Apigenin prevents metabolic syndrome in high-fructose diet-fed mice by Keap1-Nrf2 pathway.
Apigenin prevents metabolic syndrome in high-fructose diet-fed mice by Keap1-Nrf2 pathway.
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DOI：
10.1016/j.biopha.2018.06.108
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发表时间：
2018-09
期刊：
影响因子：
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通讯作者：
Min Yang;Zhenhuan Jiang;Chenguang Li;Yanjuan Zhu;Zhu Li;Yunzhao Tang;C. Ni
中科院分区：
文献类型：
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作者：
Min Yang;Zhenhuan Jiang;Chenguang Li;Yanjuan Zhu;Zhu Li;Yunzhao Tang;C. Ni
长期高果糖饮食会导致各种不良代谢影响。芹菜素是一种天然存在的植物黄酮，在水果和蔬菜中含量丰富。本研究的目的是确定芹菜素对代谢综合征的保护作用，并阐明潜在的潜在机制。采用高果糖喂养4周建立动物模型。通过口服糖耐量试验和稳态模型评估-胰岛素抵抗指数来评估胰岛素抵抗。通过血清AST、ALT、肝组织病理学改变和肝内脂质蓄积来评价肝功能。以血清甘油三酯、总胆固醇、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇水平作为评价血脂变化的指标。芹菜素通过改善高果糖喂养小鼠的胰岛素抵抗、减轻肝损伤和抑制脂质代谢的改变而发挥有益的作用。此外，芹菜素有效地促进了Nrf2核转位的积累，并伴随着HO-1和NQO1蛋白表达的增加，这两个蛋白的表达有助于减轻氧化应激。分子对接结果表明，芹菜素与Keap1蛋白中Nrf2结合部位之间存在潜在的相互作用。综上所述，我们证明了芹菜素预防高果糖诱导的代谢综合征可能是通过抑制Keap1与Nrf2的结合，从而抑制Nrf2核转位，从而增加包括HO-1和NQO1在内的抗氧化基因的表达。
Chronic dietary high fructose leads to various kinds of undesirable metabolic effects. Apigenin, a naturally occurring plant flavone, is plentiful in fruits and vegetables. The aim of this study was to identify the protective effects of apigenin on metabolic syndrome and elucidate potential underlying mechanisms. The animal model was established by 4-weeks high fructose feeding. Insulin resistance was estimated by oral glucose tolerance test and homeostasis model assessment-insulin resistance index. Liver function was evaluated by serum AST and ALT, hepatic histopathological alternation, and lipid accumulation in the liver. The alterations of lipid profile was evaluated by TG, TC, LDL-C and HDL-C levels in serum. Administration of apigenin exerted beneficial effects through improving insulin resistance, alleviating liver injury, and inhibiting the alterations of lipid profile in high fructose-fed mice. In addition, apigenin potently facilitated the accumulation of Nrf2 nuclear translocation and accompanied by increasing HO-1 and NQO1 protein expressions, which are responsible for attenuating oxidative stress. Molecular docking results demonstrated that potential interaction of apigenin with the Nrf2-binding site in the Keap1 protein. In summary, we demonstrated that apigenin prevented high fructose-induced metabolic syndrome probably by inhibiting binding of Keap1 to Nrf2, and thus Nrf2 nuclear translocation, subsequently resulting in increased the expressions of anti-oxidative genes including HO-1 and NQO1.