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当药-α-D-吡喃葡萄糖基-(2→1)-α-D-吡喃葡萄糖苷通过调节炎症、过度增殖和抗氧化作用改善二乙基亚硝胺诱导的临床前阶段肝脏癌前病变的发展。

Umbelliferon-α-d-glucopyranosyl-(2→1)-α-Dglucopyranoside ameliorates Diethylnitrosamine induced precancerous lesion development in liver via regulation of inflammation, hyperproliferation and antioxidant at pre-clinical stage.

机构信息

Natural Product Drug Discovery Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, 211007, Uttar Pradesh, India.

Centre for Advanced Research in Pharmaceutical Sciences, Microbial and Pharmaceutical Biotechnology Laboratory, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.

出版信息

Biomed Pharmacother. 2017 Oct;94:834-842. doi: 10.1016/j.biopha.2017.07.047. Epub 2017 Aug 10.

DOI:10.1016/j.biopha.2017.07.047
PMID:28802237
Abstract

It is well documented that anomalous production of inflammatory proteins linked with most of the toxic expression and genesis of diverse chronic disease including cancer. Diethylnitrosamine (DEN) a well-known hepatotoxin and hepatocarcinogen, can induce oxidative stress and inflammatory reaction in it. Umbelliferone, secondary metabolites, is present in different plants and widely consumed by humans as medicine and food supplements. The aim of the current study was to scrutinize the chemoprotective potential of umbelliferon-α-d-glucopyranosyl-(2→1)-α-d-glucopyranoside (UFD) against DEN-induced hepatocellular carcinoma (HCC) in experimental rats. Single intraperitoneal injection of DEN (200mg/kg) was used for induction of HCC in rats and rats were grouped and orally treated with UFD (5, 10 and 20mg/kg) dose for 22 weeks. Parameters under investigation included hepatic, non-hepatic enzymes, oxidative stress, pro-inflammatory cytokines, COX-2 and NF-κB level along with histopathological examination in HCC rats. UFD exerted protective effect via reduction of oxidative stress, liver and non-liver parameters in a dose-dependent manner. It also reduced the expression of TNF-α, IL-1β, IL-6 and COX-2 in diseased rats. Our result revealed the essential repression of the inflammation cascade through modulation of nuclear factor-kappa B (NF-κB) signaling pathway.

摘要

有大量文献记载,与大多数毒性表达和多种慢性疾病(包括癌症)的发生有关的炎症蛋白异常产生。二乙基亚硝胺(DEN)是一种众所周知的肝毒素和肝癌致癌物,可在其中诱导氧化应激和炎症反应。伞形酮,次生代谢物,存在于不同的植物中,被人类广泛用作药物和食品补充剂。本研究旨在探讨伞形酮-α-d-吡喃葡萄糖基-(2→1)-α-d-吡喃葡萄糖苷(UFD)对实验大鼠 DEN 诱导的肝细胞癌(HCC)的化学预防潜力。单次腹腔注射 DEN(200mg/kg)用于诱导大鼠 HCC,将大鼠分组并口服 UFD(5、10 和 20mg/kg)治疗 22 周。研究参数包括 HCC 大鼠的肝、非肝酶、氧化应激、促炎细胞因子、COX-2 和 NF-κB 水平以及组织病理学检查。UFD 通过降低氧化应激、肝和非肝参数,以剂量依赖的方式发挥保护作用。它还降低了患病大鼠中 TNF-α、IL-1β、IL-6 和 COX-2 的表达。我们的结果表明,通过调节核因子-κB(NF-κB)信号通路,炎症级联反应受到了重要抑制。

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