Chuanxiong-Chishao extract promotes mesenchymal stem cell-mediated angiogenesis in ischemic myocardial infarction

Ischemic heart disease remains a leading cause of mortality worldwide. Although mesenchymal stem cell (MSC) transplantation offers a promising strategy for myocardial infarction, its therapeutic efficacy is limited by poor cell survival and insufficient regenerative capacity. Traditional Chinese medicine has been widely used to promote blood circulation and treat ischemic diseases. Chuanxiong-Chishao (Ligusticum chuanxiong and Paeoniae Radix Rubra) is a commonly used herb pair for this purpose. This study aimed to investigate whether Chuanxiong-Chishao combined with MSCs could synergistically enhance angiogenesis after myocardial infarction. A rat model of myocardial infarction (MI) was established by permanent ligation of the left anterior descending coronary artery, and the animals were randomly assigned to the sham, model, MSCs, and Chuanxiong-Chishao combined with MSCs (CC-MSCs) groups. MSCs were injected intramyocardially immediately after ligation, and herbal treatment was administered for 28 days. Cardiac function was evaluated by echocardiography, myocardial fibrosis by Masson staining, and angiogenesis by CD31 immunofluorescence. Proteomic profiling was performed using label-free quantitative analysis, and key proteins were validated by Western blot. Compared with MSCs alone, CC-MSCs significantly improved left ventricular ejection fraction, fractional shortening, and cardiac output, reduced infarct size, and enhanced neovascularization in MI rats. Proteomic analysis identified 154 differentially expressed proteins between the model and CC-MSCs groups, and Gene Ontology enrichment analysis indicated significant activation of angiogenesis-related processes. Among these proteins, CDC42, NRP1, and AMOT were markedly altered, which was further confirmed by Western blot analysis. These findings suggest that Chuanxiong-Chishao enhances MSC-mediated angiogenesis and cardiac repair after MI, potentially through modulation of angiogenesis-related protein networks.