Clinical efficacy evaluation and potential mechanism prediction on Guizhi-Shaoyao-Zhimu decoction in the treatment of gouty arthritis based on meta-analysis, network pharmacology analysis, and molecular docking

Background:Guizhi-Shaoyao-Zhimu decoction (GSZD) is a Chinese herb formula. Previous studies have reported that the clinical symptoms and laboratory indicators of gouty arthritis patients could be improved by GSZD. However, no previous study has evaluated and analyzed its efficacy, safety, underlying mechanisms, and the relationship between related ingredients of herbs and targets of gouty arthritis.Methods:Randomized controlled trials of GSZD for gouty arthritis were retrieved from various databases. Meta-analysis was performed by Stata 17 software. Galbraith plot was used to find studies with possible heterogeneity. Publication bias was assessed by Egger test and funnel plot. The related ingredients of herbs and the targets of herbs and gouty arthritis were obtained from several databases, such as TCMSP, HERB, and DrugBank. The protein-protein interaction network was conducted by the STRING platform. DAVID database was used to perform GO and KEGG analysis. Molecular docking and visualization of docking results were carried out by AutoDock and PyMOL software.Results:Twenty studies with 1633 patients were included. Meta-analysis indicated that GSZD could better improve the clinical efficiency and visual analogue scale score, and reduce the level of blood uric acid and inflammatory biomarkers (including C-reactive protein, erythrocyte sedimentation rate, interleukin 6, interleukin 8, and tumor necrosis factor-alpha) than conventional treatment. In addition, we retrieved 157 active compounds, 517 herb target genes, 3082 disease targets, and 295 intersection targets of herb and disease. The results of network pharmacology analysis showed that the core related ingredients included quercetin, kaempferol, sitosterol, luteolin, catechin, etc. The core intersection targets contained AKT1, TNF-alpha, TP53, IL6, etc. And the critical signaling pathways included IL-17, HIF-1, TNF, PI3K-Akt, etc. Among the 56 molecular docking results, only 8 results had binding energy values greater than -5.0 kcal/mol.Conclusion:GSZD could be a satisfactory complementary and alternative therapy for treating gouty arthritis. However, it should be verified by further studies. Future research on gouty arthritis could be conducted from the active components including beta-sitosterol and sitosterol, the targets including TNF-1, IL1B, and ESR1, and the signaling pathways including IL-17 and HIF-1.