Mango polyphenolics reduce inflammation in intestinal colitis-involvement of the miR-126/PI3K/AKT/mTOR axis in vitro and in vivo.
Mango polyphenolics reduce inflammation in intestinal colitis-involvement of the miR-126/PI3K/AKT/mTOR axis in vitro and in vivo.
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DOI：
10.1002/mc.22484
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发表时间：
2017-01
影响因子：
4.6
通讯作者：
Mertens-Talcott, Susanne U.
中科院分区：
文献类型：
--
作者：
Kim, Hyemee;Banerjee, Nivedita;Barnes, Ryan C.;Pfent, Catherine M.;Talcott, Stephen T.;Dashwood, Roderick H.;Mertens-Talcott, Susanne U.
本研究旨在阐明芒果的抗炎作用机制。含没食子酸和没食子酸酯的多酚类化合物，以及miR-126/PI3K/AKT/mTOR信号轴在体内外的作用。从芒果中提取的多酚(var.在脂多糖(LPS)处理的CD-18Co细胞中进行了研究。大鼠接受含有芒果多酚的饮料或对照饮料，并暴露于3%葡聚糖硫酸钠(DSS)的三个周期中，然后进行2周的恢复期。芒果提取物(10mgGAE/L)可抑制脂多糖处理的CCD18Co细胞中NF-κB、p-NF-κB、PI3K(p85β)、HIF-1α、p70S6K1和RPS6的蛋白表达。脂多糖降低miR-126的表达，而芒果提取物以剂量依赖的方式诱导miR-126的表达。通过用芒果多酚逆转MI3K(P85β)拮抗剂处理细胞，证实了miR126与其靶标PI3K(P85 DNA)之间的关系。在体内，芒果饮料对DSS诱导的结肠炎症有保护作用(47%，P=0.05)，并降低了中央和基底部的Ki-67标记指数。芒果饮料能显著抑制促炎细胞因子α、IL-1mRNA和β的表达。此外，芒果处理降低了PI3K、AKT和mTOR的表达，而上调了miR-126的表达。这些结果表明，芒果多酚通过调节PI3K/AKT/mTOR途径减轻炎症反应，至少部分是通过上调体内和体外miRNA-126的表达来实现的；因此，芒果多酚可能与溃疡性结肠炎的预防有关。
This study sought to elucidate the mechanisms underlying the anti-inflammatory effect of mango (Mangifera Indica L.) polyphenolics containing gallic acid and gallotanins, and the role of the miR-126/PI3K/AKT/mTOR signaling axis in vitro and in vivo. Polyphenolics extracted from mango (var. Keitt) were investigated in lipopolysaccharide (LPS)-treated CCD-18Co cells. Rats received either a beverage with mango polyphenolics or a control beverage, and were exposed to three cycles of 3% dextran sodium sulfate (DSS) followed by a 2-wk recovery period. The mango extract (10 mg GAE/L) suppressed the protein expression of NF-κB, p-NF-κB, PI3K (p85β), HIF-1α, p70S6K1, and RPS6 in LPS-treated CCD-18Co cells. LPS reduced miR-126 expression, whereas, the mango extract induced miR-126 expression in a dose-dependent manner. The relationship between miR-126 and its target, PI3K (p85β), was confirmed by treating cells with miR-126 antagomiR where mango polyphenols reversed the effects of the antagomiR. In vivo, mango beverage protected against DSS-induced colonic inflammation (47%, P = 0.05) and decreased the Ki-67 labeling index in the central and basal regions compared to the control. Mango beverage significantly attenuated the expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and iNOS at the mRNA and protein level. Moreover, the expression of PI3K, AKT, and mTOR was reduced, whereas, miR-126 was upregulated by the mango treatment. These results suggest that mango polyphenols attenuated inflammatory response by modulating the PI3K/AKT/mTOR pathway at least in part through upregulation of miRNA-126 expression both in vitro and in vivo; thus, mango polyphenolics might be relevant as preventive agents in ulcerative colitis.
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影响因子：
5.8
作者：
Link, Alexander;Balaguer, Francesc;Goel, Ajay
通讯作者：
Goel, Ajay
影响因子：
3.7
作者：
Guo, Chunguang;Sah, Jerome F.;Beard, Lydia;Willson, James K. V.;Markowitz, Sanford D.;Guda, Kishore
通讯作者：
Guda, Kishore
DOI：
10.1158/1940-6207.capr-09-0117
发表时间：
2010-04
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Cui X;Jin Y;Hofseth AB;Pena E;Habiger J;Chumanevich A;Poudyal D;Nagarkatti M;Nagarkatti PS;Singh UP;Hofseth LJ
通讯作者：
Hofseth LJ
影响因子：
9.3
作者：
Garrido, G;González, D;Delgado, R
通讯作者：
Delgado, R
DOI：
10.1196/annals.1397.071
发表时间：
2007-01-01
期刊：
SIGNAL TRANSDUCTION PATHWAYS, PT D
影响因子：
--
作者：
Dos Santos, S.;Delattre, A.-I.;Raes, M.
通讯作者：
Raes, M.