title: Osteogenic activity of diphenyl ether-type cyclic diarylheptanoids derived from Acer nikoense.
abstract: Osteogenic activity of six diarylheptanoids, acerogenin A (1), (R)-acerogenin B (2), aceroside I (3), aceroside B(1) (4), aceroside III (5) and (-)-centrolobol (6) and two phenolic compounds; (+)-rhododendrol (7) and (+)-cathechin (8), isolated from the stem bark of Acer nikoense (Nikko maple) was evaluated using alkaline phosphatase (ALP) activity as a marker for early osteoblast differentiation. We found that the diphenyl ether-type cyclic diarylheptanoids 1-5 promoted ALP activity in mouse preosteoblastic MC3T3-E1 cells without affecting cell proliferation, but linear-type diarylheptanoid 6 and phenolic compounds 7 and 8 did not. Diphenyl ether-type cyclic diarylheptanoids 1-4 also increased protein production of osteocalcin, a late stage maker for osteoblast differentiation, and induced osteoblastic mineralization. Structure-activity relationships of these compounds demonstrated that the stimulative efficacy of aglycones was higher than that of its glycosides. Taken together, diphenyl ether-type cyclic diarylheptanoids promote early- and late-stage osteoblastogenesis, which may open the possibility for the development of novel osteogenic agents.
authors.affiliation: Department of Nutriproteomics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yonezawa
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Akazawa
authors.forename: Masahiko
authors.initials: M
authors.lastname: Inagaki
authors.forename: Byung-Yoon
authors.initials: BY
authors.lastname: Cha
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nagai
authors.forename: Kazumi
authors.initials: K
authors.lastname: Yagasaki
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Akihisa
authors.forename: Je-Tae
authors.initials: JT
authors.lastname: Woo
mesh_terms: D031002:Acer / Q000737:chemistry*; D000469:Alkaline Phosphatase / Q000032:analysis*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D036381:Diarylheptanoids / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D010006:Osteoblasts / Q000187:drug effects*; D010647:Phenyl Ethers / Q000737:chemistry / Q000494:pharmacology; D024301:Plant Bark / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D036381:Diarylheptanoids; D010647:Phenyl Ethers; D010936:Plant Extracts; C031538:phenyl ether; D000469:Alkaline Phosphatase