Mechanism Underlying the Action of Berberine in the Treatment of Gouty Arthritis Based on Network Pharmacology

Abstract

Introduction: Gouty arthritis (GA) is induced by a purine metabolism disorder and monosodium urate (MSU) crystal-related inflammation. Berberine (BBR), extracted from Coptis chinensis, ameliorates MSU-induced GA. However, the mechanisms of BBR against GA remain to be fully elucidated. This study aimed to identify the key targets and pathways mediating the effects of BBR against GA using network pharmacology. Methods: BBR and GA targets were obtained from several databases, and the network of BBR-GA common targets was visualized using Cytoscape software. Protein–protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the STRING and Database for Annotation, Visualization, and Integrated Discovery databases, respectively. Animal experiments were performed to determine the outcomes of the BBB intervention. The serum levels of IL-1β, IL-8, and IL-6 were detected using enzyme-linked immunosorbent assay. Results: Thirty-three common targets (including NF-κB, RelA, MAPK1, IL-6, and IL-1β) of BBR and GA were identified, and a network of common targets between BBR and GA was constructed. PPI analysis demonstrated that IL-1β, IL-6, TNF, MAPK, and RelA are key targets with high degree values. GO and KEGG pathway analyses revealed the involvement of inflammation-related biological processes and signaling pathways, such as the NF-κB, MAPK, and TNF signaling pathways. Animal experiments demonstrated that the uric acid, IL-1β, IL-6, and IL-8 serum levels were significantly lower in the BBR group compared with those in hyperuricemic rats. Conclusions: Using systematic network analysis, potential targets mediating the effects of BBR on GA were detected. The pathways and inflammatory factors involved were identified using in vivo experiments, thus providing a reference for further basic research and clinical applications of BBR in the treatment of GA.