艾叶黄酮类化合物柚皮苷和槲皮素通过抑制白细胞介素-1β（IL-1β）/基质金属蛋白酶 9（MMP9）抗动脉粥样硬化作用的网络药理学分析及验证。
Anti-atherosclerotic effects of naringenin and quercetin from Folium Artemisiae argyi by attenuating Interleukin-1 beta (IL-1β)/ matrix metalloproteinase 9 (MMP9): network pharmacology-based analysis and validation.
机构信息
Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization, Huanggang Normal University, Huanggang, 438000, China.
Hubei Collaborative Innovation Center for the Characteristic Resources Exploitation of Dabie Mountains, Huanggang Normal University, Huanggang, 438000, China.
出版信息
BMC Complement Med Ther. 2023 Oct 25;23(1):378. doi: 10.1186/s12906-023-04223-1.
Effective components and related target genes of Folium Artemisiae argyi were screened from Traditional Chinese Medicines for Systems Pharmacology Database and Analysis Platform. The therapeutic targets of atherosclerosis were searched in the MalaCards and OMIM databases. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed in WebGestalt online and verified according to ClueGo and Pedia apps in Cytoscape. Then, the protein-protein interaction network was analyzed using the STRING database and constructed using Cytoscape. Differential expression of target genes was identified in GSE9128 and GSE71226 by GEO2R. And then, molecular docking was performed using the Molecular Operating Environment. Finally, we validated the protein expression of Interleukin-6 (IL-6)/IL-1β /MMP9 by qRT-PCR and Western blot in Raw264.7 which was induced by LPS. A total of 232 potential target genes and 8 ingredients of Folium Artemisiae argyi were identified. Quercetin and naringenin are potential candidate bioactive agents in treating atherosclerosis. Vascular endothelial growth factor (VEGFA), MMP9 and IL-1β could be potential target genes. KEGG analysis demonstrated that the fluid shear stress and atherosclerosis pathway play a crucial role in the anti-atherosclerosis effect of Folium Artemisiae argyi. Gene Expression Omnibus (GEO) validation demonstrated that VEGFA was downregulated, while MMP9 and IL-1β were upregulated in patients with atherosclerosis. Molecular docking suggested that only MMP9 had a good combination with quercetin. The cell experiment results suggested that naringenin and quercetin have strong anti-inflammation effects, and significantly inhibit the expression of MMP9. Practical ApplicationsArtemisiae argyi is a traditional Chinese herbal medicine that has been widely used for its antibacterial and anti-inflammatory effects. This research demonstrated the bioactive ingredients, potential targets, and molecular mechanism of Folium Artemisiae argyi in treating atherosclerosis. It also suggests a reliable approach in investigating the therapeutic effect of traditional Chinese herbal medicine in treating Atherosclerotic cardiovascular disease (ASCVD).
从中药系统药理学数据库和分析平台筛选艾叶的有效成分及其相关靶基因。在 MalaCards 和 OMIM 数据库中搜索动脉粥样硬化的治疗靶点。京都基因与基因组百科全书（KEGG）通路分析在 WebGestalt 在线进行，并根据 ClueGo 和 Pedia 应用程序在 Cytoscape 中进行验证。然后，使用 STRING 数据库分析蛋白质-蛋白质相互作用网络，并使用 Cytoscape 构建。通过 GEO2R 在 GSE9128 和 GSE71226 中鉴定靶基因的差异表达。然后，使用分子操作环境进行分子对接。最后，通过 LPS 诱导的 Raw264.7 细胞，通过 qRT-PCR 和 Western blot 验证白细胞介素 6（IL-6）/IL-1β/MMP9 蛋白的表达。共鉴定出 232 个潜在靶基因和 8 种艾叶成分。槲皮素和柚皮素可能是治疗动脉粥样硬化的潜在候选生物活性物质。血管内皮生长因子（VEGFA）、MMP9 和 IL-1β 可能是潜在的靶基因。KEGG 分析表明，流体切应力和动脉粥样硬化途径在艾叶抗动脉粥样硬化作用中起着关键作用。基因表达综合数据库（GEO）验证表明，动脉粥样硬化患者的 VEGFA 下调，而 MMP9 和 IL-1β 上调。分子对接表明，只有 MMP9 与槲皮素结合良好。细胞实验结果表明，柚皮素和槲皮素有较强的抗炎作用，能显著抑制 MMP9 的表达。
实际应用
艾叶是一种传统的中草药，因其具有抗菌和抗炎作用而被广泛应用。本研究证明了艾叶治疗动脉粥样硬化的生物活性成分、潜在靶点和分子机制，为研究中药治疗动脉粥样硬化性心血管疾病（ASCVD）的疗效提供了一种可靠的方法。
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