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基于网络药理学的白藜芦醇治疗子痫前期作用机制研究——调控 AGE-RAGE 和 HIF-1 信号通路

A network pharmacology study on mechanism of resveratrol in treating preeclampsia regulation of AGE-RAGE and HIF-1 signalling pathways.

机构信息

Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, China.

出版信息

Front Endocrinol (Lausanne). 2023 Jan 5;13:1044775. doi: 10.3389/fendo.2022.1044775. eCollection 2022.

Abstract

BACKGROUND

Preeclampsia (PE) is a hypertensive disorder of pregnancy that threatens the lives of millions of pregnant women and their babies worldwide. Without effective medications, there are thousands of maternal and child mortalities every year. Resveratrol (RSV), a non-flavonoid polyphenol extracted from multiple plants, has shown positive effects in treating hypertension, cardiovascular disorders, and even PE. This study aimed to explore the pharmacological mechanism of RSV in treating PE by using network pharmacology and bioinformatics.

METHODS

With the use of multiple databases, 66 intersecting targets were obtained from the 347 putative targets of RSV and 526 PE-related genes. Then, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted to investigate the functions of the intersecting targets. The protein-protein interaction network and target-pathway network were drawn and analyzed to illustrate the correlation between targets and pathways. Finally, molecular docking was conducted to calculate the binding energy between RSV and core targets.

RESULTS

The results showed that the core targets of RSV were IL6, TNF, IL1B, VEGFA, STAT3, and EGFR. There existed good binding between RSV and IL6, TNF, IL1B, VEGFA, and EGFR. In addition, we found that RSV mainly functioned in the AGE-RAGE and HIF-1 signaling pathways, which are associated with the occurrence and development of PE.

CONCLUSION

In conclusion, our findings indicated that RSV has the effects of regulating angiogenesis and anti-inflammation and can be a candidate medicine for treating PE.

摘要

背景

子痫前期(PE)是一种妊娠高血压疾病,威胁着全球数百万孕妇及其婴儿的生命。由于缺乏有效的药物,每年都有数千例母婴死亡。白藜芦醇(RSV)是一种从多种植物中提取的非黄酮多酚,已显示出在治疗高血压、心血管疾病甚至 PE 方面的积极作用。本研究旨在利用网络药理学和生物信息学方法探讨 RSV 治疗 PE 的药理机制。

方法

利用多个数据库,从 RSV 的 347 个假定靶点和 526 个 PE 相关基因中获得了 66 个交集靶点。然后,进行基因本体(GO)分析和京都基因与基因组百科全书(KEGG)分析,以研究交集靶点的功能。绘制并分析蛋白质-蛋白质相互作用网络和靶标-通路网络,以说明靶标与通路之间的相关性。最后,进行分子对接计算 RSV 与核心靶标的结合能。

结果

结果表明,RSV 的核心靶标为 IL6、TNF、IL1B、VEGFA、STAT3 和 EGFR。RSV 与 IL6、TNF、IL1B、VEGFA 和 EGFR 之间存在良好的结合。此外,我们发现 RSV 主要作用于 AGE-RAGE 和 HIF-1 信号通路,这些通路与 PE 的发生和发展有关。

结论

总之,我们的研究结果表明,RSV 具有调节血管生成和抗炎的作用,可能成为治疗 PE 的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a64/9849370/940a4347717c/fendo-13-1044775-g001.jpg

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