Petasin Activates AMP-Activated Protein Kinase and Modulates Glucose Metabolism
Petasin Activates AMP-Activated Protein Kinase and Modulates Glucose Metabolism
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DOI：
10.1021/np400867m
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发表时间：
2014-06-01
影响因子：
5.1
通讯作者：
Noguchi, Yasushi
中科院分区：
文献类型：
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作者：
Adachi, Yusuke;Kanbayashi, Yayoi;Noguchi, Yasushi
Petasin（1）是一种存在于蜂斗菜属植物中的天然产物，具有抗偏头痛和抗过敏活性。然而，1是否调节代谢疾病尚不清楚。在这项研究中，1对AMP激活的蛋白激酶（AMPK），这被认为是一个药理学目标，用于治疗代谢性疾病的影响进行了描述。发现蜂斗菜提取物在体外产生AMPK磷酸化的增加，并且分离出主要活性化合物1。当将该化合物口服给药于小鼠时，观察到肝脏、骨骼肌和脂肪组织中AMPK的活化。此外，1预处理增强葡萄糖耐量的葡萄糖溶液给药后，正常小鼠。随后研究了1激活AMPK的机制，并且在用1处理的培养细胞中发生了增加的细胞内AMP/ATP比率。此外，用蜂斗菜肽处理抑制线粒体呼吸链复合物I。综上所述，本研究结果表明，1通过抑制线粒体呼吸调节葡萄糖代谢并激活AMPK。临床前数据表明，蜂斗菜素（1）可用于治疗人类代谢性疾病。
Petasin (1), a natural product found in plants of the genus Petasites, has beneficial medicinal effects, such as antimigraine and antiallergy activities. However, whether or not 1 modulates metabolic diseases is unknown. In this study, the effects of 1 on AMP-activated protein kinase (AMPK), which is considered a pharmacological target for treating metabolic diseases, are described. It was found that an extract of Petasites japonicus produces an increase in the phosphorylation of AMPK in vitro, and the main active compound 1 was isolated. When this compound was administered orally to mice, activation of AMPK in the liver, skeletal muscle, and adipose tissue was observed. Moreover, pretreatment with 1 enhanced glucose tolerance following the administration of a glucose solution to normal mice. The mechanism by which 1 activates AMPK was subsequently investigated, and an increased intracellular AMP/ATP ratio in the cultured cells treated with 1 occurred. In addition, treatment with petasin inhibited mitochondrial respiratory chain complex I. Taken together, the present results indicated that 1 modulates glucose metabolism and activates AMPK through the inhibition of mitochondrial respiration. The preclinical data suggested that petasin (1) could be useful for the treatment of metabolic diseases in humans.