巴兰球茎草对脂多糖诱导RAW264.7细胞的抗炎机制:基于网络药理学和分子对接的分析和验证。
[Anti-inflammatory mechanism of Balanophora involucrata: a network pharmacology and molecular docking-based analysis and verification in lipopolysaccharide-induced RAW264.7 cells].
发表日期:2023 Mar 20
作者:
Y Zhang, X Tu, Y Zhang, D Wen, F Zhao, L Yuan, W Li
来源:
Cellular & Molecular Immunology
摘要:
基于网络药理学和分子对接技术,研究蛇菰化学成分及其抗炎机制。检索文献报道、中药材、GeneCards等数据库中的抗炎化合物及其靶标。使用String数据库和Cytoscape 3.7.2软件获得蛋白质相互作用(PPI)网络和药物-活性成分-靶标网络并进行GO和KEGG富集分析。使用Auto Dock Tools 1.5.6进行分子对接。在脂多糖(LPS)诱导的RAW264.7炎症细胞模型中,使用ELISA和Western blotting检测25、50、100和200μg/mL蛇菰提取物对炎症细胞因子的产生和PI3K和Akt的磷酸化水平的影响。共鉴定了318个通用的药物和疾病靶标,核心靶标包括Src、HSP90AA1和PIK3CA,涉及癌症、PI3K/Akt、MAPK和其他信号通路,KEGG分析表明。分子对接显示,蛇菰化学成分可以自发地结合到核心靶标上。在炎症细胞模型中,使用蛇菰提取物治疗,100和200μg/mL浓度明显抑制了IL-1β的产生,并在50、100和200μg/mL浓度下降低了IL-6和TNF-α的表达水平,在25、50、100和200μg/mL浓度下降低了PI3K和Akt蛋白的磷酸化水平(所有P<0.05)。蛇菰的抗炎机制涉及多靶点和多途径,其作用可能通过降低IL-1β、IL-6和TNF-α的产生,抑制PI3K和Akt蛋白的磷酸化水平从而抑制PI3K/Akt信号通路的激活来介导。
To investigate the main chemical constituents of Balanophora involucrata and the mechanism of its antiinflammatory effect based on network pharmacology and molecular docking technology.Literature reports, Materia Medica, GeneCards and other databases were searched for anti-inflammatory compounds and their targets. String database and Cytoscape 3.7.2 software were used to obtain the protein-protein interaction (PPI) network and the drug-active ingredienttargets network and for GO and KEGG enrichment analyses. Molecular docking was performed using Auto Dock Tools 1.5.6. In an inflammatory RAW264.7 cell model induced by lipopolysaccharide (LPS), the effect of 25, 50, 100, 200 μg/mL Balanophora involucrata extract was tested on the production of inflammatory cytokines and phosphorylation level of PI3K and Akt using ELISA and Western blotting.A total of 318 common targets of drugs and diseases were identified, and the core targets were Src, HSP90AA1 and PIK3CA, involving cancer, PI3K/Akt, MAPK and other signaling pathways as shown by KEGG analysis. Molecular docking showed that both the main active constituents of Balanophora involucrata could spontaneously bind to the core targets. In the inflammatory cell model, treatment with Balanophora involucrata extract significantly inhibited the production of IL-1β at the concentrations of 100 and 200 μg/mL, reduced IL-6 and TNF-α expressions at the concentrations of 50, 100, and 200 μg/mL, and lowered phosphorylation levels of PI3K and Akt proteins at the concentrations of 25, 50, 100, and 200 μg/mL (all P < 0.05).The anti-inflammatory mechanism of Balanophora involucrata involves multiple targets and multiple pathways, and its effect is mediated possibly by reducing IL-1β, IL-6 and TNF-α production and inhibiting phosphorylation levels of PI3K and Akt proteins to suppress the activation of the PI3K/Akt signaling pathway.