Nantong University Medical School, Nantong, China.
Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Medicine (Baltimore). 2023 Jun 30;102(26):e34178. doi: 10.1097/MD.0000000000034178.
In recent years, with population aging and economic development, morbidity and mortality of atherosclerotic cardiovascular disease associated with atherosclerosis (AS) have gradually increased. In this study, a combination of network pharmacology and experimental verification was used to systematically explore the action mechanism of Yiqi Huoxue Huatan Recipe (YHHR) in the treatment of coronary atherosclerotic heart disease (CAD). We searched and screened the active ingredients of Coptis chinensis, Astragalus membranaceus, Salvia miltiorrhiza, and Hirudo. We also searched multiple databases for related target genes corresponding to the compounds and CAD. STRING was used to construct the protein-protein interaction (PPI) network of genes. Metascape was used to perform gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for common targets to analyze the main pathways, and finally, the molecular docking and main possible pathways were verified by experimental studies. Firstly, a total of 1480 predicted target points were obtained through the Swiss Target Prediction database. After screening, merging, and deleting duplicate values, a total of 768 targets were obtained. Secondly, "Coronary atherosclerotic heart disease" was searched in databases such as the OMIM, GeneCards, and TTD. 1844 disease-related targets were obtained. Among PPI network diagram of YHHR-CAD, SRC had the highest degree value, followed by AKT1, TP53, hsp90aa1 and mapk3. The KEGG pathway bubble diagram was drawn using Chiplot, the Signal pathways such as NF kappa B signaling pathway, Lipid and AS, and Apelin signaling pathway are closely related to the occurrence of CAD. The PCR and Western blot methods were used to detect the expression of NF-κB p65. When compared with that in the model group, the expression of NF-κB p65mRNA decreased in the low-concentration YHHR group, with P < .05, while the expression of NF-κB p65mRNA decreased significantly in the high-concentration YHHR group, with P < .01. On the other hand, when compared with that in the model group, the expression of NF-κB p65 decreased in the low-concentration YHHR group, but was not statistically significant, while the expression of NF-κB p65 was significant in the high-concentration YHHR group, and has statistical significance with P < .05. YHHR has been shown to resist inflammation and AS through the SRC/NF-κB signaling pathway.
近年来，随着人口老龄化和经济发展，与动脉粥样硬化（AS）相关的动脉粥样硬化性心血管疾病的发病率和死亡率逐渐升高。本研究采用网络药理学与实验验证相结合的方法，系统探讨益气活血化痰方（YHHR）治疗冠状动脉粥样硬化性心脏病（CAD）的作用机制。我们搜索和筛选了黄连、黄芪、丹参和水蛭的活性成分，并从多个数据库中搜索了与化合物和 CAD 相关的相关靶基因。使用 STRING 构建基因的蛋白质-蛋白质相互作用（PPI）网络。使用 Metascape 对共同靶标进行基因本体论（GO）富集分析和京都基因与基因组百科全书（KEGG）富集分析，分析主要通路，最后通过实验研究验证分子对接和主要可能通路。首先，通过 SwissTargetPrediction 数据库获得了 1480 个预测靶点。筛选、合并和删除重复值后，共获得 768 个靶点。其次，在 OMIM、GeneCards 和 TTD 等数据库中搜索“冠状动脉粥样硬化性心脏病”，共获得 1844 个疾病相关靶点。在 YHHR-CAD 的 PPI 网络图中，SRC 的度数值最高，其次是 AKT1、TP53、hsp90aa1 和 mapk3。使用 Chiplot 绘制 KEGG 通路气泡图，与 CAD 发生密切相关的信号通路如 NF-κB 信号通路、脂质和 AS、Apelin 信号通路等。采用 PCR 和 Western blot 方法检测 NF-κB p65 的表达。与模型组相比，低浓度 YHHR 组 NF-κB p65mRNA 表达降低，P＜0.05，而高浓度 YHHR 组 NF-κB p65mRNA 表达显著降低，P＜0.01。另一方面，与模型组相比，低浓度 YHHR 组 NF-κB p65 表达降低，但无统计学意义，而高浓度 YHHR 组 NF-κB p65 表达显著降低，P＜0.05。YHHR 通过 SRC/NF-κB 信号通路显示出抗炎和抗 AS 的作用。
