Shexiang Baoxin Pills alleviate doxorubicin-induced cardiotoxicity via the reactive oxygen species-mediated AKT/Bcl-2 pathway

Figure 1.. Flowchart of the network pharmacology-based study.

Figure 2.. The potential function and pathways of SBP on DOX-induced cardiotoxicity. (A) Analyzing the network to unveil the active ingredients of each of the 7 components in SBP and their respective targets of action. (B) Genes present in both drug and disease. (C) PPI network diagram produced by STRING. (D) The main target network of SBP playing a role in DOX-induced cardiotoxicity. (E) Top 10 results of GO analysis including BP, GC, and molecular functions (MF). (F) Top 20 pathways of SBP acting on DOX-induced cardiotoxicity. BP = biological processes, CC = cellular composition, DOX = doxorubicin, MF = molecular functions, PPI = protein–protein interaction, SBP = Shexiang Baoxin Pills.

Figure 3.. SBP reduces DOX-induced apoptosis. (A) Cell viability was tested using the CCK-8 assay. DOX significantly attenuated H9c2 cell viability and SBP reversed the effect of DOX on H9c2 cell viability. (B) Representative groups of DCFH-DA and Hoechst images. (C) Plotting cell cycle statistical analysis showing that SBP attenuated DOX stimulation in H9c2 cells. (D) Cell cycle assays for each group are presented. (E) Apoptosis in each group detected by flow cytometry. (F) Plotting of apoptosis statistical analysis showing that SBP attenuated the apoptosis induced by DOX on H9c2. *P < .05, **P < .01, ***P < .001. DOX = doxorubicin, SBP = Shexiang Baoxin Pills.

Figure 4.. The prediction pathways of network pharmacology were validated by Western blot. (A) Western blot detection of AKT and p-AKT, BAX, Bcl-2 expression. (B) p-AKT/AKT was significantly decreased in the DOX group compared to the control group, and p-AKT/AKT was elevated with SBP compared to the DOX group. (C) BAX/Bcl-2 was significantly elevated in the DOX group compared to the control group, and BAX/Bcl-2 was significantly decreased after using SBP compared to the DOX group. *P < .05, **P < .01, ***P < .001. DOX = doxorubicin, SBP = Shexiang Baoxin Pills.