2,3,5,4 '-Tetrahydroxystilbene-2-O-beta-D-glucoside alleviated the acute hepatotoxicity and DNA damage in diethylnitrosamine-contaminated mice
2,3,5,4 '-Tetrahydroxystilbene-2-O-beta-D-glucoside alleviated the acute hepatotoxicity and DNA damage in diethylnitrosamine-contaminated mice
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2,3,5,4α-四羟基芪-2-O-β-d-葡萄糖苷减轻二乙基亚硝胺污染小鼠的急性肝毒性和DNA损伤
DOI：
10.1016/j.lfs.2020.117274
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发表时间：
2020
期刊：
影响因子：
6.1
通讯作者：
Hai Chunxu
中科院分区：
文献类型：
--
作者：
Yu Weihua;Zhao Jiuzhou;Li Wenli;Zheng Yipeng;Zhu Jingpu;Liu Jiangzheng;Liu Rui;Wang Zhao;Wang Xin;Hai Chunxu
目的2，3，5，4′-四羟基二苯乙烯-2-O-β-d-葡萄糖苷（TSG）是从何首乌中提取的关键活性成分。药理学研究表明，它发挥了许多生物学作用，包括抗氧化，抗衰老和抗炎。本研究旨在探讨TSG对二乙基亚硝胺（DEN）所致小鼠急性肝损伤和DNA损伤的影响，主要方法将50只雄性C57 BL/6小鼠随机分为5组（n= 10）：对照组、DEN组、DEN+TSG（低）组、DEN+ TSG（高）组和TSG（高）组。腹腔注射DEN（100 mg/kg），单独或与TSG（30或60 mg/kg，i. p.）关键发现TSG抑制DEN治疗小鼠的肝损伤和炎性细胞浸润。它还减弱了DEN诱导的活性氧（ROS）、促炎细胞因子和DNA损伤的积累。此外，TSG通过促进核红细胞2相关因子2（Nrf 2）蛋白磷酸化和核转位，促进Nrf 2靶抗氧化基因的表达。细胞色素P450家族2亚家族E成员1（CYP 2 E1）和细胞色素P450 1亚家族A成员1（CYP 1A 1）是DEN代谢活化的主要Ⅰ相解毒酶。TSG可抑制DEN诱导的CYP 2 E1和CYP 1A 1的表达，提示TSG可通过调节Nrf 2相关的抗氧化系统和DEN的代谢活化来减轻DEN诱导的急性肝毒性。因此，TSG可能是一种很有前途的治疗DEN肝损伤的药物。
Aims2,3,5,4′-Tetrahydroxystilbene-2-O-β-d-glucoside (TSG) is the key bioactive ingredient extracted fromPolygonum multiflorumThumb. Pharmacological studies suggest that it exerts numerous biological effects, including anti-oxidant, anti-aging, and anti-inflammation. This study aimed at investigating the effect of TSG on diethylnitrosamine (DEN)-induced acute hepatotoxicity and DNA damage.Main methodsFifty male C57BL/6 mice were randomly divided into 5 groups (n= 10 each): control, DEN, DEN+TSG (low), DEN+TSG (high) and TSG (high) groups. DEN (100 mg/kg) was injected intraperitoneally (i.p.) alone or with TSG (30 or 60 mg/kg, i.p.) for 5 consecutive days.Key findingsTSG inhibited liver injury and inflammatory cell infiltration in DEN-treated mice. It also attenuated DEN-induced accumulation of reactive oxygen species (ROS), proinflammatory cytokines, and DNA damage. Moreover, TSG promoted the expression of nuclear erythroid 2-related factor 2 (Nrf2) target antioxidant genes by enhancing Nrf2 protein phosphorylation and nuclear translocation. As major phase I detoxification enzymes, cytochrome P450 family 2 subfamily E member 1 (CYP2E1) and cytochrome P450 1 subfamily A member 1 (CYP1A1) are responsible for the metabolic activation of DEN. We found that TSG administration inhibited CYP2E1 and CYP1A1 induction in DEN-treated mice.SignificanceThese results indicate that TSG can alleviate DEN-induced acute hepatotoxicity by modulating the Nrf2-related antioxidant system and metabolic activation of DEN. Therefore, TSG might be a promising medication for DEN-induced liver injury treatment.