Molecular mechanisms and delivery strategies of celastrol targeting inflammation-associated autoimmune diseases

Tripterygium wilfordii Hook.f. (TwHF), a traditional Chinese medicine recorded in the Compendium of Materia Medica, has been used to treat inflammation and rheumatic diseases. Celastrol, a pentacyclic triterpenoid derived from TwHF, exhibits potent anti-inflammatory and immunomodulatory properties, showing promise for autoimmune diseases (ADs). However, its clinical application has been hindered by poor bioavailability and toxicity.

The paper aims to systematically analyze the molecular mechanisms by which celastrol treats inflammation-related ADs and evaluates novel delivery strategies to overcome its druggability limitations.

The research information on celastrol was obtained from Google Scholar, PubMed, Web of Science, and SciFinder.

Celastrol ameliorates rheumatoid arthritis (RA), psoriasis (PS), multiple sclerosis (MS), and systemic lupus erythematosus (SLE) through multi-target mechanisms, including modulation of key transcription factors, immune cell functions, and autophagy pathways. Nanomaterial-based delivery systems have improved its targeting, sustained release, and safety profile.

Celastrol has considerable therapeutic potential for ADs via pleiotropic anti-inflammatory actions. Advanced delivery systems address critical barriers to clinical application. Future research should integrate spatial metabolomics, AI-assisted design, and interdisciplinary approaches to facilitate its clinical adoption.