Objective To investigate the potential gout treatment mechanisms and targets of Erythropalum scandens Bl. through network pharmacology and molecular docking techniques and experimental validatio based on ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry (UPLC-QE-Orbitrap-MS).
Methods The constituents of Erythropalum scandens Bl. were analysed by UPLC-QE-Orbitrap-MS, and the targets of the active ingredients were obtained using the online database SwissTargetPrediction, and the targets of gout-related diseases were screened out by GeneCards database. The String database and Cytoscape 3.7.2 software were used to construct the protein-protein interaction (PPI) network diagram and the active ingredient-target-pathway visualization and regulation network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the common targets using the DAVID database and the Weishengxin-Online Bioinformatics Analysis, as well as Visualization Cloud Platform. The AutoDock Tools 1.5.6 software was used to validate the molecular docking of the core targets and their corresponding compounds, and the predicted results were verified by animal experiments.
Results UPLC-QE-Orbitrap-MS analysis showed that 75 components were identified from Erythropalum scandens Bl., among which 69 components were reported for the first time in Erythropalum scandens Bl. The main categories of these components included fatty acyls, terpenoids, sugars and glycosides, phenylpropanoids, organic acids and their derivatives, amino acids and their derivatives, nucleotides and their derivatives, and phenols, etc. From the database, 806 active ingredient targets and 2, 358 disease targets were screened, resulting in 270 drug-disease intersection targets. and the PPI network diagram showed that STAT3, SRC, TP53, EGFR, AKT1, TNF, HSP90AA1, JUN and ERB2, etc., were the key targets. The results of the GO and KEGG enrichment analyses showed that the anti-gout effects of Erythropalum scandens Bl. might be related to PI3K/AKT, apoptosis, metabolic anti-inflammatory and other related signaling pathways. The molecular docking results of 10 core targets and their corresponding compounds showed that the docked proteins had a better binding energy. In vivo experiments confirmed that the aqueous extract of Erythropalum scandens Bl. could regulate serum uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN), and 24-hour urinary protein levels in mice with uric acid nephropathy. Additionally, it ameliorated renal tissue damage and apoptosis while modulating key proteins in the PI3K/AKT signaling pathway of mice.
Conclusion Erythropalum scandens Bl. contains abundant chemical components, which may exert anti-gout effects through key targets such as STAT3 and signaling pathways such as PI3K/AKT. Additionally, the aqueous extract of Erythropalum scandens Bl. can alleviate renal damage in mice with urate nephropathy.
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