Role of jianxin granules in heart failure: evidence from network pharmacology, molecular docking and experimental verification.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-03-29 DOI:10.23736/S2724-5683.24.06511-6

Qiufang Ouyang, Luting Zhang, Yongzhong Chen, Leilei Liu, Meihua Chen, Jinxian Yan, Tao You, Jinjian Guo

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引用次数: 0

Abstract

Background: Jianxin (JX) granules is a traditional Chinese medicine widely used in the treatment of heart failure (HF), but the mechanism is unclear. This study aimed to investigate the mechanism of JX granules in the treatment of HF based on network pharmacology analysis and in-vivo experiments.

Methods: A series of network pharmacology methods was employed to ascertain potential targets and critical pathways implicated in the therapeutic action of JX granules against HF. Subsequently, molecular docking was utilized to investigate the binding affinity of key active constituents within JX granules to these targets. In-vivo experiments, echocardiography, hematoxylin and eosin, Masson's trichrome assay, and western blot analysis were conducted to validate the efficacy and mechanism of JX granules in treating rats with HF.

Results: A total of 122 active components, 896 drug targets, 1216 HF-related targets, and 136 targets pertinent to drug-disease interactions were identified. 151 key targets and 725 core clusters were detected through protein-protein interaction network analysis. Among these, interleukin 6 (IL-6), vascular endothelial growth factor a (VEGFA), and serine/threonine kinase 1 (AKT1) were core hub genes. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis revealed the critical pathways, including epidermal growth factor receptor (EGFR), advanced glycation end products (AGEs) and their receptors (RAGE) pathway, along with hypoxia-inducible factor 1 (HIF-1) signaling pathway. Molecular docking studies demonstrated high binding affinities between key targets and the pivotal active ingredients of Danshenol A, salvianolic acid B, and arachidonic acid. Furthermore, animal studies corroborated that JX granules improve cardiac function and reduce myocardial fibrosis, potentially by modulating the expression of IL-6, VEGFA, and p-AKT1.

Conclusions: The bioactive components within JX granules, such as Danshenol A, salvianolic acid B, and arachidonic acid may exert therapeutic effects on HF through modulation of IL-6, VEGFA, and AKT1 gene expression. This study provides a scientific basis for subsequent clinical application of JX granules and an in-depth investigation of their mechanisms of action.

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健心颗粒在心力衰竭中的作用：来自网络药理学、分子对接和实验验证的证据。

背景：健心颗粒是一种广泛用于治疗心力衰竭（HF）的中药，但其作用机制尚不清楚。本研究旨在通过网络药理学分析和体内实验研究健心颗粒治疗心力衰竭的机制：方法：采用一系列网络药理学方法确定 JX 颗粒剂治疗高血压的潜在靶点和关键通路。随后，利用分子对接研究了 JX 颗粒中的关键活性成分与这些靶点的结合亲和力。通过体内实验、超声心动图、苏木精和伊红、Masson 三色试验和 Western 印迹分析，验证了 JX 颗粒治疗高血脂大鼠的疗效和机制：结果：共鉴定出 122 种活性成分、896 个药物靶点、1216 个高频相关靶点和 136 个与药物-疾病相互作用相关的靶点。通过蛋白质-蛋白质相互作用网络分析，发现了 151 个关键靶点和 725 个核心集群。其中，白细胞介素6（IL-6）、血管内皮生长因子a（VEGFA）和丝氨酸/苏氨酸激酶1（AKT1）是核心枢纽基因。京都基因和基因组百科全书（KEGG）富集分析揭示了关键通路，包括表皮生长因子受体（EGFR）、高级糖化终产物（AGEs）及其受体（RAGE）通路以及缺氧诱导因子 1（HIF-1）信号通路。分子对接研究表明，丹参酚 A、丹参酚酸 B 和花生四烯酸等关键活性成分与关键靶点之间具有很高的结合亲和力。此外，动物实验证实，JX 颗粒可通过调节 IL-6、VEGFA 和 p-AKT1 的表达，改善心脏功能并减轻心肌纤维化：结论：JX 颗粒中的生物活性成分，如丹参酚 A、丹参酚酸 B 和花生四烯酸，可能通过调节 IL-6、VEGFA 和 AKT1 基因的表达对高血压产生治疗作用。这项研究为 JX 颗粒后续的临床应用及其作用机制的深入研究提供了科学依据。

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

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.