Therapeutic Effects and Related Molecular Mechanisms of Celastrol, a Triterpenoid Natural Compound and Novel HSP90 Inhibitor Extracted from Plants of the Celastraceae Family

Celastrol, a triterpenoid compound first identified in the Chinese herbal Tripterygium Wilfordii Hook, f. (TWHF), has attracted much attention in recent years due to its promise in multiple applications. Initially, celastrol was studied mainly as a toxic agent to treat cancer and inflammation. Celastrol’s potential applications have since expanded following findings that it could protect cells due to inducing heat shock proteins via HSF-1 activation (now attributed as caused by HSP90 inhibition). In this paper, we review the therapeutic effects of celastrol towards a variety of abnormalities demonstrated in animal models, including autoimmune and inflammatory diseases, various cancers, neurodegenerative issues, and chronic metabolic disorders. The cellular responses, signaling pathways and proteins reportedly affected by celastrol are also introduced. Moreover, based on celastrol’s chemical structure and properties, as well as reported findings, we present a new molecular model for celastrol’s direct inhibition of the HSP90 chaperone complex, which might be generalized to cover the interactions between celastrol and other targeted proteins. Finally, we suggest future work focusing on clinical translation.