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基于网络药理学和体外实验证明补阳还五汤有效抑制心肌纤维化。

Based on network pharmacology and in vitro experiments to prove the effective inhibition of myocardial fibrosis by Buyang Huanwu decoction.

机构信息

The 2nd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.

The 1st Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.

出版信息

Bioengineered. 2022 May;13(5):13767-13783. doi: 10.1080/21655979.2022.2084253.

Abstract

Among cardiovascular diseases, myocardial fibrosis (MF) is a major pathological change underlying heart failure and is associated with a high mortality rate. However, the molecular mechanism underlying MF has remained elusive. Buyang Huanwu decoction (BYHWD), a traditional Chinese medicine (TCM) formula for cardiovascular diseases, exhibits good anti-inflammatory and blood-activating properties. In the present study, we studied the MF inhibitory effect of BYHWD using network pharmacology and experimental validation. We used several databases to collect information on MF and related drugs and finally obtained cross-targets for BYHWD and MF. After that we got protein-protein interaction (PPI) network and performed gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses to obtain key signaling pathways for further study. After screening, interleukin (IL)-6, IL-1β, and matrix metallopeptidase 9 (MMP9) were selected for experiments, which included cell cycle studies, cell migration rate, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and western blotting (WB). Finally, molecular docking was performed to validate the results. We found 299 common targets between BYHWD and MF. In total, 75 core targets of the PPI core network were selected for enrichment analysis, and the IL-17 signaling pathway, which is intricately linked to inflammation, was speculated to be involved. Accordingly, experiments were performed. Altogether, our findings indicated that BYHWD can affect the function of cardiac fibroblasts and reduce the expression of inflammatory factors in rats. In summary, BYHWD can inhibit MF by reducing the expression of inflammatory factors and affecting the IL-17 signaling pathway.

摘要

在心血管疾病中,心肌纤维化 (MF) 是心力衰竭的主要病理变化,与高死亡率相关。然而,MF 的分子机制仍然难以捉摸。补阳还五汤 (BYHWD) 是一种治疗心血管疾病的中药方剂,具有良好的抗炎和活血作用。本研究采用网络药理学和实验验证方法研究 BYHWD 对 MF 的抑制作用。我们使用多个数据库收集 MF 和相关药物的信息,最终获得 BYHWD 和 MF 的交叉靶点。然后我们得到蛋白质-蛋白质相互作用 (PPI) 网络,并进行基因本体论 (GO) 和京都基因与基因组百科全书 (KEGG) 通路富集分析,以获得进一步研究的关键信号通路。筛选后,选择白细胞介素 (IL)-6、IL-1β 和基质金属蛋白酶 9 (MMP9) 进行实验,包括细胞周期研究、细胞迁移率、定量逆转录聚合酶链反应 (qRT-PCR) 和蛋白质印迹 (WB)。最后,进行分子对接验证结果。我们发现 BYHWD 和 MF 之间有 299 个共同靶点。总共选择了 PPI 核心网络的 75 个核心靶标进行富集分析,推测与炎症密切相关的 IL-17 信号通路可能参与其中。因此,进行了实验。总之,我们的研究结果表明,BYHWD 可以通过影响心肌成纤维细胞的功能和降低大鼠炎症因子的表达来抑制 MF。综上所述,BYHWD 可以通过降低炎症因子的表达和影响 IL-17 信号通路来抑制 MF。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/064f/9275964/948a23b9e70d/KBIE_A_2084253_UF0001_OC.jpg

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