Indirubin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice through the inhibition of inflammation and the induction of Foxp3-expressing regulatory T cells
Indirubin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice through the inhibition of inflammation and the induction of Foxp3-expressing regulatory T cells
复制标题
DOI：
10.1016/j.acthis.2016.06.004
复制
发表时间：
2016-01-01
影响因子：
2.5
通讯作者：
Gong, Yang
中科院分区：
文献类型：
--
作者：
Gao, Wenyan;Guo, Yufang;Gong, Yang
靛玉红是中药当归龙回丸的有效成分，具有广泛的抗癌、抗炎作用。然而，靛玉红对溃疡性结肠炎（UC）的影响尚未得到解决。本文研究了靛玉红对葡聚糖硫酸钠（DSS）诱导的小鼠UC的治疗作用及其机制。以3%DSS饮水连续7 d，诱导BALB/c小鼠UC模型。靛玉红（10 mg/kg）治疗7 d可明显抑制体重减轻，逆转疾病活动指数（DAI）升高，减轻隐窝变形和粘膜损伤，减少结肠粘膜炎性细胞浸润，从而改善DSS诱导的UC。靛玉红治疗后结肠组织中肿瘤坏死因子（TNF）-α、干扰素（IFN）-γ、白细胞介素（IL）-2水平及髓过氧化物酶（MPO）活性均显著降低，而IL-4和IL-10水平显著升高。此外，靛玉红给药有效抑制DSS诱导的UC小鼠结肠中的CD 4（+）T细胞浸润，并促进表达Foxp 3的调节性T细胞的产生。此外，进一步的研究表明靛玉红明显抑制DSS诱导的核因子（NF）-κ B信号通路的激活。这些结果表明靛玉红的显著抗UC作用可能归因于其抑制炎症反应和促进Foxp 3（+）T细胞。我们的研究为靛玉红的抗UC作用及其相关分子机制提供了第一个证据，并为UC治疗提供了一个有希望的候选药物。(C)2016 Elsevier GmbH. All rights reserved.
Indirubin, an active ingredient of a traditional Chinese medicine prescription named Danggui Longhui Wan, has been reported to exhibit abroad anti-cancer and anti-inflammation activities. However, the effect of indirubin on ulcerative colitis (UC) has not been addressed. Here, we investigated the therapeutic efficacy of indirubin on dextran sulfate sodium (DSS)-induced UC in mice and explored its underlying mechanisms. UC model was induced in BALB/c mice by administrating with 3% DSS in drinking water for 7 days. Subsequently, indirubin treatment (10 mg/kg) for 7 days obviously inhibited the loss of body weight, reversed the elevation of disease activity index (DAI), alleviated crypt distortion and mucosal injury, and reduced inflammatory cell infiltration in the colon mucosa, thereby ameliorating DSS-induced UC. Mechanically, the levels of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and interleukin (IL)-2 as well as myeloperoxidase (MPO) activity in colon tissues were decreased significantly, while the levels of IL-4 and IL-10 were increased remarkably by indirubin treatment. Moreover, indirubin administration effectively suppressed CD4(+) T cell infiltration in the colon of DSS-induced UC mice and promoted the generation of Foxp3-expressing regulatory T cells. Additionally, further studies showed that indirubin obviously inhibited DSS-induced activation of nuclear factor (NF)-kappa B signaling. These results reveal that the significant anti-UC effect of indirubin may be attributable to its inhibition of inflammatory responses and promotion of Foxp3(+) T cells. Our studies provide the first evidence for the anti-UC effect of indirubin as well as the related molecular mechanisms and suggest a promising candidate drug for UC therapy. (C) 2016 Elsevier GmbH. All rights reserved.