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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Effect and Mechanisms of Huangqi-Shanzhuyu in the Treatment of Diabetic Nephropathy based on Network Pharmacology and In Vitro Experiments

Author(s): Yu Han*, Shufei Wei, Chao Liu, Ying Nie, Shizhao Yuan, Yinghua Ma, Yile Zhao and Guying Zhang

Volume 27, Issue 14, 2024

Published on: 10 October, 2023

Page: [2078 - 2089] Pages: 12

DOI: 10.2174/0113862073241153231003094411

Price: $65

Abstract

Background: Huangqi-Shanzhuyu (HS), a classic combination of Chinese herbal formulae, has been widely used for the treatment of diabetic nephropathy (DN). However, its pharmacological mechanism of action is still unclear.

Methods: The active ingredients of HS and their potential targets were identified through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the DN-related targets were determined from GeneCards, Online Mendelian Inheritance in Man (OMIM), PharmGkb, and Therapeutic Target Database (TTD). The Cytoscape software was used to construct a herb-disease-target network and screen core genes. STRING was employed to generate a protein-protein interaction (PPI) network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the mechanism of action of HS in DN. Animal experiments and molecular docking were used to verify the potential mechanism.

Results: In total, 40 active ingredients and 180 effective targets of HS in DN were identified and 1115 DN-related targets were retrieved. From the PPI network, VEGFA, AKT1, IL6, IL1B, TP53, MMP9, PTGS2, CASP3, EGF and EGFR were identified as core genes. The anti-DN mechanism mainly involved multiple signaling pathways such as AGEs-RAGE. Animal experiments and molecular docking analysis confirmed that HS downregulated the expression of IL-1 and IL-6 via kaempferol-mediated inhibition of JNK1 phosphorylation.

Conclusion: HS exhibits a therapeutic effect in DN through its multiple ingredients that act on several targets and multiple signaling pathways, including AGEs-RAGE.

Keywords: Huangqi shanzhuyu, diabetic nephropathy, molecular docking, JNK, OMIM, TTD.

Graphical Abstract
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