Abstract: Objective To propose a hypothesis on the transmission and transformation of organ toxicity by Tripterygium wilfordii based on traditional Chinese medicine (TCM) theories and modern pathophysiological mechanisms in order to contribute to related prevention and control strategies. Methods The clinical manifestations and molecular mechanisms underlying the damage induced by Tripterygium wilfordii to the liver, kidney, heart, gastrointestinal tract and other organs were reviewed. By integrating the Five-element Theory of TCM with modern toxicology, a framework was established to elucidate the mechanisms of such organ toxicity. Results Based on analysis involving Five-element interactions and biological signaling pathways, a time-dependent progression pattern of organ injury was identified, characterized by a dynamic sequence of “originating in the liver (wood), followed by damage to the spleen (earth), heart (fire), and kidney (water), ultimately affecting the lung (metal) and bone marrow”. Such integration suggested that the toxicity of Tripterygium wilfordii did not merely result from isolated organ targeting, but was a networked and sequentially propagated pathological process across organs. Conclusion According to the principle of “blocking disease transmission”, a comprehensive prevention strategy has been proposed that involves early biomarker-based warning systems, rational herb-herb compatibility in TCM formulations for toxicity mitigation, and modern targeted interventions. This integrated framework can not only facilitate safe clinical use of Tripterygium wilfordii, but also provide a reproducible paradigm for investigating organ toxicity in other herbal medicines.

Key words: Tripterygium wilfordii, Organ Toxicity, Five-Element Transmission and Transformation, Inter-Organ Communication, Pharmacovigilance of Traditional Chinese Medicine