Predicting the Pharmacological Targets of Astragalus membranaceus against Hypertensive Nephropathy

IF 1.2 4区医学 Q4 CHEMISTRY, MEDICINAL

Letters in Drug Design & Discovery Pub Date : 2024-03-01 DOI:10.2174/0115701808285471240216040105

Ningxin Zhang, Chen Guan, Lingyu Xu, Zengying Liu, Chenyu Li, Quandong Bu, Xuefei Shen, Yan Xu

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引用次数: 0

Abstract

Objective: Hypertension is one of the main causes of chronic kidney disease. Astragalus membranaceus (AM), an important traditional Chinese medicine for treating hypertensive nephropathy, has a complex composition that makes it challenging to explore its mechanism of action and limits its clinical application. This study aims to investigate the underlying mechanism of AM in treating hypertensive nephropathy. Methods: We retrieved all the compound data of AM from the Traditional Chinese Medicine Systems Pharmacology database and screened out the active compounds and their target proteins. Then, a network of candidate compounds and target compounds of AM was constructed using Cytoscape software. Furthermore, hypertensive nephropathy-related genes from the DisGeNET and GeneCards databases were intersected with AM target proteins and hypertensive nephropathy-related genes to determine the potential targets of AM in treating hypertensive nephropathy. Finally, after performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, we conducted molecular docking to verify the interaction between the main active ingredients of AM and the core targets. Results: A total of 87 effective components of AM were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. According to the network of active compounds and their target proteins, 18 of the 20 effective compounds in AM could act on 210 proteins. Taking the intersection of 274 hypertensive nephropathy-related genes and AM target proteins, 49 potential targets of AM in treating hypertensive nephropathy were identified. Using the median degree value, we determined 25 core targets of AM in treating hypertensive nephropathy. GO enrichment analysis showed that the biological processes of AM on hypertensive nephropathy mainly focused on the inflammatory response, hypoxia response, angiogenesis, cell proliferation, and cell migration. KEGG pathway enrichment analysis mainly involved cancer pathways, the AGE-RAGE signaling pathway in diabetic complications, blood flow shear stress, and atherosclerosis. Molecular docking results showed that quercetin, kaempferol, and 7-O-methylisomucronulatol had strong binding activity with several target proteins and may exert protective effects by stabilizing the interaction between molecules through the intermolecular forces of hydrogen bonds. Conclusion: This study reveals the targets of AM in treating hypertensive nephropathy using network pharmacology and molecular docking, providing new clues for developing novel drugs for hypertensive nephropathy and basic research development.

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预测黄芪防治高血压肾病的药理靶点

目的：高血压是导致慢性肾病的主要原因之一。黄芪（AM）是治疗高血压肾病的重要中药，但其成分复杂，对其作用机制的探索具有挑战性，限制了其临床应用。本研究旨在探讨黄芪治疗高血压肾病的内在机制。研究方法从中药系统药理学数据库中检索AM的所有化合物数据，筛选出活性化合物及其靶蛋白。然后，使用 Cytoscape 软件构建 AM 候选化合物和靶标化合物网络。此外，还将 DisGeNET 和 GeneCards 数据库中的高血压肾病相关基因与 AM 靶蛋白和高血压肾病相关基因进行交叉，以确定 AM 治疗高血压肾病的潜在靶点。最后，在进行基因本体（GO）和京都基因组百科全书（KEGG）通路富集分析后，我们进行了分子对接，以验证AM的主要活性成分与核心靶点之间的相互作用。结果发现我们从中药系统药理学（TCMSP）数据库中获得了87种AM的有效成分。根据有效成分及其靶蛋白网络，AM 的 20 种有效成分中有 18 种可作用于 210 种蛋白。根据 274 个高血压肾病相关基因和 AM 靶蛋白的交叉点，确定了 49 个 AM 治疗高血压肾病的潜在靶点。根据中位度值，我们确定了25个AM治疗高血压肾病的核心靶点。GO富集分析表明，AM对高血压肾病的生物学过程主要集中在炎症反应、缺氧反应、血管生成、细胞增殖和细胞迁移等方面。KEGG 通路富集分析主要涉及癌症通路、糖尿病并发症中的 AGE-RAGE 信号通路、血流剪切应力和动脉粥样硬化。分子对接结果表明，槲皮素、山柰醇和 7-O-甲基异桉叶油醇与多个靶蛋白有很强的结合活性，可能通过分子间的氢键作用力稳定分子间的相互作用，从而发挥保护作用。结论本研究利用网络药理学和分子对接揭示了AM治疗高血压肾病的靶点，为开发治疗高血压肾病的新药和基础研究提供了新的线索。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Letters in Drug Design & Discovery 医学-医药化学

CiteScore

1.80

自引率

10.00%

发文量

245

审稿时长

3 months

期刊介绍： Aims & Scope Letters in Drug Design & Discovery publishes letters, mini-reviews, highlights and guest edited thematic issues in all areas of rational drug design and discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. The emphasis is on publishing quality papers very rapidly by taking full advantage of latest Internet technology for both submission and review of manuscripts. The online journal is an essential reading to all pharmaceutical scientists involved in research in drug design and discovery.