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复方杜仲片通过抑制大鼠关节炎炎症和肠道微生物群紊乱来减轻佐剂性类风湿性关节炎。

Fufang Duzheng tablet attenuates adjuvant rheumatoid arthritis by inhibiting arthritis inflammation and gut microbiota disturbance in rats.

作者信息

Zhao Liming, Liu Meilin, Zheng Kai, Xiao Qiang, Yuan Lin, Wu Chuanfang, Bao Jinku

机构信息

Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610065, Sichuan, China.

Hubei Key Laboratory of Biological Resources Protection and Utilization, Hubei Minzu University, 445000, Enshi, China.

出版信息

Heliyon. 2024 Jun 7;10(12):e32705. doi: 10.1016/j.heliyon.2024.e32705. eCollection 2024 Jun 30.

Abstract

OBJECTIVE

To explore the treatment effect and potential mechanism on gut microbiota, nutrition, and metabolism of Fufang Duzheng Tablet (DZGP) on rheumatoid arthritis (RA).

METHODS

Collagen-induced arthritis rats' models were established and divided into three groups: model control group (FK), DZGP group (FZ, 0.45 g/kg/d), and methotrexate group (FM, 1.35 mg/kg), which were treated by gavage for 28 days. The physiopathologic changes of joints and body weight in each group were recorded; the morphology of synovial and ankle tissues was observed by hematoxylin-eosin staining, and the level of serum TNF-α and IL-1β was tested by ELISA. UPLC/MS-MS and network pharmacological analysis were used to identify the serum components, and 16S rDNA sequencing analysis was applied to the intestinal contents of rats.

RESULTS

DZGP treatment significantly alleviated arthritis symptoms, pathological manifestations, toe thickness, and TNF-α and IL-1β levels in RA rats. We identified 105 metabolites and 18 components in the serum of DZGP-group rats. The main therapeutic targets of DZGP for anti-RA were TP53, epidermal growth factor receptor, and AKT1. Molecular docking showed that there was good binding efficiency between core components and main targets. 16S rDNA sequencing showed that DZGP treatment regulated the structure of the gut microbiota.

CONCLUSION

DZGP showed a good anti-inflammatory effect on RA and played an important role in improving the structure of the gut microbiota in RA rats.

摘要

目的

探讨复方杜仲片(DZGP)对类风湿关节炎(RA)肠道微生物群、营养及代谢的治疗作用和潜在机制。

方法

建立胶原诱导性关节炎大鼠模型,分为三组:模型对照组(FK)、DZGP组(FZ,0.45 g/kg/d)和甲氨蝶呤组(FM,1.35 mg/kg),灌胃给药28天。记录各组关节的生理病理变化和体重;采用苏木精-伊红染色观察滑膜和踝关节组织形态,酶联免疫吸附测定法检测血清肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)水平。采用超高效液相色谱/质谱联用(UPLC/MS-MS)和网络药理学分析鉴定血清成分,并对大鼠肠道内容物进行16S核糖体DNA(rDNA)测序分析。

结果

DZGP治疗显著减轻RA大鼠的关节炎症状、病理表现、足趾厚度以及TNF-α和IL-1β水平。我们鉴定出DZGP组大鼠血清中的105种代谢物和18种成分。DZGP抗RA的主要治疗靶点为TP53、表皮生长因子受体和蛋白激酶B1(AKT1)。分子对接显示核心成分与主要靶点之间具有良好的结合效率。16S rDNA测序表明DZGP治疗可调节肠道微生物群的结构。

结论

DZGP对RA具有良好的抗炎作用,对改善RA大鼠肠道微生物群结构发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b70/11341321/dc90ad3c2b8f/gr1.jpg

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