Natural dietary compound naringin prevents azoxymethane/dextran sodium sulfate-induced chronic colorectal inflammation and carcinogenesis in mice
Natural dietary compound naringin prevents azoxymethane/dextran sodium sulfate-induced chronic colorectal inflammation and carcinogenesis in mice
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天然膳食化合物柚皮苷可预防氧化偶氮甲烷/葡聚糖硫酸钠诱导的小鼠慢性结直肠炎症和癌变
DOI：
10.1080/15384047.2018.1453971
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发表时间：
2018-03
影响因子：
3.6
通讯作者：
Xian-Jun Qu
中科院分区：
文献类型：
--
作者：
Yu-Sheng Zhang;Feng Wang;Shu-Xiang Cui;Xian-Jun Qu
摘要柚皮苷是一种天然黄酮类化合物，富含于柑橘类水果中。我们的目的是评估柚皮苷对结肠炎和慢性炎症驱动的癌变的抑制作用。雄性C57 BL/6小鼠暴露于AOM/DSS以诱导结直肠炎症和致癌。口服柚皮苷可预防AOM/DSS诱导的溃疡性结肠炎和癌变，且无明显副作用。柚皮苷通过抑制结直肠组织中骨髓源性抑制细胞（MDSC）、促炎介质GM-CSF/M-CSF、IL-6和TNF-α以及NF-κB/IL-6/STAT 3级联反应减轻结肠炎和结直肠腺瘤的严重程度。柚苷处理的小鼠表现出正常的结直肠组织结构。电子显微镜分析表明，抑制强大的内质网（ER）应激诱导的自噬。柚皮苷可抑制结直肠粘膜细胞分泌内质网跨膜蛋白，如GRP 78、ATF 6、IRE 1 α和活化的PERK磷酸化eIF-2α以及自噬体复合物ATG 3、ATG 5、ATG 7、ATG 12、ATG 16和ATG 16 L1。结论：柚皮苷通过抑制结直肠粘膜细胞中ER应激诱导的自噬来预防结肠炎和结直肠癌的发生。柚皮苷可能成为预防溃疡性结肠炎和结直肠肿瘤的有效药物。
ABSTRACT Naringin, a natural occurring flavonoid compound, enriches in citrus fruits. We aimed to evaluate the inhibitory effect of naringin on colitis and chronic inflammation-driven carcinogenesis. Male C57BL/6 mice were exposed to AOM/DSS to induce colorectal inflammation and carcinogenesis. Naringin by oral administration prevented AOM/DSS-induced ulcerative colitis and carcinogenesis without significant side effects. Naringin attenuated the severity of colitis and colorectal adenomas through inhibiting myeloid-derived suppressor cells (MDSCs), pro-inflammatory mediators GM-CSF/M-CSF, IL-6 and TNF-α and the NF-κB/IL-6/STAT3 cascades in colorectal tissues. Naringin-treated mice exhibited normalized structures of colorectal tissues. Electron microscopy analysis showed the suppression of robust endoplasmic reticulum (ER) stress-induced autophagy. Naringin inhibited the secretion of the ER-spanning transmembrane proteins, such as GRP78 ATF6, IRE1α and activated PERK phosphorylated eIF-2α and complex of autophagosomes ATG3, ATG5, ATG7, ATG12, ATG16 and ATG16L1 in the colorectal mucosal cells. Conclusion: Naringin prevented colitis and colorectal carcinogenesis through suppressing robust ER stress-induced autophagy in colorectal mucosal cells. Naringin could develop a promising therapeutic agent for the prevention of ulcerative colitis and colorectal tumor.
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DOI：
10.1007/s13277-015-3774-7
发表时间：
2016-01
期刊：
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
影响因子：
--
作者：
Banjerdpongchai R;Wudtiwai B;Khaw-On P;Rachakhom W;Duangnil N;Kongtawelert P
通讯作者：
Kongtawelert P
影响因子：
3.6
作者：
Yu-sheng Zhang;Ye Li;Yan Wang;Shi-Yue Sun;Tao Jiang;Cong Li;S. Cui;Xian-Jun Qu
通讯作者：
Yu-sheng Zhang;Ye Li;Yan Wang;Shi-Yue Sun;Tao Jiang;Cong Li;S. Cui;Xian-Jun Qu
影响因子：
3.1
作者：
Kraus, Sarah;Sion, Daniel;Arber, Nadir
通讯作者：
Arber, Nadir
影响因子：
5.1
作者：
Chtourou, Yassine;Aouey, Bakhta;Fetoui, Hamadi
通讯作者：
Fetoui, Hamadi
DOI：
10.1177/0394632017711055
发表时间：
2017-06
影响因子：
3.5
作者：
Ma N;Liu Q;Hou L;Wang Y;Liu Z
通讯作者：
Liu Z