First Clinical Medical College, Yunnan University of Chinese Medicine, Kunming, China.
School of Basic Medical Sciences, Yunnan University of Chinese Medicine, Kunming, China.
Medicine (Baltimore). 2023 Nov 24;102(47):e35973. doi: 10.1097/MD.0000000000035973.
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-α) 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-α, 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.
背景：桂枝芍药知母汤（GSZD）是一种中药方剂。既往研究表明，GSZD 可改善痛风性关节炎患者的临床症状和实验室指标。然而，既往研究尚未评估和分析其疗效、安全性、潜在机制以及与中药相关成分和痛风靶点之间的关系。
方法：检索来自多个数据库的 GSZD 治疗痛风性关节炎的随机对照试验。采用 Stata 17 软件进行荟萃分析。Galbraith 图用于寻找可能存在异质性的研究。Egger 检验和漏斗图评估发表偏倚。中药的相关成分和中药及痛风靶点从 TCMSP、HERB 和 DrugBank 等多个数据库中获得。通过 STRING 平台进行蛋白质-蛋白质相互作用网络分析。使用 DAVID 数据库进行 GO 和 KEGG 分析。通过 AutoDock 和 PyMOL 软件进行分子对接和对接结果的可视化。
结果：纳入 20 项研究，共 1633 例患者。荟萃分析表明，GSZD 可更好地提高临床疗效和视觉模拟评分，降低血尿酸和炎症生物标志物（包括 C 反应蛋白、红细胞沉降率、白细胞介素 6、白细胞介素 8 和肿瘤坏死因子-α）水平，优于常规治疗。此外，我们还检索到 157 种活性化合物、517 种草药靶基因、3082 种疾病靶标和 295 种草药和疾病的交集靶标。网络药理学分析结果显示，核心相关成分包括槲皮素、山奈酚、谷甾醇、木犀草素、儿茶素等。核心交集靶标包含 AKT1、TNF-α、TP53、IL6 等。关键信号通路包括 IL-17、HIF-1、TNF、PI3K-Akt 等。在 56 个分子对接结果中，仅有 8 个结果的结合能值大于-5.0 kcal/mol。
结论：GSZD 可能是治疗痛风性关节炎的一种满意的补充和替代疗法。但需要进一步研究验证。未来的痛风性关节炎研究可从β-谷甾醇和谷甾醇等活性成分、TNF-1、IL1B 和 ESR1 等靶标以及 IL-17 和 HIF-1 等信号通路进行。
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