Exploring the Mechanism of Astragalus propinquus Schischkin and Panax Notoginseng (A&P) Compounds in the Treatment of Renal Fibrosis and Chronic Kidney Disease Based on Integrated Network Analysis

Figures

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  Figure 1. Flowchart of investigation on the mechanism of A&P in the treatment of renal fibrosis in chronic kidney disease. First, the potential active components and targets were obtained from TCMSP and Target Prediction database. Second, CKD-related microarrays on NCBI were used to obtain disease-related targets. The intersection of active ingredient targets and disease targets is regarded as a common target. Thirdly, Go and KEGG enrichment analyses were performed for common targets. The differences of common targets were analyzed and visualized; heatmap was made. Cytoscape is used to construct the regulatory network of TCM. Then, UUO model was constructed to verify the hub gene and determine the effects of A&P. PyMOL is used for molecular docking of potentially active components and hub genes.

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  Figure 2. Schematic diagram of network pharmacology analysis. (a) Network Pharmacology. (b) Venn diagram of drug-disease common targets.

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  Figure 3. GO and KEGG enrichment of drug-disease common targets. (a) Biological process. (b) Molecular function. (c) Cellular component. (d) KEGG enrichment analysis.

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  Figure 4. Analysis of network pharmacology and differential analysis. (a) Regulatory network of TCM compound prescription (note: blue represents the potential active component of Panax notoginseng; Purple represents Cambrian; red represents Astragalus membranaceus; green stands for Achyranthes bidentata; yellow represents the core gene.). (b) Differential gene analysis of disease-targets by microarrays.

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  Figure 5. Effects of AP on renal injuries in UUO kidneys. (a) HE staining and Masson staining of mouse kidneys (scale bar = 100 μm). (b) Immunohistochemical staining of α-SMA in mouse kidneys (scale bar = 50 μm). ∗∗∗P < 0.001 with the indicated group.

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  Figure 6. Hub genes' verification. (a) Effect of AP on the protein level of HSF1, and RELA was detected by western blotting analysis. (b) Effect of AP on mRNA expression of α-SMA, FN, HSF1, and RELA according to real-time PCR analysis. ∗P < 0.05 and ∗∗∗P < 0.001 with the indicated group.

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  Figure 7. Molecular docking of some potential active ingredients and hub genes. (a) The interaction of RELA and indicated active ingredients. (b) The interaction of HSF1 and indicated active ingredients.