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二氢杨梅素通过腺苷 5'-单磷酸激活蛋白激酶通路抑制铅诱导的小鼠认知障碍和炎症。

Dihydromyricetin Inhibits Lead-Induced Cognitive Impairments and Inflammation by the Adenosine 5'-Monophosphate-Activated Protein Kinase Pathway in Mice.

机构信息

School of Life Science , Jiangsu Normal University , No.101, Shanghai Road , Tangshan New Area, 221116 , Xuzhou City , Jiangsu Province , PR China.

School of Chemistry and Pharmaceutica Engineering , Sichuan University of Science and Engineering , Xuyuan road , 643000 , Zigong City , Sichuan Province , PR China.

出版信息

J Agric Food Chem. 2018 Aug 1;66(30):7975-7982. doi: 10.1021/acs.jafc.8b02433. Epub 2018 Jul 19.

DOI:10.1021/acs.jafc.8b02433
PMID:29975840
Abstract

Dihydromyricetin (DHM), a natural flavonoid derived from the medicinal and edible plant Ampelopsis grossedentata, exhibits antioxidant, antiapoptosis, antitumor, and anti-inflammatory bioactivities. This study evaluated the effects of DHM on Pb-induced neurotoxicity and explored the underlying mechanisms. DHM significantly ameliorated behavioral impairments of Pb-induced mice. It decreased the levels of lipid peroxidation and protein carbonyl and increased the activities of superoxide dismutase and catalase in the brains. DHM suppressed Pb-induced apoptosis, as indicated by the decreased levels of Bax and cleaved caspase-3. DHM also decreased inflammatory cytokines in the brains of Pb-treated mice. DHM decreased amyloid-beta (Aβ) level and nuclear factor-κB nuclear translocation. Moreover, DHM induced the adenosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation and inhibited the activation of p38, Toll-like receptor 4, myeloid differentiation factor 88, and glycogen synthase kinase-3. Collectively, this is the first report indicating that DHM could improve Pb-induced cognitive functional impairment by preventing oxidative stress, apoptosis, and inflammation and that the protective effect was mediated partly through the AMPK pathway.

摘要

二氢杨梅素(DHM)是一种从药用和食用植物蛇葡萄中提取的天然黄酮类化合物,具有抗氧化、抗细胞凋亡、抗肿瘤和抗炎等生物活性。本研究评价了 DHM 对铅诱导的神经毒性的影响,并探讨了其潜在机制。DHM 显著改善了铅诱导的小鼠的行为障碍。它降低了大脑中脂质过氧化和蛋白质羰基的水平,增加了超氧化物歧化酶和过氧化氢酶的活性。DHM 抑制了铅诱导的细胞凋亡,表现为 Bax 和 cleaved caspase-3 水平降低。DHM 还降低了铅处理小鼠大脑中的炎症细胞因子。DHM 降低了淀粉样蛋白-β(Aβ)水平和核因子-κB 核转位。此外,DHM 诱导了腺苷 5'-单磷酸激活蛋白激酶(AMPK)磷酸化,并抑制了 p38、Toll 样受体 4、髓样分化因子 88 和糖原合酶激酶-3 的激活。总之,这是第一项表明 DHM 可以通过预防氧化应激、细胞凋亡和炎症改善铅诱导的认知功能障碍的报告,其保护作用部分是通过 AMPK 途径介导的。

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