Arctigenin efficiently enhanced sedentary mice treadmill endurance.

Arctigenin efficiently enhanced sedentary mice treadmill endurance.
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DOI:
10.1371/journal.pone.0024224
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Shen X
Shen X
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Tang X;Zhuang J;Chen J;Yu L;Hu L;Jiang H;Shen X

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缺乏体力活动被认为是2型糖尿病和其他代谢性疾病的潜在危险因素之一,而耐力运动训练可以增强脂肪氧化,这与肥胖症的胰岛素敏感性改善有关。AMP激活的蛋白激酶(AMPK)作为一种能量传感器,在能量平衡的调节中起着关键作用,其激活可促进葡萄糖摄取、促进线粒体生物合成和糖酵解。最近的研究甚至表明,AMPK激活有助于在不运动的情况下增强耐力。本文报道了从传统中药牛蒡子中提取的天然产物牛蒡苷元。(菊科)在H9 C2和C2 C12细胞中强烈增加AMPK磷酸化并随后上调其下游途径。研究发现牛蒡子苷元通过钙调蛋白依赖性蛋白激酶激酶(CaMKK)和丝氨酸/苏氨酸激酶11(LKB 1)依赖性途径磷酸化AMPK。基于小鼠跑台的体内试验进一步表明,施用牛蒡子苷元有效地提高小鼠的耐力,如通过增加疲劳时间和距离所反映的,并且有效地增强肌肉组织中线粒体生物合成和脂肪酸氧化(FAO)相关基因的表达。因此,我们的研究结果表明,牛蒡子苷元可能被用作一个潜在的先导化合物,用于发现具有模拟运动训练作用的药物来治疗代谢性疾病。
Physical inactivity is considered as one of the potential risk factors for the development of type 2 diabetes and other metabolic diseases, while endurance exercise training could enhance fat oxidation that is associated with insulin sensitivity improvement in obesity. AMP-activated protein kinase (AMPK) as an energy sensor plays pivotal roles in the regulation of energy homeostasis, and its activation could improve glucose uptake, promote mitochondrial biogenesis and increase glycolysis. Recent research has even suggested that AMPK activation contributed to endurance enhancement without exercise. Here we report that the natural product arctigenin from the traditional herb Arctium lappa L. (Compositae) strongly increased AMPK phosphorylation and subsequently up-regulated its downstream pathway in both H9C2 and C2C12 cells. It was discovered that arctigenin phosphorylated AMPK via calmodulin-dependent protein kinase kinase (CaMKK) and serine/threonine kinase 11(LKB1)-dependent pathways. Mice treadmill based in vivo assay further indicated that administration of arctigenin improved efficiently mice endurance as reflected by the increased fatigue time and distance, and potently enhanced mitochondrial biogenesis and fatty acid oxidation (FAO) related genes expression in muscle tissues. Our results thus suggested that arctigenin might be used as a potential lead compound for the discovery of the agents with mimic exercise training effects to treat metabolic diseases.
DOI: 10.1111/j.1432-1033.1989.tb15185.x
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