Celastrol

Celastrol is a natural pentacyclic triterpenoid isolated from Tripterygium wilfordii, also called the Thunder God Vine. It has attracted interest for anti-inflammatory, immunomodulatory and anti-cancer properties observed in preclinical studies.

Chemically, celastrol contains a reactive quinone methide–type moiety, contributing to its electrophilic reactivity with thiol groups in proteins. It is highly lipophilic, with poor water solubility, leading to limited oral bioavailability in many settings.

Biological activity: Celastrol inhibits NF-κB signaling and modulates JAK/STAT and MAPK pathways; it can activate the cellular heat shock response through HSF1, increasing expression of heat shock proteins such as HSP70. It may also affect proteasome activity and can covalently modify cysteine residues in target proteins via its electrophilic center.

In preclinical models, celastrol reduces inflammatory cytokine production, exerts anti-tumor effects in various cancer cell lines, and has been explored in obesity and metabolic disorder models.

Safety and regulatory status: Celastrol carries substantial toxicity risks observed in animal studies, including hepatotoxicity and nephrotoxicity, and its therapeutic window is narrow. Owing to solubility and safety concerns, it is not approved for clinical use and is studied mainly as a research tool or in traditional medicine contexts with caution.