Explore the action mechanism of Danggui Buxue decoction on chronic heart failure in rats by proteomics and untargeted metabolomics

Figures

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  Fig. 1. DBD can improve CHF accompanied by liver injury induced by ISO (A) The changes in body weight in all groups. (B) H&E staining of rat myocardium (40 × ). (C) Cardiac index evaluation. (D) Cardiac hypertrophy evaluation. (E) BNP level of serum in all groups. (F) AST levels in all groups. (G) ALT levels in all groups. ***P < 0.01 vs. control, ##P < 0.05, ###P < 0.01 vs. model,‾x ± standard error of mean (SEM); n = 8.

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  Fig. 2. TMT-labeled quantitative proteomic analysis of CHF rats (A-C) The volcano plot of the differential proteins. (A) Model vs. control. (B) DBD-H vs. model. (C) DBD-L + Positive vs. model. (D–F) GO enrichment analysis of proteomics. (D) Model vs. control. (E) DBD-H vs. model. (F) DBD-L + Positive vs. model. The horizontal coordinate is the enrichment terms, and the vertical coordinate is the number of mapped proteins. Cellular Component (CC) annotation information is green. Molecular Function (MF) annotation information is blue. Biological Process (BP) annotation information is red. (G–I) Subcellular localization analysis pie chart. (G) Model vs. control. (H) DBD-H vs. model. (I) DBD-L + Positive vs. model. (J–L) KEGG metabolic pathway enrichment analysis bubble diagram. (J) Model vs. control. (K) DBD-H vs. model. (L) DBD-L + Positive vs. model. The horizontal axis of the graph indicates the degree of enrichment, the vertical axis shows KEGG pathway information, the size of the circle represents the number of differentially expressed proteins mapped to the corresponding pathway, and the color indicates the significance of the P value.

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  Fig. 3. OPLS-DA results for QC samples (A) OPLS-DA score graph of QC samples in positive ion mode. (B) OPLS-DA score graph of QC samples in negative ion mode. (C) DBD-H vs. model. (D) DBD-L + Positive vs. model. The horizontal coordinate t 1O represented the first principal component prediction score, indicating the inter-group differences of the samples. The vertical coordinate t 1O represented the orthogonal scores, showing the within-group differences of the samples.

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  Fig. 4. Metabolomics analysis of liver tissue in CHF rats (A-B) Volcano map of differential metabolites screening. (A) DBD-H vs. model. (B) DBD-L + Positive vs. model. The upregulated metabolites were red bubbles, and the downregulated metabolites were blue bubbles. (C–D) Hierarchical Cluster Analysis Heat Map. (C) DBD-H vs. model. (D) DBD-L + Positive vs. model. The differential metabolites at the corresponding positions were displayed in different color blocks. Red represented an up-regulation, and blue represented a down-regulation in protein expression. Red color indicated relative higher concentration, while blue meant relative lower concentration levels. (E–F) Graph of differential abundance analysis of KEGG pathway. (E) DBD-H vs. model. (F) DBD-L + Positive vs. model.

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  Fig. 5. The levels of CAT, GSH-Px, and MDA in the serum and myocardial tissue of rats (A-B) MDA levels in serum and myocardial tissues. (C–D) CAT levels in serum and myocardial tissues. (E–F) GSH-Px levels in serum and myocardial tissues. ‾x ± SEM; n = 6; ***P < 0.01 vs. control, ##P < 0.05, ###P < 0.01 vs. model.

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  Fig. 6. Myocardial ATP content, COX and SDH viability measurements (A) ATP content in myocardium. (B) COX content in myocardium. (C) SDH content in myocardium. x‾± SEM; n = 6; ***P < 0.01 vs. control, ##P < 0.05, ###P < 0.01 vs. model.

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  Fig. 7. The expression of AMPK, pAMPK, SIRT1, PGC-1α, and PPAR β proteins in the myocardial tissues of CHF rats was upregulated by DBD (A) The expression of AMPK, pAMPK, SIRT1, PGC-1α, and PPARβ proteins was determined by Western blot. (B) AMPK level was upregulated by DBD. (C) pAMPK level was upregulated by DBD. (D) SIRT1 level was upregulated by DBD. (E) PGC-1α level was upregulated by DBD. (F) PPARβ level was upregulated by DBD. x‾ ± SEM; n = 4; ***P < 0.01 vs. control, ##P < 0.05, ###P < 0.01 vs. model.