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桑葚果实对葡聚糖硫酸钠诱导的小鼠溃疡性结肠炎的预防作用及潜在机制

The preventive effect and underlying mechanism of Mill. fruits on dextran sulphate sodium-induced ulcerative colitis in mice.

作者信息

Zhang Yi, Wang Ou, Ma Nan, Yi Junjie, Mi Hongying, Cai Shengbao

机构信息

Faculty of Agriculture and Food, Yunnan Institute of Food Safety, Kunming University of Science and Technology, Kunming, Yunnan Province, 650500, People's Republic of China.

National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing, 100050, People's Republic of China.

出版信息

Food Funct. 2021 Oct 19;12(20):9965-9978. doi: 10.1039/d1fo01558c.

DOI:10.1039/d1fo01558c
PMID:34494061
Abstract

The purpose of this research was to explore the preventive effect of an 80% ethanol extract of Mill. fruits on dextran sulfate sodium (DSS)-induced colitis in mice and to elucidate the underlying molecular mechanisms of this effect. The results indicated that the extract, especially when administered at a high dose, could dramatically decrease the disease activity index, maintain normal spleen conditions, and improve colonic histopathology and length in the DSS-induced mice. In addition, extract administration could significantly suppress the levels of malondialdehyde, myeloperoxidase, tumor necrosis factor-α, interleukin-1β, and interleukin-6 and enhance superoxide dismutase and glutathione levels. The extract obviously protected intestinal barrier integrity by improving Occludin, ZO-1 and Claudin-1 expression levels. Western blot and immunohistochemistry analyses further indicated that the preventive effect of the phenol-rich extract on DSS-induced colitis might be achieved through the up-regulation of the expression of several pivotal oxidative stress-associated proteins, namely Nrf2, NQO1 and HO-1, and the down-regulation of the expression of several pivotal inflammation-associated proteins, namely -NF-κB, -IκB, COX-2, iNOS, -P38, -Erk1/2, and -JNK. Therefore, fruits extract possesses the capability to prevent DSS-induced ulcerative colitis in mice and could be utilized as a natural substance in the exploitation of functional foods as an adjuvant dietary therapy for preventing and/or alleviating inflammatory bowel disease.

摘要

本研究的目的是探讨磨盘草果实80%乙醇提取物对葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎的预防作用,并阐明其作用的潜在分子机制。结果表明,该提取物,尤其是高剂量给药时,可显著降低疾病活动指数,维持脾脏正常状态,并改善DSS诱导小鼠的结肠组织病理学和结肠长度。此外,给予提取物可显著抑制丙二醛、髓过氧化物酶、肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6的水平,并提高超氧化物歧化酶和谷胱甘肽水平。该提取物通过提高闭合蛋白、紧密连接蛋白1和Claudin-1的表达水平,明显保护肠道屏障完整性。蛋白质免疫印迹和免疫组织化学分析进一步表明,富含酚类的提取物对DSS诱导的结肠炎的预防作用可能是通过上调几种关键的氧化应激相关蛋白(即Nrf2、NQO1和HO-1)的表达,以及下调几种关键的炎症相关蛋白(即-NF-κB、-IκB、COX-2、iNOS、-P38、-Erk1/2和-JNK)的表达来实现的。因此,磨盘草果实提取物具有预防DSS诱导的小鼠溃疡性结肠炎的能力,可作为一种天然物质用于开发功能性食品,作为预防和/或缓解炎症性肠病的辅助饮食疗法。

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