Exploring the mechanism of Jianpi Qushi Huayu Formula in the treatment of chronic glomerulonephritis based on network pharmacology
- 7 October 2021
- journal article
- Published by Springer Science and Business Media LLC in Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie
- Vol. 394 (12), 2451-2470
- https://doi.org/10.1007/s00210-021-02159-2
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.Keywords
Funding Information
- National Natural Science Foundation of China (No.81973546)
- Natural Science Foundation of Anhui Province (No.1808085MH276)
- Scientific Research Project of Inheritance and Innovation of Traditional Chinese Medicine of Anhui Province (No.2020ccyb08)
This publication has 47 references indexed in Scilit:
- Hypoxia, the HIF pathway and neutrophilic inflammatory responsesBiological Chemistry, 2013
- STRING v9.1: protein-protein interaction networks, with increased coverage and integrationNucleic Acids Research, 2012
- Sublytic C5b‐9 complexes induce proliferative changes of glomerular mesangial cells in rat Thy‐1 nephritis through TRAF6‐mediated PI3K‐dependent Akt1 activationThe Journal of Pathology, 2011
- Fast docking using the CHARMM force field with EADock DSSJournal of Computational Chemistry, 2011
- Chemokines in Renal InjuryJournal of the American Society of Nephrology, 2011
- The STRING database in 2011: functional interaction networks of proteins, globally integrated and scoredNucleic Acids Research, 2010
- The Nuclear Factor NF- B Pathway in InflammationCold Spring Harbor Perspectives in Biology, 2009
- Mechanisms of tubular volume retention in immune-mediated glomerulonephritisKidney International, 2009
- The role of chemokines in glomerulonephritisFrontiers in Bioscience-Landmark, 2008
- The Protein Data BankNucleic Acids Research, 2000