College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China; Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, Hangzhou, 310053, China.
J Ethnopharmacol. 2023 Nov 15;316:116736. doi: 10.1016/j.jep.2023.116736. Epub 2023 Jun 5.
Qu-zhuo-tong-bi decoction (QZTBD) is a classic Chinese herbal medicine that has shown therapeutic efficacy in clinical practice against hyperuricemia and gout. However, the potential mechanisms of QZTBD remain poorly investigated.
To assess the therapeutic effects of QZTBD on hyperuricemia and gout and to reveal its mechanisms of action.
A Uox-KO mouse model of hyperuricemia and gout was established, and QZTBD was administered at a dosage of 18.0 g/kg/d. Throughout the experimental period, the effects of QZTBD on gout symptoms were monitored and analyzed. The integrated network pharmacology and gut microbiota analysis strategy was conducted to explore the mechanism of QZTBD in the treatment of hyperuricemia and gout. Targeted metabolomic analysis was performed to investigate the variation of amino acids and Spearman's rank correlation analysis was conducted to reveal the relationship between the discrepant bacterial genera and the altered amino acid. Flow cytometry was utilized to analysis the proportion of Th17 and Treg cells, and the production of pro-inflammatory cytokines was measured by ELISA. qRT-PCR and Western blot assay were applied to detect the expression of mRNA and protein respectively. Autodock vina 1.1.2 was used to evaluate the docking interactions.
QZTBD treatment showed remarkable efficacy against hyperuricemia and gout with respect to attenuation of disease activity metrics through gut microbiome recovery and intestinal immune homeostasis. The administration of QZTBD significantly elevated the abundance of Allobaculum and Candidatus sacchairmonas, corrected the aberrant amino acid patterns, repaired the impaired intestinal barrier, restored the balance of Th17/Treg cells via PI3K-AKT-mTOR pathway, and reduced the levels of inflammatory cytokines such as IL-1β, IL-6, TNF-α and IL-17. Fecal microbiota transplantation from QZTBD treated mice demonstrated convincing evidence of efficacy and mechanism of QZTBD.
Taken together, our study explores the therapeutic mechanism of an effective herbal formula, QZTBD, for gout treatment through remodeling gut microbiome and regulating the differentiation of CD4 T cells via PI3K-AKT-mTOR pathway.
祛浊通痹汤（QZTBD）是一种经典的中药方剂，在临床上已被证明对高尿酸血症和痛风具有治疗效果。然而，其潜在的作用机制仍未得到充分研究。
评估 QZTBD 对高尿酸血症和痛风的治疗作用，并揭示其作用机制。
建立 Uox-KO 小鼠高尿酸血症和痛风模型，给予 QZTBD 剂量为 18.0 g/kg/d。在整个实验过程中，监测和分析 QZTBD 对痛风症状的影响。采用整合网络药理学和肠道微生物组分析策略，探讨 QZTBD 治疗高尿酸血症和痛风的作用机制。进行靶向代谢组学分析，研究氨基酸的变化，并进行 Spearman 秩相关分析，以揭示差异细菌属与改变的氨基酸之间的关系。采用流式细胞术分析 Th17 和 Treg 细胞的比例，通过 ELISA 测定促炎细胞因子的产生。采用 qRT-PCR 和 Western blot 检测 mRNA 和蛋白的表达。使用 Autodock vina 1.1.2 评估对接相互作用。
QZTBD 治疗对高尿酸血症和痛风具有显著疗效，可通过肠道微生物组恢复和肠道免疫稳态来减轻疾病活动指标。QZTBD 给药显著增加了 Allobaculum 和 Candidatus sacchairmonas 的丰度，纠正了异常的氨基酸模式，修复了受损的肠道屏障，通过 PI3K-AKT-mTOR 通路恢复了 Th17/Treg 细胞的平衡，并降低了 IL-1β、IL-6、TNF-α 和 IL-17 等炎症细胞因子的水平。来自 QZTBD 治疗小鼠的粪便微生物群移植提供了令人信服的证据，证明了 QZTBD 的疗效和机制。
综上所述，本研究通过重塑肠道微生物群和调节 CD4 T 细胞分化来探索有效中药方剂 QZTBD 治疗痛风的治疗机制，通过 PI3K-AKT-mTOR 通路。
