Targeting metabolic diseases with celastrol: A comprehensive review of anti-inflammatory mechanisms and therapeutic potential

IF 4.8 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of ethnopharmacology Pub Date : 2025-02-25 DOI:10.1016/j.jep.2025.119560

Xiaojuan Wang , Mohamad Hafizi Abu Bakar , Song Liqun , Mohd Asyraf Kassim , Khairul Anuar Shariff , Thiruventhan Karunakaran

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引用次数: 0

Abstract

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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民族药理学意义：威灵仙是一种用于治疗风湿病的传统中药，具有清热、解毒、祛风、止痛等功效。近年来，其活性化合物青蒿素因其对代谢性疾病的潜在治疗作用而备受关注。塞拉司醇具有调节代谢功能和抗炎作用等生物活性，是治疗肥胖症、糖尿病、动脉粥样硬化（AS）和非酒精性脂肪肝（NAFLD）的理想候选药物：本综述旨在探讨青霉烯醇在代谢性疾病中的药理机制，重点关注其抗炎机制和代谢调节作用，为进一步研究其在代谢性疾病中的治疗潜力提供理论支持：方法：从 PubMed、Web of Science、Scopus、Cochrane 和 Google Scholar 中检索文献。本综述主要集中于青霉烯醇的抗炎机制、代谢调节和毒性研究，系统分析了青霉烯醇在肥胖、糖尿病、强直性脊柱炎和非酒精性脂肪肝中的作用，为其潜在的临床应用提供科学依据：结果：塞拉斯特醇能调节多种信号通路，特别是抑制NF-κB和激活AMPK，减少促炎细胞因子的产生，改善胰岛素敏感性，从而提高其在代谢性疾病中的治疗潜力。此外，玉米甾醇还能通过影响 PPARγ 和 SREBP-1c 等关键转录因子来调节脂肪生成和能量代谢。大量研究强调了其在缓解氧化应激和改善线粒体功能方面的作用，从而进一步提高了其在代谢方面的益处：总之，作为一种治疗代谢疾病的多靶点药物，青霉烯醇具有抗炎、调节代谢和抗氧化的功效，前景广阔。尽管如此，由于其生物利用率低和潜在毒性，芹菜醇的临床应用仍面临挑战。迫切需要先进的制剂策略和靶向给药系统来克服生物利用度和临床转化方面的挑战。

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来源期刊

Journal of ethnopharmacology 医学-全科医学与补充医学

CiteScore

10.30

自引率

5.60%

发文量

967

审稿时长

77 days

期刊介绍： The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.