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吴茱萸碱通过调节 NF-κB 和 NLRP3 炎性小体预防葡聚糖硫酸钠诱导的小鼠实验性结肠炎。

Evodiamine prevents dextran sulfate sodium-induced murine experimental colitis via the regulation of NF-κB and NLRP3 inflammasome.

机构信息

College of Veterinary Medicine, Jilin University, Changchun, 130062, People's Republic of China.

College of Veterinary Medicine, Jilin University, Changchun, 130062, People's Republic of China; Key laboratory for Zoonosis, Ministry of Education, Changchun, 130062, People's Republic of China.

出版信息

Biomed Pharmacother. 2019 Feb;110:786-795. doi: 10.1016/j.biopha.2018.12.033. Epub 2018 Dec 13.

DOI:10.1016/j.biopha.2018.12.033
PMID:30554117
Abstract

Evodiamine (EVO), an extraction from the traditional Chinese medicine Evodia rutaecarpa, has been reported to possess anti-inflammatory, anti-tumor and other pharmacological activities. However, the effectiveness of EVO to relieve dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) has not been evaluated. In this study, the protective effects and mechanisms of EVO on DSS-induced UC mice were investigated. The results indicated that treatment with EVO ameliorated DSS-induced UC mice body weight loss, disease activity index (DAI), colon length shortening, colonic pathological damage, and myeloperoxidase (MPO) activity. The production of TNF-α, IL-1β and IL-6 was also significantly inhibited by EVO. Further mechanistic results showed that EVO restrained the inflammation by regulating NF-κB signal and NLRP3 inflammasome. Furthermore, results also showed that EVO contributed to the tight junction (TJ) architecture integrity by modulating the expression of zonula occludens-1 (ZO-1) and occludin during colitis. Surprisingly, treatment with EVO reduced the concentration of plasmatic lipopolysaccharide (LPS) and re-balanced the levels of Escherichia coli and Lactobacillus. These findings suggested that EVO may have a potential protective effect on DSS-induced colitis and may be useful for the prevention and treatment of UC.

摘要

吴茱萸碱(EVO)是从传统中药吴茱萸中提取的一种物质,已被报道具有抗炎、抗肿瘤等多种药理活性。然而,EVO 缓解葡聚糖硫酸钠(DSS)诱导的溃疡性结肠炎(UC)的有效性尚未得到评估。在本研究中,研究了 EVO 对 DSS 诱导的 UC 小鼠的保护作用及其机制。结果表明,EVO 治疗可改善 DSS 诱导的 UC 小鼠体重减轻、疾病活动指数(DAI)、结肠缩短、结肠病理损伤和髓过氧化物酶(MPO)活性。EVO 还显著抑制 TNF-α、IL-1β 和 IL-6 的产生。进一步的机制研究结果表明,EVO 通过调节 NF-κB 信号和 NLRP3 炎性体来抑制炎症。此外,结果还表明,EVO 通过调节紧密连接(TJ)相关蛋白闭合蛋白-1(ZO-1)和闭锁蛋白的表达,有助于 TJ 结构的完整性,在结肠炎过程中。令人惊讶的是,EVO 的治疗降低了血浆脂多糖(LPS)的浓度,并重新平衡了大肠杆菌和乳酸杆菌的水平。这些发现表明,EVO 可能对 DSS 诱导的结肠炎具有潜在的保护作用,可用于预防和治疗 UC。

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