Anti-cystitis glandularis action exerted by glycyrrhetinic acid: bioinformatics analysis and molecular validation

Cystitis glandularis (CG) is a chronic hyperplastic disorder of the bladder, and the available clinical drug therapy is insufficient currently. Glycyrrhetinic acid (GA), a bioactive compound extracted from the roots of Glycyrrhiza glabra, is found with beneficial actions, including anti-inflammatory and anti-oxidative effects. We previously reported that GA relieves CG symptoms in animal model, implying the potential application of GA to treat CG. However, the action mechanisms of GA against CG remain unclear. In this study, we aimed to identify the pivotal targets and therapeutic effects of GA through integrated bioinformatics analysis and experimental validation. Integrated bioinformatics analysis screened eleven potential therapeutic targets for GA against CG, and seven pivotal targets were identified subsequently. Enrichment gene analysis revealed GA exhibiting biological activities against CG via regulating multiple pharmacological targets and molecular pathways associated with inflammatory reaction and oxidative stress. Molecular docking computation revealed potent affinity and interaction between GA and prostaglandin-endoperoxide synthase 2 (PTGS2) and mucin 1 (MUC1) proteins in CG. To validate biochemically, increased mRNA and protein expressions of PTGS2 and MUC1 were observed in human CG samples. Compared to CG mice, GA-treated CG mice exhibited reduced inflammatory cytokine contents and downregulated PTGS2 and MUC1 mRNA and protein levels. These integrated findings suggest the potential therapeutic effects of GA against CG via the regulation of targeting genes and pathways. However, further studies are necessary to perform and facilitate the clinical application of GA for treating CG.