Exploring the Mechanism of Danshensu in the Treatment of Doxorubicin-Induced Cardiotoxicity Based on Network Pharmacology and Experimental Evaluation

Figure 1. Chemical structure of Danshensu.

Figure 2. Schematic diagram of the drug delivery protocol.

Figure 3. The intersection target (A) of heart damage and DOX and its quantitative expression (B). Among them, pink represents the target of heart damage, green represents the target of DOX, and brown represents its intersection.

Figure 4. The BP (A) related to oxidative stress, inflammation, and apoptosis were ranked according to the number of related targets and all the MF (B).

Figure 5. The PPI network (A) of intersecting targets is represented in (B), with color as the variable, and the size of the points is related to the degree value. The closer the color of the points and edges, the greater the importance, and the closer the color of the points and edges, the smaller the importance. All the targets related to Keap1 are sorted by the degree value (C).

Figure 6. Effect of DSS on the ECG of DOX-induced cardiac injury in mice. (A) Representative electrocardiograms of each group. Black arrows mark ST-segment elevation and red arrows mark QT interval. (B) Statistics of QTc interval for each group. Data are presented as the mean ± SEM (n = 3). **P < 0.01 vs. CON; #P < 0.05; and ##P < 0.01 vs. DOX.

Figure 7. Effects of DSS on pathological changes of cardiac tissue as surveyed by H&E staining. DSS on H&E staining in DOX-induced cardiotoxicity in mice. Scale bar = 50 μm (400×).

Figure 8. Effect of DSS on CK (A) and LDH (B) activities in DOX-induced cardiotoxicity in mice. Serum was collected from mice hearts of the CON, DOX, CAP, DSSL, DSSH, and DSS. Data are presented as the mean ± SEM (n = 10). **P < 0.01 vs. CON; #P < 0.05; and ##P < 0.01 vs. DOX.

Figure 9. Effect of DSS on the level of ROS in myocardial tissue. Scale bar = 100 μm (200×). The fluorescence intensity and area were expressed as a percentage. Statistics of ROS fluorescent area. Data are presented as the mean ± SEM (n = 6). **P < 0.01 vs. CON; #P < 0.05; and ##P < 0.01 vs. DOX.

Figure 10. Effect of DSS on MDA content (A), SOD (B), CAT (C), GPX (D) activities in DOX-induced cardiotoxicity in mice. Serum was collected from mice of the CON, DOX, DSS, DSSL, DSSH, and CAP. Data are presented as the mean ± SEM (n = 10, n=10). **P < 0.01 vs. CON; #P < 0.05; and ##P < 0.01 vs. DOX.

Figure 11. Effect of DSS on the levels of IL-6 (A) and TNF-α (B). Data are presented as the mean ± SEM (n = 6). **P < 0.01 vs. CON; ##P < 0.01 vs. DOX.

Figure 12. Effect of DSS on the protein expressions of BAX, BCL-2, and CASP3 (A). The band intensities of BAX/BCL-2 (B) and CASP3 (C) were normalized to β-actin. Data are presented as the mean ± SEM (n = 3). **P < 0.01 vs. CON; #P < 0.05; and ##P < 0.01 vs. DOX.