triptolide

Triptolide is a diterpenoid epoxide derived from the roots and bark of the Thunder God Vine, Tripterygium wilfordii. It has long been used in traditional Chinese medicine for inflammatory and autoimmune conditions, and in modern research it is studied for potential applications in inflammatory diseases, fibrosis, and cancer. Its potent biological activity is tempered by concerns about toxicity, which limit clinical use in many settings.

Chemically, triptolide is a highly reactive diterpene lactone containing an epoxide group. It is typically isolated from the plant material and used as the core scaffold for research and development of analogs. The compound is notably poorly soluble in water, posing formulation and delivery challenges for therapeutic use.

Biologically, triptolide acts at multiple levels. A central action is inhibition of transcription by targeting the XPB helicase subunit of the transcription factor TFIIH, resulting in reduced RNA polymerase II–dependent transcription. It also suppresses inflammatory mediators such as TNF-α, IL-6, and COX-2, and can inhibit T cell activation and fibrotic processes, with anti-tumor effects observed in various preclinical models. The same potency that drives efficacy also contributes to safety concerns.

Clinical and regulatory aspects: the use of triptolide is limited by significant toxicity, including hepatotoxicity, nephrotoxicity, and reproductive toxicity, along with a narrow therapeutic window. Some derivatives and prodrugs, such as minnelide, are under investigation to improve safety and pharmacokinetics. Regulatory status varies by country; triptolide-containing preparations are generally tightly controlled or limited to traditional medicine contexts under supervision.