Abstract
6′-O-Caffeoylarbutin (CA) is the most abundant compound found within Vaccinium dunalianum Wight, which is used as a traditional Chinese herbal tea for its effects in lowering uric acid and anti-rheumatoid arthritis. No reports to date, however, have explored the pharmacological impact of CA on inflammatory activity. In this study, the anti-inflammatory targets and molecular mechanisms of CA were evaluated through zebrafish inflammation model, network pharmacology and molecular docking. The results showed that CA was able to inhibit cyclooxygenase (COX-2/1) at a dose-dependent fashion in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated zebrafish. Network pharmacology analyses was employed to derive 156 putative CA-related anti-inflammatory targets, which were subjected to functional enrichment analyses to obtain 511 associated Gene Ontology (GO) terms and 180 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Moreover, 9 core targets (HRAS, SRC, MMP9, HSP90AA, CASP, ANXA5, EGFR, ESR1, and AKT1) associated with the anti-inflammatory effect of CA were further selected and identified based on network topology analyses and molecular docking. Overall, the results of this study suggest that CA exerts its anti-inflammatory effects through a complex mechanism of action, and these findings offer a robust foundation for future in-depth analyses exploring the pharmacological pathways through which CA can prevent rheumatoid arthritis-associated damage.
Published Version
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