4 research outputs found

    Petasin Activates AMP-Activated Protein Kinase and Modulates Glucose Metabolism

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    Petasin (<b>1</b>), a natural product found in plants of the genus <i>Petasites</i>, has beneficial medicinal effects, such as antimigraine and antiallergy activities. However, whether or not <b>1</b> modulates metabolic diseases is unknown. In this study, the effects of <b>1</b> 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 <i>Petasites japonicus</i> produces an increase in the phosphorylation of AMPK in vitro, and the main active compound <b>1</b> 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 <b>1</b> enhanced glucose tolerance following the administration of a glucose solution to normal mice. The mechanism by which <b>1</b> activates AMPK was subsequently investigated, and an increased intracellular AMP/ATP ratio in the cultured cells treated with <b>1</b> occurred. In addition, treatment with petasin inhibited mitochondrial respiratory chain complex I. Taken together, the present results indicated that <b>1</b> modulates glucose metabolism and activates AMPK through the inhibition of mitochondrial respiration. The preclinical data suggested that petasin (<b>1</b>) could be useful for the treatment of metabolic diseases in humans
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