Exploring the Therapeutic Mechanism of Tingli Dazao Xiefei Decoction on Heart Failure Based on Network Pharmacology and Experimental Study

Figure 1. Venn diagram of TDXD targets and HF targets.

Figure 2. Network of active compounds-disease targets. Green regular triangle nodes represent the Tinglizi and Dazao. Purple round nodes represent the active components of TDXD. Red inverted triangle node represents HF. Yellow rhombic nodes represent the gene targets.

Figure 3. The PPI network of overlapping targets. Circular nodes represent the gene targets; the darker the node color and the larger the graph, the greater the degree value. Black lines represent the interaction between nodes, and the thicker the line, the closer the connection.

Figure 4. Enrichment analysis of TDXD against HF: (a) GO analysis of overlapping targets. The figure lists the top 10 GO pathways in each category. (b) Top 20 pathways of KEGG enrichment analysis. Bubble size represents the number of genes in this pathway, and the color reflects the −log10 (P value). (c) Compounds-targets-pathways network. Purple round nodes represent the active components of TDXD. Yellow rhombic nodes represent the gene targets. Green inverted triangle nodes represent the signaling pathways.

Figure 5. Molecular docking structure diagram. (a) IL-6-quercetin, (b) IL-6-kaempferol, (c) IL-6-isorhamnetin, (d) IL-6-beta-sitosterol, (e) VEGFA-quercetin, (f) VEGFA-kaempferol, (g) VEGFA-isorhamnetin, (h) VEGFA-beta-sitosterol, (i) TNF-quercetin, (j) TNF-kaempferol, (k) TNF-isorhamnetin, (l) TNF-beta-sitosterol, (m) AKT1-quercetin, (n) AKT1-kaempferol, (o) AKT1-isorhamnetin, (p) AKT1-beta-sitosterol, (q) MAPK1-quercetin, (r) MAPK1-kaempferol, (s) MAPK1-isorhamnetin, and (t) MAPK1-beta-sitosterol.

Figure 6. TDXD improved cardiac function in rats with HF. (a) Representative echocardiography images in each group, (b) EF%, (c) FS%, (d) LVIDd, and (e) LVIDs, n = 5. (f) Representative pictures of whole heart in each group, (g) HW/BW, n = 5. (h–j) Serum BNP, LDH, and CK-MB levels, n = 5. ∗P < 0.05 vs. sham group, #P < 0.05 vs. model group, ▲P > 0.05 vs. captopril group, and ΔP < 0.05 vs. captopril group.

Figure 7. TDXD reduced myocardial fibrosis in rats with HF. (a) Representative images of H&E staining in different groups, n = 5. Scale bar: 3 mm/200 μm. (b) Representative images of Masson staining in different groups, n = 5. Scale bar: 3 mm/200 μm. (c) Quantitative analysis of the myocardial fibrosis area, n = 5. ∗ < 0.05 vs. sham group, #P < 0.05 vs. model group, and ▲P > 0.05 vs. captopril group.

Figure 8. TDXD inhibited apoptosis and reduced the level of inflammatory cytokines. (a) Representative images of TUNEL staining in different groups, scale bar: 20 μm. (b) Quantitative analysis of TUNEL-positive, n = 3. (c–e) Representative western blotting pictures and quantitative analysis of Bcl-2 and Bax, n = 5. (f–h) Serum IL-6, IL-1β, and TNF-α levels, n = 5. ∗P < 0.05 vs. sham group, #P < 0.05 vs. model group, ▲P > 0.05 vs. captopril group, and ΔP < 0.05 vs. captopril group.

Figure 9. TDXD inhibited the activation of PI3K/AKT and MAPK signaling pathways. (a–d) Representative western blotting pictures and quantitative analysis of PI3K, p-Akt/AKT, and p-MAPK/MAPK, n = 5. ∗P < 0.05 vs. sham group, #P < 0.05 vs. model group, ▲P > 0.05 vs. captopril group, and ΔP < 0.05 vs. captopril group.