ABSTRACT
Objective: To study the mechanism of Salviae Miltiorrhizae Radix (SMR) et Rhizoma and Carthamii Flos (CF) in the treatment of myocardial infarction (MI) by means of network pharmacology and experimental verification. Methods: The main components of SMR-CF were searched by Traditional Chinese Medicine System Pharmacological Analysis Platform (TCMSP), and the component targets were screened by TCMSP and Swiss Target prediction databases, and the MI related targets were queried through OMIM, TTD, Genecards and NCBI (Gene) databases. The common target proteins of disease and drug components were screened by the intersection of drug targets and disease targets. The network model of protein-protein interaction (PPI) was constructed by using STRING platform. The functional enrichment analysis of gene ontology (GO) and the KEGG pathway were carried out by using DAVID. Cytoscape was used to construct medicinal material-target and medicinal material-composition-target-pathway network map for further experimental verification, in order to reveal the therapeutic effect of SMR-CF on MI in mice. Results: A total of 84 active components were screened from SMR and CF, 485 target proteins were searched, and 28 targets related to MI were found. GO functional enrichment analysis showed that there were 18 GO entries, including 9 biological process (BP) entries, three molecular functional (MF) entries and six cell composition (CC) entries. KEGG pathway was enriched and screened to obtain 30 signal pathways, such as hypoxia inducible factor signaling pathway, tumor necrosis factor, vascular endothelial growth factor, sheath phospholipid, small G protein Rap1 and so on. The results of HE staining and Masson staining showed that SMR-CF could significantly improve myocardial injury. Western blotting results showed that SMR-CF could down-regulate the expression of TNF-α and MAPK to improve myocardial injury. Conclusion: The target and pathway of SMR-CF in the treatment of MI are explained by network pharmacology, which provides a scientific basis for the further clarification of SMR-CF in the treatment of MI.
ABSTRACT
Objective: To investigate the protective effect of compound Longmaining isoprenaline hydrochloride-induced myocardial infarction model and its effect on Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear transcription factor-kappa B (NF-κB) signaling pathway.Method: Forty-eight male SD rats were randomly divided into 6 groups:normal group,model group,compound salvia miltiorrhiza drop pill group (0.072 9 g·kg-1),and low,medium and high-dose compound Longmaining decoction groups (0.36,0.71,1.43 g·kg-1).The acute myocardial infarction model was induced through subcutaneous injection with isoproterenol.The pathological changes of myocardial tissue were examined by hematoxylin-eosin (HE) staining.The levels of interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),monocyte chemotaxis protein-1(MCP-1) and nitrogen (NO) in serum were measured by enzyme linked immunosorbent assay (ELISA).The expression levels of inhibitors of NF-κB kinase subunit-β(IKKβ),NF-κB inhibitor α(IκBα),TLR4,MyD88 and NF-κB p65 were measured by immunohistochemical staining and Western blot.Result: Compared with normal group,the myocardial injury in model group was obvious.The levels of IL-1β,IL-6,TNF-α,MCP-1 and NO in serum increased significantly (PκBα decreased significantly (Pβ,TLR4,MyD88 and NF-κB p65 increased significantly in myocardial tissue (Pβ,IL-6,TNF-α,MCP-1 and NO levels in the serum (PκBα(Pβ,TLR4,MyD88 and NF-κB p65(PConclusion: Compound Longmaining plays a protective effect on acute myocardial infarction by regulatingthe expressions of TLR4/MyD88/NF-κB p65 signaling pathway and relevant inflammatory factors.