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大渊饮汤通过抑制补体激活、LPS-TLR4/NF-κB 信号通路和 NET 形成来缓解溃疡性结肠炎。

Da-yuan-yin decoction alleviates ulcerative colitis by inhibiting complement activation, LPS-TLR4/NF-κB signaling pathway and NET formation.

机构信息

College of Pharmaceutical Science, Soochow University, Suzhou, 215123, China.

Suzhou Vocational Health College, Suzhou, 215009, China.

出版信息

J Ethnopharmacol. 2024 Oct 5;332:118392. doi: 10.1016/j.jep.2024.118392. Epub 2024 May 25.

DOI:10.1016/j.jep.2024.118392
PMID:38797378
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Da-yuan-yin decoction (DYY) is a classical traditional Chinese medicine prescription for ulcerative colitis (UC).

AIM OF STUDY

This study explored the protective effects and mechanisms of DYY on UC.

MATERIALS AND METHODS

The mice were fed 2.5% dextran sulfate sodium (DSS) for 7 days to establish UC. On the second day, DYY (0.4 g/kg, 0.8 g/kg, 1.6 g/kg) was orally administered daily for 7 consecutive days. The colon tissues and serum were measured by histopathological examination and biochemical analysis.

RESULTS

DYY significantly reduced the disease activity index (DAI) and severity of colon shortening and alleviated pathological changes in the colon tissue. DYY restored the protein expression of intestinal tight junction (TJ) protein (ZO-1, occludin and claudin-3). DYY remarkably decreased the level of lipopolysaccharide (LPS), Lactic acid (LA), circulating free DNA (cfDNA), complement (C3, C3a, C3c, C3aR1, C5a and C5aR1) and regulated the levels of inflammatory cytokines in serum. DYY significantly inhibited the expressions of nuclear factor kappa-B p65 (NF-κB p65) and Toll-like receptor 4 (TLR4), citrullinated histone H3 (CitH3) and myeloperoxidase (MPO), reactive oxygen species (ROS) peptidylarginine deiminase 4 (PAD4) and CD 11b, the mRNA levels of PADI4, MPO and ELANE in colon tissues.

CONCLUSIONS

DYY significantly attenuated DSS-induced UC, which was related with regulating the inflammatory response by the inhibition of complement activation, the LPS-TLR4/NF-κB signaling pathway and neutrophil extracellular traps (NETs) formation. DYY is a potential therapeutic agent for UC.

摘要

民族药理学相关性

大渊饮(DYY)是一种经典的溃疡性结肠炎(UC)的中药方剂。

目的

本研究探讨了 DYY 对 UC 的保护作用及其机制。

材料和方法

用 2.5%葡聚糖硫酸钠(DSS)喂养小鼠 7 天建立 UC。第二天,DYY(0.4g/kg、0.8g/kg、1.6g/kg)每日口服给药 7 天。通过组织病理学检查和生化分析测量结肠组织和血清。

结果

DYY 显著降低疾病活动指数(DAI)和结肠缩短的严重程度,并缓解结肠组织的病理变化。DYY 恢复了肠道紧密连接(TJ)蛋白(ZO-1、occludin 和 claudin-3)的蛋白表达。DYY 显著降低了内毒素(LPS)、乳酸(LA)、循环游离 DNA(cfDNA)、补体(C3、C3a、C3c、C3aR1、C5a 和 C5aR1)的水平,并调节了血清中炎症细胞因子的水平。DYY 显著抑制了核因子 kappa-B p65(NF-κB p65)和 Toll 样受体 4(TLR4)、瓜氨酸化组蛋白 H3(CitH3)和髓过氧化物酶(MPO)、活性氧物质(ROS)肽酰精氨酸脱氨酶 4(PAD4)和 CD11b 的表达,以及结肠组织中 PADI4、MPO 和 ELANE 的 mRNA 水平。

结论

DYY 显著减轻了 DSS 诱导的 UC,这与通过抑制补体激活、LPS-TLR4/NF-κB 信号通路和中性粒细胞胞外陷阱(NETs)形成来调节炎症反应有关。DYY 是 UC 的一种潜在治疗药物。

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