Liu Zhihua, Zhao Jiahao, Yang Shuyuan, Zhang Yu, Song Lu, Wu Na, Liu Zhenguo
Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Nutr. 2022 May 6;9:836500. doi: 10.3389/fnut.2022.836500. eCollection 2022.
Parkinson's disease (PD) is the second most common neurodegenerative disease. Tianqi Pingchan Granule (TPG) is a clinically effective formula of traditional Chinese medicine to treat PD. However, the therapeutic effect and underlying mechanisms of TPG in PD remain unclear. Based on network pharmacology, the corresponding targets of TPG were identified using the Traditional Chinese Medicine Database and Analysis Platform Database. Differentially expressed genes in PD were obtained from the Therapeutic Target Database, Online Mendelian Inheritance in Man, GeneCards, and DrugBank databases. The protein-protein interaction (PPI) networks of intersected targets were constructed using the STRING database and visualized using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and the pathways directly related to the pathogenesis of PD were integrated manually. Furthermore, studies were carried out based on network pharmacology. The gut microbiota, peripheral inflammatory cytokines, and glia-mediated neuroinflammation in substantia nigra were evaluated. A total of 99 target genes were intersected between targets of TPG and deferentially expressed genes in PD. The PPI network analysis indicated the proinflammatory cytokine as essential targets. GO and KEGG analyses indicated that inflammatory response and its related signaling pathways were closely associated with TPG-mediated PD treatment. studies revealed that class Negativicutes and order Selenomonadales decreased, whereas class Mollicutes, order Enterobacteriales, and Mycoplasmatales increased in fecal samples of PD rats 16S rRNA sequence analysis. Furthermore, the function prediction methods purposely revealed that TPG therapy may be involved in flavonoid biosynthesis, which have anti-inflammatory properties. In addition, studies revealed that TPG exposure was found to not only attenuate the production of peripheral inflammatory cytokines but also inhibit the activation of microglia and astrocytes in substantia nigra of PD rats. Through network pharmacology and experiment-combined approach, the mechanisms of TPG in the treatment of PD were revealed, and the role of TPG in the regulation of gut microbiota and inflammatory response was confirmed.
帕金森病（PD）是第二常见的神经退行性疾病。天芪平颤颗粒（TPG）是治疗PD的一种临床有效的中药方剂。然而，TPG治疗PD的疗效及潜在机制仍不清楚。基于网络药理学，利用中药数据库及分析平台数据库确定TPG的相应靶点。从治疗靶点数据库、人类孟德尔遗传在线数据库、基因卡片数据库和药物银行数据库中获取PD中的差异表达基因。使用STRING数据库构建相交靶点的蛋白质-蛋白质相互作用（PPI）网络，并使用Cytoscape进行可视化。进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析，并手动整合与PD发病机制直接相关的通路。此外，基于网络药理学开展了研究。评估了肠道微生物群、外周炎性细胞因子以及黑质中胶质细胞介导的神经炎症。TPG的靶点与PD中的差异表达基因共有99个相交的靶基因。PPI网络分析表明促炎细胞因子是关键靶点。GO和KEGG分析表明炎症反应及其相关信号通路与TPG介导的PD治疗密切相关。研究显示，通过16S rRNA序列分析，PD大鼠粪便样本中Negativicutes菌纲和Selenomonadales目减少，而Mollicutes菌纲、肠杆菌目和支原体目增加。此外，功能预测方法特意显示TPG治疗可能参与具有抗炎特性的类黄酮生物合成。另外，研究显示TPG不仅能减少外周炎性细胞因子的产生，还能抑制PD大鼠黑质中小胶质细胞和星形胶质细胞的激活。通过网络药理学与实验相结合的方法，揭示了TPG治疗PD的机制，并证实了TPG在调节肠道微生物群和炎症反应中的作用。
