Exploring the Myocardial Protective Mechanism of Total Flavonoids of Apocynum venetum L. Based on Network Pharmacology and Animal Experiments

UPLC-MS/MS chemical composition identification showed that a total of 72 flavonoid compounds were identified. three major active components(luteolin, catechin,and kaempferol) and 75 common targets were screened out by network pharmacology methods, among which eight proteins including protein kinase B1 (AKT1), prostaglandin-endoperoxide synthase 2 (PTGS2), SRC, B-cell lymphoma/leukemia 2 (BCL2), and matrix metallopeptidase 9 (MMP9) were identified as core targets; GO analysis indicated that the main targets are involved in apoptotic processes; while KEGG analysis showed significant enrichment of the phosphatidylinositol 3 kinase-protein kinase B (PI3K-AKT) signaling pathway (P < 0.05).

Molecular docking demonstrated that the three active components all stably bound to PTGS2, SRC, BCL2, and MMP9 proteins (binding energies < −7 kcal/mol). Animal experiments showed that AVL total flavonoids significantly reduced myocardial infarct size (P < 0.05), ameliorated histopathological damage, and decreased the apoptotic rate (P < 0.05); downregulated the protein expression of PTGS2 and MMP9 (P < 0.05), while upregulated BCL2 and SRC protein expression (P < 0.05); and LY294002 reversed the effects of AVL total flavonoids on p-AKT and SRC.

In conclusion, AVL total flavonoids may protect the myocardium by binding to SRC and thereby regulating the PI3K-AKT signaling pathway.