title: Identification of Picrasidine C as a Subtype-Selective PPARα Agonist.
abstract: Picrasidine C (1), a dimeric β-carboline-type alkaloid isolated from the root of Picrasma quassioides, was identified to have PPARα agonistic activity by a mammalian one-hybrid assay from a compound library. Among the PPAR subtypes, 1 selectively activated PPARα in a concentration-dependent manner. Remarkably, 1 also promoted PPARα transcriptional activity by a peroxisome proliferator response element-driven luciferase reporter assay. Furthermore, 1 induced the expression of PPARα-regulated genes involved in lipid, glucose, and cholesterol metabolism, such as CPT-1, PPARα, PDK4, and ABCA1, which was abrogated by the PPARα antagonist MK-886, indicating that the effect of 1 was dependent on PPARα activation. This is the first report to demonstrate 1 to be a subtype-selective PPARα agonist with potential application in treating metabolic diseases, such as hyperlipidemia, atherosclerosis, and hypercholesterolemia.
authors.affiliation: College of Life Science, Northeast Forestry University , Harbin 150040, People's Republic of China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Molecular Toxicology, Faculty of Pharmaceutical Sciences, Toho University , Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Kanno
authors.affiliation: Faculty of Pharmaceutical Sciences, Toho University , Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan.
authors.forename: Wei
authors.identifier: http://orcid.org/0000-0003-4143-8597
authors.initials: W
authors.lastname: Li
authors.affiliation: Faculty of Pharmaceutical Sciences, Toho University , Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan.
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University , Shenyang 110016, People's Republic of China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University , Shenyang 110016, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University , Shenyang 110016, People's Republic of China.
authors.forename: Maosheng
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Faculty of Pharmaceutical Sciences, Toho University , Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Koike
authors.affiliation: Department of Molecular Toxicology, Faculty of Pharmaceutical Sciences, Toho University , Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan.
authors.forename: Kiyomitsu
authors.initials: K
authors.lastname: Nemoto
authors.affiliation: College of Life Science, Northeast Forestry University , Harbin 150040, People's Republic of China.
authors.forename: Huicheng
authors.initials: H
authors.lastname: Li
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy; D002243:Carbolines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006937:Hypercholesterolemia / Q000188:drug therapy; D007211:Indoles / Q000494:pharmacology; D050356:Lipid Metabolism; D008055:Lipids; D051379:Mice; D015394:Molecular Structure; D047493:PPAR alpha / Q000819:agonists* / Q000235:genetics; D032270:Picrasma / Q000737:chemistry*; D014157:Transcription Factors / Q000378:metabolism; D002722:Chlorobenzenes
chemical_list: D000470:Alkaloids; D002243:Carbolines; D002784:Cholesterol; D005947:Glucose; D007211:Indoles; D008055:Lipids; D047493:PPAR alpha; D014157:Transcription Factors; C060893:MK-886; D002722:Chlorobenzenes; C010262:norharman