Immunomodulatory Effects of Tripterygium wilfordii in Diabetes: Mechanisms and Therapeutic

Background and Objectives: To systematically evaluate the therapeutic potential and underlying mechanisms of Tripterygium wilfordii Hook F. (TwHF) and its active constituents, particularly celastrol and triptolide, in autoimmune and metabolic disorders, with a focus on diabetes and its complications. Materials and Methods: A comprehensive review of recent preclinical and clinical studies was conducted, highlighting the pharmacological effects of TwHF in autoimmune diseases such as rheumatoid arthritis and psoriasis, as well as its emerging applications in metabolic conditions like diabetes. Mechanistic insights were drawn from molecular and cellular studies, and clinical data were summarized to assess efficacy and safety. Results: TwHF exhibits multi-target immunomodulatory effects. Celastrol was found to improve insulin resistance by modulating the carbohydrate response element-binding protein (ChREBP)–thioredoxin-interacting protein (TXNIP) axis and to alleviate diabetic complications by inhibiting inflammatory pathways, including nuclear factor-κB (NF-κB) and mitogenactivated protein kinase (MAPK). Clinical trials have shown that TwHF extracts significantly reduce proteinuria in diabetic nephropathy patients. However, potential toxicity remains a concern and limits broader clinical application. Conclusion: T. wilfordii and its key constituents hold promise as therapeutic agents for autoimmune and metabolic diseases due to their potent immunoregulatory properties. Further research is needed to optimize efficacy and safety, particularly for long-term use in diabetes-related conditions.