Exploring the Cardioprotective Mechanisms of Ligusticum wallichii in Myocardial Infarction Through Network Pharmacology and Experimental Validation.

IF 5.1 2区医学 Q1 CHEMISTRY, MEDICINAL Drug Design, Development and Therapy Pub Date : 2025-01-17 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S481499

Huan Yang, Jun Cao, Lijie Zhou, Jiangchuan Chen, Jiaman Tang, Jiamei Chen, Lengyun Yin, Li Xie, Jianmin Li, Jinwen Luo

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Abstract

Background: Myocardial infarction represents a coronary artery ailment with the highest incidence and fatality rates among cardiovascular conditions. However, effective pharmacological interventions remain elusive. This study seeks to elucidate the molecular mechanisms underlying the effects of Ligusticum wallichii on myocardial infarction through network pharmacology and experimental validation.

Methods: Initially, potential targets of Ligusticum wallichii's active ingredients and myocardial infarction-related targets were retrieved from databases. Subsequently, core targets of Ligusticum wallichii on myocardial infarction were identified via the PPI network analysis and subjected to GO and KEGG pathway enrichment analyses. Molecular docking was employed to validate the binding affinities between the core targets and the bioactive components. The findings from network pharmacology analysis were corroborated through in vitro and in vivo experiments.

Results: Seven active ingredients from Ligusticum wallichii were identified, corresponding to 122 targets. Molecular docking revealed robust binding affinities of Myricanone, Senkyunone, and Sitosterol to key target proteins (EGFR, STAT3, and SRC). In vitro, experiments demonstrated that pretreatment with the active components of Ligusticum wallichii protected myocardial cells from OGD exposure and modulated the expression of their key target genes. In vivo, experiments showed that the active components of Ligusticum wallichii significantly improved myocardial infarction via alleviating myocardial fibrosis and oxidative stress and did not elicit toxic effects in mice.

Conclusion: The collective findings suggest that Ligusticum wallichii shows promising potential for myocardial infarction treatment by regulating key target proteins (EGFR, STAT3, and SRC), which play roles in oxidative stress and myocardial fibrosis.

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通过网络药理学和实验验证探讨川芎对心肌梗死的保护作用机制。

背景：心肌梗死是心血管疾病中发病率和死亡率最高的冠状动脉疾病。然而，有效的药物干预仍然难以捉摸。本研究旨在通过网络药理学和实验验证来阐明川芎抗心肌梗死的分子机制。方法：首先从数据库中检索川芎有效成分的潜在靶点和心肌梗死相关靶点。随后，通过PPI网络分析确定川芎对心肌梗死的核心靶点，并进行GO和KEGG通路富集分析。通过分子对接验证核心靶点与生物活性成分之间的结合亲和力。网络药理学分析的结果通过体外和体内实验得到证实。结果：从川芎中鉴定出7种有效成分，对应靶点122个。分子对接发现，Myricanone、Senkyunone和谷甾醇与关键靶蛋白（EGFR、STAT3和SRC）具有很强的结合亲和力。体外实验表明，川芎有效成分预处理对OGD暴露心肌细胞具有保护作用，并可调节其关键靶基因的表达。体内实验表明，川芎有效成分通过减轻心肌纤维化和氧化应激，显著改善心肌梗死，且对小鼠无毒性作用。结论：综合研究结果表明，川芎通过调节在氧化应激和心肌纤维化中起作用的关键靶蛋白（EGFR、STAT3和SRC），具有治疗心肌梗死的良好潜力。

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

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.