■在中医中,川芎。(LCH)用于治疗神经性疼痛(NP)。进行这项研究是为了研究潜在的药理机制。
■LCH的主要成分是从TCMSP数据库获得的。使用瑞士目标预测数据库和HERB数据库获得活性组分的目标。从CTD数据库和GeneCard数据库获得NP相关基因。使用STRING平台和Cytoscape3.9.0软件构建蛋白质-蛋白质相互作用(PPI)网络。使用DAVID数据库进行GO和KEGG富集分析。使用分子对接和分子动力学模拟验证了关键成分与hub靶蛋白之间的相互作用。此外,使用100ng/mL脂多糖(LPS)诱导小胶质细胞系HMC3极化为M1表型。定量实时聚合酶链反应(qRT-PCR),Westernblot和酶联免疫吸附试验检测M1标志物和炎症因子的表达水平,分别。
■确定了LCH的七个LCH活性成分,对应于387个靶基因。获得2019个NP相关基因,总共174个NP相关基因被鉴定为可被LCH调节的靶基因。β-谷甾醇,senkyunone,wallichilide,Myricanone,在NP的治疗中,甘露糖醇被认为是LCH的关键成分。SRC,BCL2、AKT1、HIF1A和HSP90AA1被鉴定为hub靶蛋白。GO分析表明,328个生物过程,61个细胞组件,85个分子功能可能是由LCH的成分调节的,和KEGG富集分析表明,132条信号通路可能受到LCH成分的调节。β-谷甾醇,senkyunone,wallichilide,Myricanone,和甘露糖醇与包括SRC在内的hub靶蛋白显示出良好的结合活性,BCL2、AKT1和HSP90AA1。此外,β-谷甾醇在体外抑制LPS诱导的HMC3中的M1极化。
■本研究为LCH在多组分处理NP中的应用提供了理论依据,多目标,和多种途径。
UNASSIGNED: In traditional Chinese medicine, Ligusticum chuanxiong Hort. (LCH) is used to treat neuropathic pain (NP). This
study was performed to investigate the underlying pharmacological mechanisms.
UNASSIGNED: The main components of the LCH were obtained from the TCMSP database. The targets of the active components were obtained using the Swiss Target Prediction database and HERB database. The NP-related genes were obtained from the CTD database and GeneCard database. Protein-protein interaction (PPI) network was constructed using the STRING platform and Cytoscape 3.9.0 software. GO and KEGG enrichment analyses were performed using the DAVID database. Interactions between the key components and hub target proteins were verified using molecular docking and molecular dynamics simulation. In addition, microglial cell line HMC3 was induced to polarize to the M1 phenotype using 100 ng/mL lipopolysaccharide (LPS). Quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and enzyme-linked immunosorbent assays were used to detect the expression levels of M1 markers and inflammatory factors, respectively.
UNASSIGNED: Seven LCH active components of LCH were identified, corresponding to 387 target genes. 2019 NP-related genes were obtained, and a total of 174 NP-related genes were identified as target genes that could be modulated by LCH. Beta-sitosterol, senkyunone, wallichilide, myricanone, and mandenol were considered as the key components of LCH in the treatment of NP. SRC, BCL2, AKT1, HIF1A and HSP90AA1 were identified as the hub target proteins. GO analysis showed that 328 biological processes, 61 cell components, and 85 molecular functions were likely modulated by the components of LCH, and KEGG enrichment analysis showed that 132 signaling pathways were likely modulated by the components of LCH. Beta-sitosterol, senkyunone, wallichilide, myricanone, and mandenol showed good binding activity with hub target proteins including SRC, BCL2, AKT1, and HSP90AA1. In addition, beta-sitosterol inhibited LPS-induced M1 polarization in HMC3 in vitro.
UNASSIGNED: This
study provides a theoretical basis for the application of LCH in the treatment of NP through multicomponent, multitarget, and multiple pathways.