Zunyi Medical University, College of Basic Medicine, Zunyi, Guizhou, China.
Medicine (Baltimore). 2023 Oct 27;102(43):e35669. doi: 10.1097/MD.0000000000035669.
Neurotoxicity could be induced by long exposure to manganese (Mn). The traditional Chinese medicine, Corididius chinensis (Cc) has been proven to have a certain curative effect on Mn poisoning. Therefore, network pharmacology was performed to explore potential therapeutic targets and pharmacological mechanisms of Cc. We found ingredients by building our own database through literature, (which is the first to screen traditional Chinese medicine without traditional Chinese medicine systems pharmacology database and analysis platform databases and it is applicable whenever a Chinese medicine is not found in the traditional Chinese medicine systems pharmacology database and analysis platform database) and potential targets of Mn-induced nervous system diseases from the OMIM, GeneCards, and DrugBank database were identified. A protein-protein interaction network was constructed using Cytoscape. Gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analysis was performed for the treatment of Mn-induced nervous system disease, and molecular docking was carried out to verify the results of network pharmacology analysis. After screening disease-related genes, 12 intersecting genes overlapped between 284 target proteins of the active compound and 195 potential disease targets. The pathways of neurodegeneration_multiple diseases and Alzheimer disease pathway may be the most potential pathway of Cc treating Mn-induced nervous system diseases. CASP9 and PTGS2 in neurodegeneration_multiple diseases, NOS1, NOS2 in Alzheimer disease pathway were identified as core targets. Especially, molecule docking analysis unveil that aspongpyrazine A docking NOS2 is the most potential therapeutic drug and target, which primarily involved in the processes of oxidative stress and inflammation.
长期暴露于锰（Mn）可导致神经毒性。已证实中药川牛膝（Cc）对锰中毒具有一定的疗效。因此，采用网络药理学方法探索 Cc 的潜在治疗靶点和药理机制。我们通过文献构建了自己的数据库，从中筛选出成分（这是首次筛选传统中药，不依赖于中药系统药理学数据库和分析平台数据库，适用于中药系统药理学数据库和分析平台数据库中未发现的中药），并从 OMIM、GeneCards 和 DrugBank 数据库中确定了 Mn 诱导的神经系统疾病的潜在靶点。使用 Cytoscape 构建蛋白质-蛋白质相互作用网络。对 Mn 诱导的神经系统疾病的治疗进行基因本体和京都基因与基因组百科全书通路富集分析，并进行分子对接验证网络药理学分析的结果。筛选疾病相关基因后，在活性化合物的 284 个靶蛋白和 195 个潜在疾病靶标之间有 12 个重叠的交集基因。神经退行性疾病多疾病和阿尔茨海默病途径可能是 Cc 治疗 Mn 诱导的神经系统疾病最有潜力的途径。神经退行性疾病多疾病中的 CASP9 和 PTGS2 以及阿尔茨海默病途径中的 NOS1 和 NOS2 被确定为核心靶点。特别是，分子对接分析揭示了 aspongpyrazine A 对接 NOS2 是最有潜力的治疗药物和靶点，主要涉及氧化应激和炎症过程。
