Abstract
The identification of new bioactive compounds derived from medicinal plants with significant therapeutic properties has attracted considerable interest in recent years. Such is the case of the Tripterygium wilfordii (TW), an herb used in Chinese medicine. Clinical trials performed so far using its root extracts have shown impressive therapeutic properties but also revealed substantial gastrointestinal side effects. The most promising bioactive compound obtained from TW is celastrol. During the last decade, an increasing number of studies were published highlighting the medicinal usefulness of celastrol in diverse clinical areas. Here we systematically review the mechanism of action and the therapeutic properties of celastrol in inflammatory diseases, namely, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases, osteoarthritis and allergy, as well as in cancer, neurodegenerative disorders and other diseases, such as diabetes, obesity, atherosclerosis, and hearing loss. We will also focus in the toxicological profile and limitations of celastrol formulation, namely, solubility, bioavailability, and dosage issues that still limit its further clinical application and usefulness.
Highlights
The identification of bioactive compounds derived from medicinal plants has attracted considerable interest in recent years for their strong and in some cases unique, anti-inflammatory, anticancer, and neuroprotective properties
Astry and colleagues have described, in synovium-infiltrating cells (SIC) from adjuvant-induced arthritis (AIA) rats, that celastrol reduces Th17 and increases T regulatory (Treg) cell frequencies, possibly favoring an anti-inflammatory/immunomodulatory local environment in the inflamed joints [46]. It inhibits Th17 and promotes Treg differentiation through the decrease of pSTAT3 as well as of IL-1β and IL-6 production [46]. These data, together with our results showing that celastrol is more effective than Digoxin in suppressing arthritis in AIA model [39], suggest that the combined effect of celastrol in both Th17 and Treg cells is an advantage in the treatment of arthritis
Cathepsin k (Ctsk)) and in transcriptional factors (c-Fos, c-Jun, and nuclear factor of activated T-cells 1 (NFATc1)), possibly due to nuclear factor kappa B (NF-kB) and mitogen-activated protein kinase (MAPK) inhibition [49]. These results suggest that celastrol acts both downstream of receptor activator of nuclear factor kappa-B ligand (RANKL) at the levels of NF-kB activation and upstream targeting proinflammatory cytokine signaling
Summary
The identification of new bioactive compounds derived from medicinal plants with significant therapeutic properties has attracted considerable interest in recent years. Such is the case of the Tripterygium wilfordii (TW), an herb used in Chinese medicine.
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