Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, Shaanxi Province, China.
School of Clinical Medicine (Guang'anmen Hospital), Beijing University of Chinese Medicine, Beijing 100029, China.
Biomed Pharmacother. 2021 Jul;139:111551. doi: 10.1016/j.biopha.2021.111551. Epub 2021 Apr 14.
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.
中枢神经系统（CNS）是人体神经系统的重要组成部分，CNS 疾病的发病率逐年上升，已成为重大的公共卫生问题和突出的社会问题。目前，临床上最常用的药物是受体调节剂和神经递质抑制剂，但它们伴随着严重的副作用。因此，寻找治疗 CNS 疾病的新药和治疗策略一直是医学领域的研究热点。从雷公藤中分离得到的高度生物活性的五环三萜化合物雷公藤红素已被证明具有广泛的药理作用，如抗炎、免疫抑制、抗肥胖和抗肿瘤活性。然而，由于其水溶性差、生物利用度低和毒性，雷公藤红素的临床开发和试验已经被推迟。然而，近年来，雷公藤红素在治疗 CNS 疾病（如神经系统肿瘤、阿尔茨海默病、帕金森病、脑缺血、多发性硬化症、脊髓损伤和肌萎缩侧索硬化症）方面的广泛医学价值逐渐引起了全球的关注。特别是，雷公藤红素具有不可忽视的抗肿瘤功效，而且由于没有 100%有效的抗肿瘤药物，因此研究其结构修饰以获得更高效率和更低毒性的更好先导化合物引起了药物化学家的浓厚兴趣。在本文中，详细总结了过去十年中雷公藤红素在 CNS 疾病中的研究进展以及雷公藤红素型三萜类化合物类似物的合成及其在 CNS 疾病和自毒性相关靶器官癌症等疾病模型中的应用评价，以期为未来更好地应用于 CNS 疾病的治疗提供参考。
