Triptolide: A Review of Its Traditional Use, Derivatives, Pharmacology, Antitumor Effect, and Clinical Applications

Triptolide (TPL), a diterpenoid derived from the Chinese medicinal plant Tripterygium wilfordii, exhibits broad-spectrum biological and pharmacological activities, although its clinical translation is limited by systemic toxicity. Recent advances in the development of TPL derivatives have created new therapeutic opportunities. This review summarizes current knowledge of triptolide, with a focus on TPL’s toxicity profile, derivative strategies, and antitumor mechanisms. There are at least ten cancer types studied by research. We also summary the plant origin and traditional uses of the plant, TPL’s pharmacokinetics (PK), and relevant clinical trials against tumors. The main mechanism of TPL antitumor effect is interfere ATPase of XPB via covalently binding to it, as well as inducing rapid depletion of RPB1 via hyperphosphorylation and ubiquitination. We also reviewed systematic toxicity including neuro, cardio, oto, nephron, hepato, digestive hemato and reproductive toxicity. Finally, we searched the clinical trials through three platforms against tumor and concluded that Minnelide has great potential against solid tumor in clinic. By critically evaluating TPL and its derivatives from multiple dimensions, this review aims to inform future strategies that maximize therapeutic efficacy while minimizing adverse effects.