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  1. Wang X, Abu Bakar MH, Liqun S, Kassim MA, Shariff KA, Karunakaran T
    J Ethnopharmacol, 2025 Mar 26;344:119560.
    PMID: 40015541 DOI: 10.1016/j.jep.2025.119560
    ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium wilfordii is a traditional Chinese medicine used to treat rheumatic diseases, with properties such as clearing heat, detoxifying, dispelling wind, and relieving pain. In recent years, its active compound, celastrol, garnered significant attention for its potential therapeutic effects on metabolic diseases. Celastrol exhibits bioactivities such as regulating metabolic functions and anti-inflammatory effects, positioning it as a promising candidate for the treatment of obesity, diabetes, atherosclerosis (AS), and non-alcoholic fatty liver disease (NAFLD).

    AIM OF THE REVIEW: This review aims to explore the pharmacological mechanisms of celastrol in metabolic diseases, focusing on its anti-inflammatory mechanisms and metabolic regulation effects, providing theoretical support for further investigation of its therapeutic potential in metabolic diseases.

    METHODS: Literature was retrieved from PubMed, Web of Science, Scopus, Cochrane, and Google Scholar. This review primarily focuses on anti-inflammatory mechanisms of celastrol, its metabolic regulation, and toxicity studies, by systematically analyzing its effects in obesity, diabetes, AS, and NAFLD, providing scientific evidence for its potential clinical applications.

    RESULTS: Celastrol regulates multiple signaling pathways, particularly inhibiting NF-κB and activating AMPK, reducing the production of pro-inflammatory cytokines and improving insulin sensitivity, enhancing its therapeutic potential in metabolic diseases. Additionally, celastrol regulates adipogenesis and energy metabolism by influencing key transcription factors such as PPARγ and SREBP-1c. Numerous studies highlight its role in alleviating oxidative stress and improving mitochondrial function, further enhancing its metabolic benefits.

    CONCLUSION: In summary, celastrol holds great promise as a multi-target therapeutic agent for metabolic diseases, offering anti-inflammatory, metabolic regulatory, and antioxidative benefits. Despite these, challenges remain for the clinical application of celastrol due to its poor bioavailability and potential toxicity. Advanced formulation strategies and targeted delivery systems are urgently needed to overcome challenges related to bioavailability and clinical translation.

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