title: Molecular targets of celastrol derived from Thunder of God Vine: potential role in the treatment of inflammatory disorders and cancer.
abstract: Identification of active constituents and their molecular targets from traditional medicine is an enormous opportunity for modern pharmacology. Celastrol is one such compound that was originally identified from traditional Chinese medicine (Thunder of God Vine) almost three decades ago and generally used for the treatment of inflammatory and auto-immune diseases. Celastrol has attracted great interest recently, especially for its potential anti-inflammatory and anti-cancer activities. The anti-inflammatory effects of this triterpene have been demonstrated in animal models of different inflammatory diseases, including arthritis, Alzheimer's disease, asthma, and systemic lupus erythematosus. This triterpene has also been found to inhibit the proliferation of a variety of tumor cells and suppress tumor initiation, promotion and metastasis in various cancer models in vivo. Celastrol's ability to modulate the expression of pro-inflammatory cytokines, MHC II, HO-1, iNOS, NF-κB, Notch-1, AKT/mTOR, CXCR4, TRAIL receptors DR4 and DR5, CHOP, JNK, VEGF, adhesion molecules, proteasome activity, topoisomerase II, potassium channels, and heat shock response has been reported. This review describes the various molecular targets of celastrol, cellular responses to celastrol, and animal studies with celastrol in cancer and other inflammatory disorders.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Radhamani
authors.initials: R
authors.lastname: Kannaiyan
authors.forename: Muthu K
authors.initials: MK
authors.lastname: Shanmugam
authors.forename: Gautam
authors.initials: G
authors.lastname: Sethi
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D009369:Neoplasms / Q000188:drug therapy*; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D029757:Tripterygium / Q000737:chemistry*; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts; D014315:Triterpenes; C050414:celastrol