Network pharmacology and experimental evaluation of Sanwei Tanxiang Tangsan in doxorubicin-induced heart failure

Fig. 1. Drug–component–target network of Mongolian medicine Sanwei Tanxiang Tangsan (STX). Network diagram constructed in Cytoscape 3.7.1 showing the interactions between the active components of STX and the common targets related to heart failure. Green diamonds represent the intersecting target genes. Light green nodes (TX1–TX3) denote active components from Santalum album, blue nodes (GZ1–GZ8) denote components from Choerospondias axillaris, and red nodes (RDK1–RDK7) denote components from Myristica fragrans. The purple node (A) represents β-sitosterol, the shared component between Choerospondias axillaris and Myristica fragrans. The density of edges reflects the complexity of interactions between components and targets. This network represents predicted interactions based on database-derived information and does not imply direct biological validation

Fig. 2. Protein–protein interaction (PPI) network and core hub genes of the common targets of STX in heart failure. (A) Global PPI network of the 153 overlapping targets obtained from the STRING database (confidence score ≥ 0.4) and visualized in Cytoscape 3.7.1. Node color depth from yellow to dark red indicates increasing degree value (number of interactions). (B) Subnetwork of the top hub genes screened by degree value, including AKT1, TP53, TNF, IL6, IL1B, PTGS2, CASP3, ESR1, JUN, and BCL2, illustrating the close connectivity among core regulatory targets. These hub genes are identified based on network topology and may represent general regulatory nodes rather than disease-specific targets

Fig. 3. Gene Ontology (GO) enrichment analysis of the common targets of STX and heart failure. Bar chart displaying the top enriched GO terms in three categories: biological process (BP, green), cellular component (CC, orange), and molecular function (MF, blue). The x-axis shows representative GO terms, and the y-axis indicates the percentage of genes annotated to each term. The results highlight enrichment in processes related to regulation of gene expression, apoptosis, response to external stimuli, endosomal and perinuclear localization, and protein binding–related functions. These enrichment results reflect functional associations and do not establish direct mechanistic relationships

Fig. 4. KEGG pathway enrichment analysis of the common targets of STX in heart failure. Bubble plot of the top enriched KEGG pathways. The x-axis represents the percentage of genes involved in each pathway, and bubble size reflects the gene count. The color scale corresponds to –log10(P value), with warmer colors indicating higher statistical significance. Enriched pathways include “Pathways in cancer”, “Lipid and atherosclerosis”, “AGE–RAGE signaling pathway in diabetic complications”, “Fluid shear stress and atherosclerosis”, TNF and IL-17 signaling pathways, HIF-1 signaling, and other inflammation- and apoptosis-related pathways. These pathways are derived from enrichment analysis and should be interpreted as potential biological associations rather than confirmed signaling mechanisms

Fig. 5. Representative echocardiographic M-mode images of left ventricular function in each experimental group. (A) Control (Con) group. (B) Doxorubicin-induced heart failure model (Mod) group. (C) Mongolian medicine Sanwei Tanxiang Tangsan (STX) treatment group. (D) Sacubitril/valsartan (ARNI) treatment group. LVDd and LVDs indicate left ventricular end-diastolic and end-systolic diameters, respectively. These images correspond to the quantitative echocardiographic parameters summarized in Table 3. Although representative images are shown, no statistically significant differences in EF and FS were observed between the STX or ARNI groups and the Model group

Fig. 6. Masson’s trichrome staining of myocardial tissue in each experimental group. Representative myocardial sections stained with Masson’s trichrome (collagen fibers in blue, muscle fibers in red) from (A) Control (Con) group, (B) Model (Mod) group, (C) STX group, and (D) ARNI group (original magnification ×400). The Mod group shows extensive blue collagen deposition and disrupted myocardial architecture, indicating severe myocardial fibrosis. Both STX and ARNI treatment groups exhibit reduced collagen fiber accumulation and improved myocardial structural integrity compared with the Mod group. These observations are qualitative, as quantitative assessment of fibrosis was not performed