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通过转录组分析发现,膳食槲皮素通过多种可能的途径缓解了 DSS 诱导的小鼠结肠炎。

Dietary Quercetin Alleviated DSS-induced Colitis in Mice Through Several Possible Pathways by Transcriptome Analysis.

机构信息

State Key Laboratory of Animal Nutrition, College of Animal Science & Technology, China Agricultural University, Beijing, China.

出版信息

Curr Pharm Biotechnol. 2020;21(15):1666-1673. doi: 10.2174/1389201021666200711152726.

Abstract

BACKGROUND

The prevalence of inflammatory bowel disease is rapidly increasing around the world. Quercetin is a flavonoid commonly found in vegetables and fruits and has been reported to exert numerous pharmacological activities such as enhancing antioxidant capacity or suppressing inflammation.

OBJECTIVE

We aimed to explore whether quercetin was effective for IBD and the underlying mechanism of quercetin for the ameliorative effects on the DSS-induced colitis in mice.

METHODS

Thirty-six mice were randomly assigned to three treatments, including the control group (Ctr), DSS-induced colitis group (DSS) and DSS-induced colitis supplemented with 500 ppm quercetin (DQ500). Colitis was induced by DSS intake, and body weight was recorded every day. After six days administration of DSS, intestinal permeability was measured, and the liver was taken for antioxidant enzyme tests. Colonic tissue was taken for the histopathlogical score and RNA-sequencing analysis.

RESULTS

In this experiment, dietary quercetin for 500ppm alleviated the DSS-induced colitis, possibly by strengthening intestinal integrity, liver antioxidant capacity. Based on the results of the transcriptome of colon tissue, several key genes were modulated by quercetin. ERK1/2-FKBP pathway and RXR-STAT3 pathway were involved in the development of IBD, furthermore, in the down-regulation of S100a8/9, FBN2 contributed to lowering the risk of colongenesis.

CONCLUSION

We demonstrated that dietary quercetin alleviated the DSS-induced colitis in mice. This is most likely due to its beneficial effects on intestinal integrity and modulation of several key pathways. Based on our research, quercetin was a promising candidate for IBD and its pharmaceutical effects on both IBD and colongenesis need further research.

摘要

背景

炎症性肠病在全球范围内的患病率正在迅速上升。槲皮素是一种常见于蔬菜和水果中的类黄酮,据报道具有多种药理活性,如增强抗氧化能力或抑制炎症。

目的

我们旨在探讨槲皮素是否对 IBD 有效,以及槲皮素改善 DSS 诱导的小鼠结肠炎的作用机制。

方法

36 只小鼠随机分为三组,包括对照组(Ctr)、DSS 诱导的结肠炎组(DSS)和 DSS 诱导的结肠炎补充 500ppm 槲皮素组(DQ500)。通过 DSS 摄入诱导结肠炎,每天记录体重。DSS 给药六天后,测量肠道通透性,并取肝脏进行抗氧化酶试验。取结肠组织进行组织病理学评分和 RNA 测序分析。

结果

在本实验中,饮食中添加 500ppm 的槲皮素可缓解 DSS 诱导的结肠炎,可能是通过增强肠道完整性和肝脏抗氧化能力。基于结肠组织转录组的结果,槲皮素调节了几个关键基因。ERK1/2-FKBP 通路和 RXR-STAT3 通路参与了 IBD 的发生,此外,S100a8/9 的下调,FBN2 有助于降低结肠发生的风险。

结论

我们证明了饮食中添加槲皮素可缓解 DSS 诱导的小鼠结肠炎。这很可能是由于其对肠道完整性的有益作用以及对几个关键通路的调节。基于我们的研究,槲皮素是 IBD 的有前途的候选药物,其对 IBD 和结肠发生的药物作用需要进一步研究。

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