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

IF 4.7 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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引用次数: 0

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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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.