Figure 1 Compound-targets network The pink square nodes displayed the herb name. The circle nodes displayed the active components of each herb. The red octagonal nodes displayed the common ingredients shared by various herbs. The blue diamond nodes displayed the related targets of DLT. Their degree value analyzed by Cytoscape were represented by the node size and transparency, whose larger size and darker color indicated a higher degree value. The interaction between the compounds and the related targets was performed by the edge. DLT: Danlou tablet.

Figure 2 Process of filtering core targets and the component-target-pathway network of DLT against myocardial I/R injury A, B: process of filtering core targets of DLT against myocardial I/R injury. A: 133 intersection targets uploaded into the STRING database, followed by 129 nodes representing the potential targets and 2060 edges representing their PPI network. Their degree value analyzed by Cytoscape were represented by the node size and color depth, whose larger size and darker depth indicated a higher degree value. The interactivity between the nodes was emerged by the edge. Their combined score analyzed by Cytoscape were represented by the color depth of edge, whose darker depth indicated a higher combined score. B: after that, we applied CytoNCA plug-in to conduct the network analysis of DC. There were 28 nodes representing the core targets and 510 protein interaction. Their degree value analyzed by Cytoscape were represented by the node size, whose larger size indicated a higher degree value. The interactivity between the nodes was emerged by the edge. Their combined score analyzed by Cytoscape were represented by the color depth of edge, whose darker depth indicated a higher combined score. C: the component-target-pathway network of DLT against myocardial I/R injury. Active chemical compounds in DLT, 28 core targets, and top 10 pathways constructed the network. Among them, the circle nodes displayed active chemical compounds in DLT. The diamond nodes displayed 28 core targets of DLT against I/R. The square nodes displayed the top 10 pathways. The degree value of nodes analyzed by Cytoscape were represented by the node size and color depth, whose larger size and darker color indicated a higher degree value. The interactivity between the compounds, core targets, and pathways was brought by the edge. DLT: Danlou tablet; I/R: ischemia/reperfusion; STRING: Search tool for the retrieval of interacting genes proteins; PPI: protein-protein interaction; DC: degree centrality.

Figure 3 Specific docking details between the top three core components and core proteins The green ribbon-like structures or grey surface structure displayed target proteins, the pink rod-like structures displayed chemical compounds, the purple rod-like structures displayed amino acid residues linking to the corresponding compounds, and the yellow dashed strip displayed connection distance between compounds and residues. A: quercetin (A1, MOL000098)-PTGS2 (PDB ID: 5IKV); B: quercetin (A1, MOL000098)-HSP90AA1 (PDB ID: 4EGK); C: quercetin (A1, MOL000098)-ESR1 (PDB ID: 4J24); D: luteolin (M2, MOL000006)-PTGS2 (PDB ID: 5IKV); E: luteolin (M2, MOL000006)-HSP90AA1 (PDB ID: 4EGK); F: luteolin (M2, MOL000006)-ESR1 (PDB ID: 4J24); G: baicalein (CS4, MOL002714)-PTGS2 (PDB ID: 5IKV); H: baicalein (CS4, MOL002714)-HSP90AA1 (PDB ID: 4EGK); I: baicalein (CS4, MOL002714)-ESR1 (PDB ID: 4J24). PTGS2: prostaglandin G/H synthase 2; HSP90AA1: heat shock protein HSP 90 alpha family class A member 1; ESR1: estrogen receptor 1.

Figure 4 Efficacy verification of 3 active compounds in DLT on the three core proteins in OGD/R-induced H9c2 cardiomyocytes A-C: the protective effects of the active compounds in DLT on cell viabilities in OGD/R injured H9c2 cells. The cell viabilities were detected by the CCK-8 assay. A: the effective range of Quercetin (A1, MOL000098) in OGD/R induced H9c2 cardiomyocytes, among which 20 μΜ concentration was applied to subsequent compound-pathway exploration. B: the effective range of Luteolin (M2, MOL000006) in OGD/R induced H9c2 cardiomyocytes, among which 10 μΜ concentration was applied to subsequent compound-pathway exploration. C: the effective range of Baicalein (CS4, MOL002714) in OGD/R induced H9c2 cardiomyocytes, among which 5 μΜ concentration was applied to subsequent compound-pathway exploration. D-G: Expression of PTGS2, HSP90AA1, and ESR1 were detected by Western blot, after intervention with Quercetin (20 μM), Luteolin (10 μM), or Baicalein (5 μM). D: representative images of bands detected by Western blot. E: expression of PTGS2 were detected by Western blot, after intervention with Quercetin (20 μM), Luteolin (10 μM), or Baicalein (5 μM). F: expression of HSP90AA1 were detected by Western blot, after intervention with Quercetin (20 μM), Luteolin (10 μM), or Baicalein (5 μM). G: expression of ESR1 were detected by Western blot, after intervention with Quercetin (20 μM), Luteolin (10 μM), or Baicalein (5 μM). DLT: Danlou tablet; OGD/R: oxygen-glucose deprivation/recovery; CCK-8: cell counting kit-8. PTGS2: prostaglandin G/H synthase 2; HSP90AA1: heat shock protein HSP 90 alpha family class A member 1; ESR1: estrogen receptor 1. Data are expressed as the mean ± standard deviation (n = 3). aP < 0.001 vs the control group; bP < 0.001, cP < 0.05, dP < 0.01, vs the OGD/R group.