Exploring the Constituents and Mechanisms of Polygonum multiflorum Thunb. in Mitigating Ischemic Stroke: A Network Pharmacology and Molecular Docking Study

IF 1.6 4区医学 Q4 BIOCHEMICAL RESEARCH METHODS

Combinatorial chemistry & high throughput screening Pub Date : 2024-04-16 DOI:10.2174/0113862073285988240229081558

Lingyu Ruan, Mengyun Zheng, Xinru Xia, Chaofan Pang, Yating Wang, Zhiwei Fan, Jingtian Yang, Qing Qing, Hongyan Lin, Yuheng Tao, Junsong Wang, Liqun Wang

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引用次数: 0

Abstract

:: Polygonum multiflorum Thunb. (PMT) has shown promise in exerting cerebrovascular protective effects, and its potential for treating ischemic stroke (IS) has garnered attention. However, the lack of clarity regarding its chemical constituents and mechanisms has significantly hindered its clinical application. In this study, we employed network pharmacology and molecular docking techniques for the first time to elucidate the potential compounds and targets of PMT in treating IS. The databases CTD, DrugBank, DisGeNET, GeneCards, OMIM, TTD, PGKB, NCBI, TCMIP, CNKI, PubMed, ZINC, STITCH, BATMAN, ETCM and Swiss provided information on targets related to IS and components of PMT, along with their associated targets. We constructed “compound-target” and protein-protein interaction (PPI) networks sourced from the STRING database using the Cytoscape software. Gene Ontology (GO) enrichment analysis and KEGG pathway analysis were conducted using the DAVID database. Molecular docking between core targets and active compounds was conducted using Autodock4 software. Experiments were performed in an oxygen-glucose deprivation and reperfusion (OGD/R) model to validate the anti-IS activity of compounds isolated from PMT preliminarily. Network pharmacological analysis revealed 16 core compounds, including resveratrol, polydatin, TSG, ω- hydroxyemodin, emodin anthrone, tricin, moupinamide, and others, along with 11 high-degree targets, such as PTGS1, PTGS2, ADORA1, ADORA2, CA1, EGFR, ESR1, ESR2, SRC, MMP3 and MMP9. GO and KEGG enrichment analyses revealed the involvement of HIF-1, Akt signaling pathway and energy metabolism-related signaling pathways. Molecular docking results emphasized eight key compounds and confirmed their interactions with corresponding targets. In vitro OGD/R model experiments identified TSG and tricin as the primary active substances within PMT for its anti-stroke activity. This study contributes new insights into the potential development of PMT for stroke prevention and treatment.

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探索何首乌缓解缺血性中风的成分和机制：网络药理学和分子对接研究

::何首乌（Polygonum multiflorum Thunb.，PMT）具有保护脑血管的作用，其治疗缺血性中风（IS）的潜力已引起人们的关注。然而，由于其化学成分和机理尚不明确，大大阻碍了其临床应用。在本研究中，我们首次采用了网络药理学和分子对接技术来阐明 PMT 治疗 IS 的潜在化合物和靶点。CTD、DrugBank、DisGeNET、GeneCards、OMIM、TTD、PGKB、NCBI、TCMIP、CNKI、PubMed、ZINC、STITCH、BATMAN、ETCM和Swiss等数据库提供了与IS和PMT成分有关的靶点及其相关靶点的信息。我们使用 Cytoscape 软件从 STRING 数据库中构建了 "化合物-靶标 "和蛋白质-蛋白质相互作用（PPI）网络。我们使用 DAVID 数据库进行了基因本体（GO）富集分析和 KEGG 通路分析。使用 Autodock4 软件在核心靶标和活性化合物之间进行分子对接。在氧-葡萄糖剥夺和再灌注（OGD/R）模型中进行了实验，以初步验证从 PMT 中分离出的化合物的抗 IS 活性。网络药理学分析发现了16种核心化合物，包括白藜芦醇、多靛红、TSG、ω-羟基大黄素、大黄素蒽酮、三嗪、毛蕊花酰胺等，以及11个高度靶点，如PTGS1、PTGS2、ADORA1、ADORA2、CA1、表皮生长因子受体、ESR1、ESR2、SRC、MMP3和MMP9。GO 和 KEGG 富集分析表明，HIF-1、Akt 信号通路和能量代谢相关信号通路参与了研究。分子对接结果强调了八个关键化合物，并证实了它们与相应靶点的相互作用。体外 OGD/R 模型实验确定 TSG 和三尖杉苷是 PMT 抗中风活性的主要活性物质。这项研究为开发 PMT 预防和治疗中风的潜力提供了新的见解。

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来源期刊

Combinatorial chemistry & high throughput screening 化学-生化研究方法

CiteScore

3.10

自引率

5.60%

发文量

327

审稿时长

7.5 months

期刊介绍： Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal: Target identification and validation Assay design, development, miniaturization and comparison High throughput/high content/in silico screening and associated technologies Label-free detection technologies and applications Stem cell technologies Biomarkers ADMET/PK/PD methodologies and screening Probe discovery and development, hit to lead optimization Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) Chemical library design and chemical diversity Chemo/bio-informatics, data mining Compound management Pharmacognosy Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products) Natural Product Analytical Studies Bipharmaceutical studies of Natural products Drug repurposing Data management and statistical analysis Laboratory automation, robotics, microfluidics, signal detection technologies Current & Future Institutional Research Profile Technology transfer, legal and licensing issues Patents.