title: Petasin activates AMP-activated protein kinase and modulates glucose metabolism.
abstract: 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.
authors.affiliation: Frontier Research Laboratories, Institute for Innovation, Ajinomoto Co. Inc. , 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki-shi, 210-8681, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Adachi
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Kanbayashi
authors.forename: Ikue
authors.initials: I
authors.lastname: Harata
authors.forename: Risa
authors.initials: R
authors.lastname: Ubagai
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takimoto
authors.forename: Katsuya
authors.initials: K
authors.lastname: Suzuki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Miwa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Noguchi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D007564:Japan; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D015394:Molecular Structure; D036901:Petasites / Q000737:chemistry; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D012717:Sesquiterpenes; C418727:petasin; D055372:AMP-Activated Protein Kinases; D005947:Glucose