Abstract
Celastrol, a triterpenoid derived from traditional Chinese medicinal plants, has anti-inflammatory, antioxidant, and anticancer activities. Celastrol has shown preventive/therapeutic effects in experimental models of several chronic diseases. These include, chronic inflammatory and autoimmune diseases (e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease, and psoriasis), neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis), atherosclerosis, obesity, Type 2 diabetes, and cancer. Celastrol modulates intricate cellular pathways and networks associated with disease pathology, and it interrupts or redirects the aberrant cellular and molecular events so as to limit disease progression and facilitate recovery, where feasible. The major cell signaling pathways modulated by celastrol include the NF-kB pathway, MAPK pathway, JAK/STAT pathway, PI3K/Akt/mTOR pathway, and antioxidant defense mechanisms. Furthermore, celastrol modulates cell proliferation, apoptosis, proteasome activity, heat-shock protein response, innate and adaptive immune responses, angiogenesis, and bone remodeling. Current understanding of the mechanisms of action of celastrol and information about its disease-modulating activities in experimental models have set the stage for testing celastrol in clinical studies as a therapeutic agent for several chronic human diseases.