Thymoquinone ameliorates diabetic phenotype in Diet-Induced Obesity mice via activation of SIRT-1-dependent pathways.
Thymoquinone ameliorates diabetic phenotype in Diet-Induced Obesity mice via activation of SIRT-1-dependent pathways.
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DOI：
10.1371/journal.pone.0185374
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Heart EA
中科院分区：
文献类型：
--
作者：
Karandrea S;Yin H;Liang X;Slitt AL;Heart EA
百里醌是一种天然存在的醌类化合物，是植物黑种草的主要生物活性成分，在细胞内发生氧化还原循环，将NADH再氧化为NAD+。通过口服葡萄糖和胰岛素耐量试验（OGTT和ITT）评估，TQ给药（20 mg/kg/bw/天）可降低饮食诱导肥胖（DIO）小鼠的空腹血糖和空腹胰岛素水平，从而降低其糖尿病表型，并改善葡萄糖耐量和胰岛素敏感性。此外，TQ降低血清胆固醇水平和肝脏甘油三酯，增加磷酸化Akt的蛋白表达，降低血清炎症标志物Akt n和MCP-1水平，降低NADH/NAD+比值。这些变化被肝脏中磷酸化SIRT-1和AMPKα以及骨骼肌中磷酸化SIRT-1的增加所证实。TQ还通过SIRT-1依赖性机制增加胰岛素抵抗HepG 2细胞的胰岛素敏感性。这些发现与TQ依赖性的NADH再氧化为NAD+一致，其刺激葡萄糖和脂肪酸氧化以及SIRT-1依赖性途径的激活。总之，这些结果表明TQ改善了2型糖尿病DIO小鼠模型中的糖尿病表型。
Thymoquinone, a natural occurring quinone and the main bioactive component of plant Nigella sativa, undergoes intracellular redox cycling and re-oxidizes NADH to NAD+. TQ administration (20 mg/kg/bw/day) to the Diet-Induced Obesity (DIO) mice reduced their diabetic phenotype by decreasing fasting blood glucose and fasting insulin levels, and improved glucose tolerance and insulin sensitivity as evaluated by oral glucose and insulin tolerance tests (OGTT and ITT). Furthermore, TQ decreased serum cholesterol levels and liver triglycerides, increased protein expression of phosphorylated Akt, decreased serum levels of inflammatory markers resistin and MCP-1, and decreased NADH/NAD+ ratio. These changes were paralleled by an increase in phosphorylated SIRT-1 and AMPKα in liver and phosphorylated SIRT-1 in skeletal muscle. TQ also increased insulin sensitivity in insulin-resistant HepG2 cells via a SIRT-1-dependent mechanism. These findings are consistent with the TQ-dependent re-oxidation of NADH to NAD+, which stimulates glucose and fatty acid oxidation and activation of SIRT-1-dependent pathways. Taken together, these results demonstrate that TQ ameliorates the diabetic phenotype in the DIO mouse model of type 2 diabetes.
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影响因子：
9.8
作者：
Bordone L;Motta MC;Picard F;Robinson A;Jhala US;Apfeld J;McDonagh T;Lemieux M;McBurney M;Szilvasi A;Easlon EJ;Lin SJ;Guarente L
通讯作者：
Guarente L
影响因子：
2.4
作者：
Fararh, KM;Shimizu, Y;Takewaki, T
通讯作者：
Takewaki, T
影响因子：
6.1
作者：
Pari, Leelavinothan;Sankaranarayanan, Chandrasekaran
通讯作者：
Sankaranarayanan, Chandrasekaran
影响因子：
168.9
作者：
Kahn, Steven E.;Cooper, Mark E.;Del Prato, Stefano
通讯作者：
Del Prato, Stefano
影响因子：
3.3
作者：
Fu, Zhuo;Gilbert, Elizabeth R.;Liu, Dongmin
通讯作者：
Liu, Dongmin