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纳米颗粒姜黄素通过调节肠道微生物群和诱导调节性T细胞改善实验性结肠炎。

Nanoparticle curcumin ameliorates experimental colitis via modulation of gut microbiota and induction of regulatory T cells.

作者信息

Ohno Masashi, Nishida Atsushi, Sugitani Yoshihiko, Nishino Kyohei, Inatomi Osamu, Sugimoto Mitsushige, Kawahara Masahiro, Andoh Akira

机构信息

Department of Medicine, Shiga University of Medical Science, Otsu, Japan.

出版信息

PLoS One. 2017 Oct 6;12(10):e0185999. doi: 10.1371/journal.pone.0185999. eCollection 2017.

Abstract

BACKGROUND AND AIMS

Curcumin is a hydrophobic polyphenol derived from turmeric, a traditional Indian spice. Curcumin exhibits various biological functions, but its clinical application is limited due to its poor absorbability after oral administration. A newly developed nanoparticle curcumin shows improved absorbability in vivo. In this study, we examined the effects of nanoparticle curcumin (named Theracurmin) on experimental colitis in mice.

METHODS

BALB/c mice were fed with 3% dextran sulfate sodium (DSS) in water. Mucosal cytokine expression and lymphocyte subpopulation were analyzed by real-time PCR and flow cytometry, respectively. The profile of the gut microbiota was analyzed by real-time PCR.

RESULTS

Treatment with nanoparticle curcumin significantly attenuated body weight loss, disease activity index, histological colitis score and significantly improved mucosal permeability. Immunoblot analysis showed that NF-κB activation in colonic epithelial cells was significantly suppressed by treatment with nanoparticle curcumin. Mucosal mRNA expression of inflammatory mediators was significantly suppressed by treatment with nanoparticle curcumin. Treatment with nanoparticle curcumin increased the abundance of butyrate-producing bacteria and fecal butyrate level. This was accompanied by increased expansion of CD4+ Foxp3+ regulatory T cells and CD103+ CD8α- regulatory dendritic cells in the colonic mucosa.

CONCLUSIONS

Treatment with nanoparticle curcumin suppressed the development of DSS-induced colitis potentially via modulation of gut microbial structure. These responses were associated with induction of mucosal immune cells with regulatory properties. Nanoparticle curcumin is one of the promising candidates as a therapeutic option for the treatment of IBD.

摘要

背景与目的

姜黄素是一种从传统印度香料姜黄中提取的疏水性多酚。姜黄素具有多种生物学功能,但其临床应用因口服后吸收性差而受到限制。新开发的纳米姜黄素在体内表现出更好的吸收性。在本研究中,我们检测了纳米姜黄素(名为Theracurmin)对小鼠实验性结肠炎的影响。

方法

给BALB/c小鼠饮用含3%葡聚糖硫酸钠(DSS)的水。分别通过实时PCR和流式细胞术分析黏膜细胞因子表达和淋巴细胞亚群。通过实时PCR分析肠道微生物群的特征。

结果

纳米姜黄素治疗显著减轻体重减轻、疾病活动指数、组织学结肠炎评分,并显著改善黏膜通透性。免疫印迹分析表明,纳米姜黄素治疗可显著抑制结肠上皮细胞中的NF-κB激活。纳米姜黄素治疗可显著抑制炎症介质的黏膜mRNA表达。纳米姜黄素治疗增加了产丁酸细菌的丰度和粪便丁酸水平。这伴随着结肠黏膜中CD4+ Foxp3+调节性T细胞和CD103+ CD8α-调节性树突状细胞的扩增增加。

结论

纳米姜黄素治疗可能通过调节肠道微生物结构抑制DSS诱导的结肠炎的发展。这些反应与具有调节特性的黏膜免疫细胞的诱导有关。纳米姜黄素是治疗炎症性肠病的有前景的候选治疗药物之一。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f9c/5630155/33a5dd455f47/pone.0185999.g001.jpg

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