mediated by PPAR/NF-κB/ZO-1/caspase-3 pathway

The hepatotoxicity observed under healthy conditions and the therapeutic efficacy of EVO against UC are both associated with EVO's modulation of the PPAR/NF-κB/ZO-1/caspase-3 pathway. The influence of EVO on the expression of these key proteins within the gut-liver axis may be modulated by distinct physiological states, resulting in either antagonistic or synergistic effects that potentially lead to differential biological responses across multiple organs. This study not only provides essential supplementation and refinement to the understanding of EVO-induced hepatotoxicity but also identifies a novel breakthrough in accurately assessing its liver toxicity. Specifically, the evaluation of EVO's hepatotoxic potential should be grounded in the principles of TCM and aligned with its clinical application characteristics. Furthermore, these findings offer valuable insights for the safety assessment and development of traditional Chinese medicines with potential hepatotoxic risks.