四君子汤治疗帕金森病的作用机制。

IF 2.7 4区 医学 Q3 NEUROSCIENCES Brain Research Pub Date : 2024-12-10 DOI:10.1016/j.brainres.2024.149397
Baoquan Wen , Xiuzhi Li , Jiafu Xu , Yuqin He , Xiaofeng Lin , Xiujuan Wu , Chaoyin Wu
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引用次数: 0

摘要

帕金森病(PD)是第二大最常见的神经退行性疾病,但PD的治疗选择有限,药物开发已达到瓶颈。随着人口老龄化进程的加快,中国PD患者数量日益增多,给患者和社会带来了沉重的负担。因此,从PD的发病机制和疾病靶点出发,探索靶向药物治疗迫在眉睫。古代医生使用中药四君子汤(SJZD)治疗帕金森病。但目前临床上应用较少,其药理机制有待进一步阐明。本研究基于网络药理学研究和分子对接技术,揭示了SJZD治疗PD的机制,表明SJZD提取物作用于细胞微域膜和脂质层,影响泛素-蛋白连接酶结合和泛素样蛋白连接酶结合过程,在神经发生中发挥作用。分子对接结果显示,SJZD中的Ellipticine和Hederagenin对靶点CASP3、BCL2和PTGS2均有显著作用。实验验证了SJZD对MPP+诱导的SH-SY5Y细胞损伤的逆转作用,浓度在5ug/mL ~ 0.1ug/mL范围内,在24 h时表现出明显的细胞保护作用。
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The mechanism of SiJunZi decoction in the treatment of Parkinson’s disease
Parkinson’s disease (PD) is the second most common neurodegenerative disease, but treatment options for PD are limited, and drug development has reached a bottleneck. With the progress of the aging population, the number of PD patients in China is increasing day by day, imposing a heavy burden on patients and society. Therefore, it is urgent to explore targeted medicine based on the pathogenesis of PD and disease targets. Ancient physicians have used the traditional Chinese medicine formula SiJunZi decoction (SJZD) to treat PD. However, it is less commonly used clinically now, and its pharmacological mechanism still needs to be further elucidated. In this study, based on network pharmacology research and molecular docking technology, the mechanism of SJZD in treating PD was revealed, showing that the extract of SJZD acts on cell microdomain membranes and lipid rafts, affecting ubiquitin-protein ligase binding and ubiquitin-like protein ligase binding processes, and plays a role in neurogenesis. Molecular docking results showed that Ellipticine and Hederagenin in SJZD exhibited significant effects on targets: CASP3, BCL2, and PTGS2. The effect of SJZD reversing MPP+-induced SH-SY5Y cells injury was verified by experiments, concentrations ranging from 5ug/mL to 0.1ug/mL showed significant cell protection at 24 h.
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来源期刊
Brain Research
Brain Research 医学-神经科学
CiteScore
5.90
自引率
3.40%
发文量
268
审稿时长
47 days
期刊介绍: An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.
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