Exploring the Cardioprotective Mechanisms of Ligusticum wallichii in Myocardial Infarction Through Network
Huan Yang1, Jun Cao1, Lijie Zhou1
1Department of Pulmonary and Critical Care Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Clinical Medicine Research Center For Respiratory Rehabilitation in Hunan Province, Changsha, Hunan, People's Republic of China.
Insights
Ligusticum wallichii demonstrates potential for treating myocardial infarction by targeting key proteins involved in oxidative stress and fibrosis. This study validated its protective effects on heart cells and in mice.
Area of Science:
- Cardiovascular Pharmacology
- Traditional Chinese Medicine
- Systems Biology
Background:
- Myocardial infarction (MI) is a leading cause of death with limited pharmacological treatments.
- Understanding the molecular basis of MI is crucial for developing effective therapies.
- Ligusticum wallichii is explored for its potential therapeutic effects on MI.
Purpose of the Study:
- To investigate the molecular mechanisms of Ligusticum wallichii in treating myocardial infarction.
- To identify key targets and pathways affected by Ligusticum wallichii using network pharmacology.
- To validate the findings through experimental studies.
Main Methods:
- Network pharmacology approach to identify active compounds and targets of Ligusticum wallichii.
- Protein-protein interaction (PPI) network analysis to determine core targets.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.
- Molecular docking to assess binding affinity of active compounds to core targets.
- In vitro and in vivo experimental validation.
Main Results:
- Seven active ingredients and 122 targets of Ligusticum wallichii were identified.
- Myricanone, Senkyunone, and Sitosterol showed strong binding to key targets (EGFR, STAT3, SRC).
- In vitro studies confirmed protection of myocardial cells against oxygen-glucose deprivation (OGD).
- In vivo studies demonstrated improved MI outcomes, reduced fibrosis and oxidative stress, with no observed toxicity.
Conclusions:
- Ligusticum wallichii exhibits promising therapeutic potential for myocardial infarction.
- The herb acts by regulating key target proteins like EGFR, STAT3, and SRC.
- These targets are implicated in crucial pathological processes of MI, including oxidative stress and myocardial fibrosis.
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.
