Du Wanqing, Liang Xiao, Wang Shanze, Lee Philip, Zhang Yunling
Graduate School, Beijing University of Chinese Medicine, Beijing, China.
Department of Neurology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Front Pharmacol. 2020 Nov 23;11:581984. doi: 10.3389/fphar.2020.581984. eCollection 2020.
Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, yet as of currently, there is no disease-modifying therapy that could delay its progression. Pall. is the most frequently used herb in formulas for PD in Traditional Chinese Medicine and also a potential neuroprotective agent for neurodegenerative diseases, while its mechanisms remain poorly understood. In this study, we aim to explore the underlying mechanism of in treating PD utilizing a network pharmacology approach. The protein targets of ingredients and PD were first obtained from several databases. To clarify the key targets, a Protein-Protein-Interaction (PPI) network was constructed and analyzed on the String database, and then enrichment analysis was performed by the Metascape platform to determine the main Gene Ontology biological processes and Kyoto Encyclopedia of Genes and Genomes pathways. Finally, the Ingredient-Target-Pathway (I-T-P) network was constructed and analyzed by Cytoscape software. Six active ingredients of (kaempferol, ß-sitosterol, betulinic acid, palbinone, paeoniflorin and (+)-catechin) as well as six core targets strongly related to PD treatment [AKT1, interleukin-6, CAT, Tumor necrosis factor (TNF), CASP3, and PTGS2] were identified. The main pathways were shown to involve neuroactive ligand-receptor interaction, Calcium signaling pathway, PI3-Akt signaling pathway, TNF signaling pathway, and apoptosis signaling pathway. The main biological process included the regulation of neurotransmitter levels. may retard neurodegeneration by reducing neuroinflammation, inhibiting intrinsic and extrinsic apoptosis, and may improve motor and non-motor symptoms by regulating the levels of neurotransmitters. Our study has revealed the mechanism of in the treatment of PD and may contribute to novel drug development for PD.
帕金森病(PD)是全球第二常见的神经退行性疾病,但截至目前,尚无能够延缓其进展的疾病修饰疗法。 是中医治疗帕金森病方剂中最常用的草药,也是一种潜在的神经退行性疾病神经保护剂,但其作用机制仍知之甚少。在本研究中,我们旨在利用网络药理学方法探索 治疗帕金森病的潜在机制。首先从多个数据库中获取 成分和帕金森病的蛋白质靶点。为了阐明关键靶点,在String数据库上构建并分析了蛋白质-蛋白质相互作用(PPI)网络,然后通过Metascape平台进行富集分析,以确定主要的基因本体生物学过程和京都基因与基因组百科全书通路。最后,通过Cytoscape软件构建并分析成分-靶点-通路(I-T-P)网络。确定了 的六种活性成分(山奈酚、β-谷甾醇、桦木酸、帕宾酮、芍药苷和(+)-儿茶素)以及与帕金森病治疗密切相关的六个核心靶点[AKT1、白细胞介素-6、CAT、肿瘤坏死因子(TNF)、CASP3和PTGS2]。主要通路显示涉及神经活性配体-受体相互作用、钙信号通路、PI3-Akt信号通路、TNF信号通路和凋亡信号通路。主要生物学过程包括神经递质水平的调节。 可能通过减轻神经炎症、抑制内在和外在凋亡来延缓神经退行性变,并可能通过调节神经递质水平来改善运动和非运动症状。我们的研究揭示了 治疗帕金森病的机制,并可能有助于帕金森病新药的开发。