Niaoduqing alleviates podocyte injury in high glucose model via regulating multiple targets and AGE/RAGE pathway: Network pharmacology and experimental validation

Abstract

Purpose: The aim of present study was to explore the pharmacological mechanisms of Niaoduqing granules on the treatment of podocyte injury in diabetic nephropathy (DN) via network pharmacology and experimental validation.Methods: Active ingredients and related targets of Niaoduqing, as well as related genes of podocyte injury, proteinuria and DN, were obtained from public databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network analysis were performed to investigate the potential mechanisms. High glucose (HG) -induced MPC5 cell injury model was treated with the major core active ingredients of Niaoduqing and used to validate the predicted targets and signaling pathways.Results: Totally, 16 potential therapeutic targets were identified by intersecting the targets of Niaoduqing and disease, in which 7 of them were considered as the core targets via PPI network analysis. KEGG enrichment analysis showed that AGE-RAGE signaling pathway was identified as the most crucial signaling pathway. The results of in vitro experiments revealed that the treatment of Niaoduqing active ingredients significantly protected MPC5 cells from HG-induced apoptosis. Moreover, Niaoduqing could significantly attenuate the HG-induced activation of AGE-RAGE signaling pathway, whereas inhibited the over-expression of VEGF-A, ICAM-1, PTGS-2 and ACE in HG-induced MPC5 cells.Conclusion: Niaoduqing might protect against podocyte injury in DN through regulating the activity of AGE/RAGE pathway and expression of multiple genes. Further clinical and animal experimental studies are necessary to confirm present findings.

Understanding Proteinuria in Patients with Diabetic Kidney Disease and Progress of Drug Therapy from a New Perspective

“…Niaoduqing granules can be used to effectively treat proteinuria in patients with DKD. Through network pharmacology, it has been found that the mechanism of Niaoduqing granules in treating DN proteinuria is to inhibit the activity of the AGE/RAGE pathway and the overexpression of VEGF-A, ICAM-2, PTGS-5, and ACE in MPC1 cells to prevent podocyte injury in DN [110]. However, evidence of adverse drug reactions remains unclear [111].…”

Bioinformatics led discovery of biomarkers related to immune infiltration in diabetes nephropathy

“…The increase of intracellular adhesion molecule-1 (ICAM-1), tumor necrosis factor (TNF), interleukin-1 and interleukin -6 and the infiltration and functional activity of macrophages, neutrophils, fibrosis and mast cell in the kidney and their functional activity are important driving factors of renal inflammation and fibrosis. [8][9][10] Over the past decade, many potential diagnostic markers have been discovered for this condition. [11] Serum TNF receptors 1 and 2 are significantly correlated with certain inflammation-related DN precocious glomerular lesion types.…”