The Molecular Mechanism of Radix Paeoniae Rubra.-Cortex Moutan. Herb Pair in the Treatment of Atherosclerosis: A Work Based on Network Pharmacology and In Vitro Experiments.

IF 3.4 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Cardiovascular Toxicology Pub Date : 2024-08-01 Epub Date: 2024-07-01 DOI:10.1007/s12012-024-09881-2
Caojian Zuo, Lidong Cai, Ya Li, Chencheng Ding, Guiying Liu, Changmei Zhang, Hexiang Wang, Yang Zhang, Mingyue Ji
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Abstract

Radix Paeoniae Rubra. (Chishao, RPR) and Cortex Moutan. (Mudanpi, CM) are a pair of traditional Chinese medicines that play an important role in the treatment of atherosclerosis (AS). The main objective of this study was to identify potential synergetic function and underlying mechanisms of RPR-CM in the treatment of AS. The main active ingredients, targets of RPR-CM and AS-related genes were obtained from public databases. A Venn diagram was utilized to screen the common targets of RPR-CM in treating AS. The protein-protein interaction network was established based on STRING database. Biological functions and pathways of potential targets were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Cytoscape was used to construct the drug-compound-target-signal pathway network. Molecular docking was performed to verify the binding ability of the bioactive ingredients and the target proteins. The endothelial inflammation model was constructed with human umbilical vein endothelial cells stimulated with ox-LDL, and the function of RPR-CM in treating AS was verified by CCK-8 assay, enzyme-linked immunosorbent assay, and qPCR. In this study, 12 active components and 401 potential target genes of RPR-CM were identified, among which quercetin, kaempferol and baicalein were considered to be the main active components. A total of 1903 AS-related genes were identified through public databases and four GEO datasets (GSE57691, GSE72633, GSE6088 and GSE199819). There are 113 common target genes of RPR-CM in treating AS. PPI network analysis identified 17 genes in cluster 1 as the core targets. Bioinformatics analysis showed that RPR-CM in AS treatment was associated with multiple downstream biological processes and signal pathways. PTGS2, JUN, CASP3, TNF, IL1B, IL6, FOS, STAT1 were identified as the core targets of RPR-CM, and molecular docking showed that the main bioactive components of RPR-CM had good binding ability with the core targets. RPR-CM extract significantly inhibited the levels of inflammatory factors TNF-α, IL-6, IL-1β, MCP-1, VCAM-1 and ICAM-1 in HUVECs, and inhibited endothelial inflammation. This study revealed the active ingredients of RPR-CM, and identified the key downstream targets and signaling pathways in the treatment of AS, providing theoretical basis for the application of RPR-CM in prevention and treatment of AS.

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芍药牡丹合剂治疗动脉粥样硬化的分子机制研究治疗动脉粥样硬化的草药对:基于网络药理学和体外实验的研究。
赤芍(赤芍)和牡丹皮(Cortex Moutan.(牡丹皮)是一对传统中药,在治疗动脉粥样硬化(AS)方面发挥着重要作用。本研究的主要目的是确定 RPR-CM 在治疗 AS 方面的潜在协同功能和内在机制。研究人员从公共数据库中获取了 RPR-CM 的主要活性成分、靶点和 AS 相关基因。利用维恩图筛选 RPR-CM 治疗强直性脊柱炎的共同靶点。基于 STRING 数据库建立了蛋白质-蛋白质相互作用网络。通过基因本体论(Gene Ontology)和京都基因组百科全书(Kyoto Encyclopedia of Genes and Genomes)的富集分析,分析了潜在靶点的生物学功能和通路。使用 Cytoscape 构建了药物-化合物-靶点-信号通路网络。通过分子对接验证了生物活性成分与靶蛋白的结合能力。用人脐静脉内皮细胞在 ox-LDL 刺激下构建了内皮炎症模型,并通过 CCK-8 检测法、酶联免疫吸附法和 qPCR 验证了 RPR-CM 治疗强直性脊柱炎的功能。本研究鉴定了 RPR-CM 的 12 种活性成分和 401 个潜在靶基因,其中槲皮素、山柰酚和黄芩苷被认为是主要的活性成分。通过公共数据库和四个 GEO 数据集(GSE57691、GSE72633、GSE6088 和 GSE199819)共鉴定出 1903 个 AS 相关基因。RPR-CM在治疗强直性脊柱炎方面有113个共同的靶基因。PPI网络分析发现第1群组中有17个基因是核心靶点。生物信息学分析表明,RPR-CM在强直性脊柱炎治疗中与多个下游生物过程和信号通路相关。PTGS2、JUN、CASP3、TNF、IL1B、IL6、FOS、STAT1被确定为RPR-CM的核心靶点,分子对接显示RPR-CM的主要生物活性成分与核心靶点具有良好的结合能力。RPR-CM提取物能明显抑制HUVECs中炎症因子TNF-α、IL-6、IL-1β、MCP-1、VCAM-1和ICAM-1的水平,抑制内皮炎症。该研究揭示了RPR-CM的活性成分,确定了其治疗强直性脊柱炎的关键下游靶点和信号通路,为RPR-CM在强直性脊柱炎预防和治疗中的应用提供了理论依据。
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来源期刊
Cardiovascular Toxicology
Cardiovascular Toxicology 医学-毒理学
CiteScore
6.60
自引率
3.10%
发文量
61
审稿时长
>12 weeks
期刊介绍: Cardiovascular Toxicology is the only journal dedicated to publishing contemporary issues, timely reviews, and experimental and clinical data on toxicological aspects of cardiovascular disease. CT publishes papers that will elucidate the effects, molecular mechanisms, and signaling pathways of environmental toxicants on the cardiovascular system. Also covered are the detrimental effects of new cardiovascular drugs, and cardiovascular effects of non-cardiovascular drugs, anti-cancer chemotherapy, and gene therapy. In addition, Cardiovascular Toxicology reports safety and toxicological data on new cardiovascular and non-cardiovascular drugs.
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