Abstract
This study was to explore the effective components, potential targets, and pathways of Jianpi Qushi Huayu Formula (JQHF) for the treatment of chronic glomerulonephritics (CGN). First, the Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), GeneCards, and OMIM databases were used to collect the major active components of JQHF and potential therapeutic targets of CGN. Then, functional enrichment analysis was performed to clarify the mechanisms of the JQHF on CGN. Subsequently, molecular docking was simulated to assess the binding ability of key targets and major active components. Finally, quantitative real-time PCR and western blot were performed for experimental verification of cells in vitro. A total of 55 active ingredients contained and 220 putative identified targets were screened from JQHF, of which 112 overlapped with the targets of CGN and were considered potential therapeutic targets. Then, we found quercetin and kaempferol are two key ingredients of JQHF, which may act on the top 10 screened targets of PPI, affecting CGN through related signal transduction pathways. Subsequently, molecular docking predicted that quercetin and kaempferol bind firm with the top 10 core targets of PPI. Further experiment verified some results and showed that JQHF has protected glomerular mesangial cells from lipopolysaccharide-induced inflammation by inhibiting expressions of IL6, TNF-α, and AKT1, and activating expressions of VEGFA. Based on network pharmacology, we explored the multi-component, multi-target, and multi-pathway characteristics of JQHF in treating CGN, and found that JQHF could act on IL6, TNF-α, VEGFA, and AKT1 to exert the effect of anti-CGN, which provided new ideas and methods for further research on the mechanism of JQHF in treating CGN.
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The data used and analyzed to support the findings of this study are available from the corresponding author upon request.
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Funding
This study was financially supported by the National Natural Science Foundation of China (No.81973546), the Natural Science Foundation of Anhui Province (No.1808085MH276), and the Scientific Research Project of Inheritance and Innovation of Traditional Chinese Medicine of Anhui Province (No.2020ccyb08).
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Tao Liu conceived and designed the study. Tao Liu and Ya Chen Gao wrote the paper. Jia Rong Gao and Xiu Juan Qin reviewed and edited the manuscript. All authors read and approved the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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Liu, T., Gao, Y.C., Qin, X.J. et al. Exploring the mechanism of Jianpi Qushi Huayu Formula in the treatment of chronic glomerulonephritis based on network pharmacology. Naunyn-Schmiedeberg's Arch Pharmacol 394, 2451–2470 (2021). https://doi.org/10.1007/s00210-021-02159-2
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DOI: https://doi.org/10.1007/s00210-021-02159-2