Discussion on the Potential Mechanism of Wuling Decoction in the Treatment of Uric Acid Nephropathy based on Network Pharmacology.

INTRODUCTION

Uric acid nephropathy (UAN) poses a significant threat to human health, and conventional drug treatments often cause adverse reactions. This study aimed to elucidate the potential mechanism of Wuling Decoction (WLD) in ameliorating UAN, integrating network pharmacology prediction with experimental validation.

METHODS

Active components and targets of WLD were identified using the TCMSP and Target Prediction databases. UAN-related targets were sourced from GeneCards and OMIM. Key networks (active ingredient-target, PPI) were constructed using Cytoscape 3.9 and StringDB, followed by network topology analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of potential WLD-UAN targets were performed via DAVID and visualized using a bioinformatics platform. Molecular docking of core targets with key active ingredients was conducted using AutoDock Vina. Key findings were further validated in animal models of UAN.

RESULTS

We identified 50 active WLD components and 124 potential targets for UAN intervention. Core active ingredients included Alisol B, Alisol B 23-acetate, 16alpha-Hydroxydehydrotrametenolic acid, Dehydrotumulosic acid, Polyporenic acid C, Cerevisterol, and (22e,24r)-Ergosta- 6-en-3beta,5alpha,6beta-triol. Critical targets were MMP2, IGF1R, SRC, PIK3CA, and ESR1. GO enrichment yielded 467 significant terms, while KEGG analysis identified 132 pathways, predominantly involving cancer, endocrine resistance, and the AGE-RAGE signaling pathway in diabetic complications. Strong binding affinity was confirmed between the 7 key ingredients and 5 core targets via molecular docking. Animal experiments corroborated these network pharmacology predictions.

DISCUSSION: Our results demonstrate that WLD's therapeutic effect on UAN likely involves the modulation of multiple targets (MMP2, IGF1R, SRC, PIK3CA, ESR1) and pathways, notably cancer- related and endocrine resistance pathways, alongside AGE-RAGE signaling. This multi-target action aligns with traditional Chinese medicine principles. While animal validation supports the predictions, limitations include the need for further in vitro functional studies and clinical validation.

CONCLUSION

WLD ameliorates UAN primarily by downregulating MMP2, IGF1R, SRC, PIK3- CA, and ESR1 proteins. This integrated approach reveals the systemic mechanism of WLD, offering a scientific foundation for its clinical application and highlighting its potential as a multi-target therapeutic strategy for UAN.