[Efficacy-toxicity duality of Tripterygium wilfordii in treatment of rheumatic and immune diseases: mechanisms, strategies for toxicity attenuation and efficacy enhancement, and future perspectives].

Rheumatic and immune diseases constitute a major global disease burden. Tripterygium wilfordii demonstrates remarkable therapeutic efficacy in treating rheumatoid arthritis, systemic lupus erythematosus and related conditions. However, its prominent hepatic, renal, and reproductive toxicities engender a characteristic "efficacy-toxicity duality", thereby limiting its broader clinical adoption and safe application. This study systematically synthesized domestic and international research over the past two decades to construct a regulatory network governing the "efficacy-toxicity duality" of T. wilfordii from an integrative "component-pathway-spatiotemporal-host(individual)" perspective. It dissected the underlying mechanisms linking efficacy and toxicity, elucidating that key constituents such as triptolide exert dual effects through intervention in shared signaling pathways, including nuclear factor erythroid 2-related factor 2(Nrf2) and signal transducer and activator of transcription 3(STAT3), where the specific outcome of efficacy versus toxicity is dictated by defined "dose-time" windows, tissue distribution patterns, and individual host factors. The study further reviewed toxicity attenuation and efficacy enhancement strategies, including structural modification, targeted delivery, and combination pharmacotherapy. In response to three translational bottlenecks-inconsistent quality, inefficient delivery, and lagging evaluation-this work proposed the establishment of end-to-end quality control standards, the development of intelligent responsive delivery systems, and the integration of emerging technologies such as artificial intelligence and organoids into an advanced "efficacy-toxicity" evaluation framework. Collectively, these efforts aim to provide an integrative theoretical framework and translatable innovation pathways for advancing T. wilfordii toward safe, controllable, and precision-oriented modern pharmaceuticals, thereby facilitating the modernization of traditional Chinese medicine and its global clinical dissemination.