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Potential medicinal value of celastrol and its synthesized analogues for central nervous system diseases

雷公藤醇 中枢神经系统 神经炎症 医学 药理学 神经保护 疾病 雷公藤 神经系统 生物 内科学 病理 精神科 细胞凋亡 生物化学 替代医学
作者
Xue Bai,Rui‐Jia Fu,Shuo Zhang,Shi‐Jun Yue,Yan‐Yan Chen,Ding‐Qiao Xu,Yuping Tang
出处
期刊:Biomedicine & Pharmacotherapy [Elsevier]
卷期号:139: 111551-111551 被引量:23
标识
DOI:10.1016/j.biopha.2021.111551
摘要

The central nervous system (CNS) is a vital part of the human nervous system, and the incidence of CNS disease is increasing year by year, which has become a major public health problem and a prominent social problem. At present, the drugs most commonly used in the clinic are receptor regulators, and neurotransmitter inhibitors, but they are accompanied by serious side effects. Therefore, the identification of new drugs and treatment strategies for CNS disease has been a research hotspot in the medical field. Celastrol, a highly bio-active pentacyclic triterpenoid isolated from Tripterygium wilfordii Hook. F, has been proved to have a wide range of pharmacological effects, such as anti-inflammation, immunosuppression, anti-obesity and anti-tumor activity. However, due to its poor water solubility, low bioavailability and toxicity, the clinical development and trials of celastrol have been postponed. However, in recent years, the extensive medical value of celastrol in the treatment of CNS diseases such as nervous system tumors, Alzheimer's disease, Parkinson's disease, cerebral ischemia, multiple sclerosis, spinal cord injury, and amyotrophic lateral sclerosis has gradually attracted intensive attention worldwide. In particular, celastrol has non-negligible anti-tumor efficacy, and as there are no 100% effective anti-tumor drugs, the study of its structural modification to obtain better leading compounds with higher efficiency and lower toxicity has aroused strong interest in pharmaceutical chemists. In this review, research progress on celastrol in CNS diseases and the synthesis of celastrol-type triterpenoid analogues and their application evaluation in disease models, such as CNS diseases and autotoxicity-related target organ cancers in the past decade are summarized in detail, in order to provide reference for future better application in the treatment of CNS diseases.
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