title: trans-Resveratrol in Gnetum gnemon protects against oxidative-stress-induced endothelial senescence.
abstract: Gnetum gnemon is an arboreal dioecious plant that is cultivated in Indonesia. The seeds of this species mainly contain dimeric stilbenoid compounds [gnetin C (1), gnemonoside A (2), and gnemonoside D (3)] along with trans-resveratrol (4). trans-Resveratrol has been reported to have antiaging, anticancer, and antidiabetic effects, as well as being a calorie restriction mimetic. SIRT1 exerts a protective effect against vascular senescence. In this study, the effects of these four main stilbenoid derivatives of a G. gnemon seed endosperm ethanolic extract on endothelial senescence were investigated. In streptozotocin-induced diabetic mice, administration of the G. gnemon ethanolic extract increased SIRT1 and decreased endothelial senescence. The concentration of 1 in blood plasma was 6-fold higher than 4 in these mice. Next, the in vitro effects of the four main stilbenoid derivatives of G. gnemon seeds were investigated. Senescent human umbilical vein endothelial cells were induced by hydrogen peroxide. Endothelial senescence was inhibited by 4, which increased the expression of endothelial nitric oxide synthase and SIRT1, whereas 1-3 had no effect. These results indicated that the ethanolic extract of G. gnemon seeds inhibits endothelial senescence, suggesting that 4 plays a critical role in the prevention of endothelial senescence.
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Ota
authors.forename: Masahiro
authors.initials: M
authors.lastname: Akishita
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tani
authors.forename: Tomoki
authors.initials: T
authors.lastname: Tatefuji
authors.forename: Sumito
authors.initials: S
authors.lastname: Ogawa
authors.forename: Katsuya
authors.initials: K
authors.lastname: Iijima
authors.forename: Masato
authors.initials: M
authors.lastname: Eto
authors.forename: Takuji
authors.initials: T
authors.lastname: Shirasawa
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Ouchi
mesh_terms: D000328:Adult; D000818:Animals; D001572:Benzofurans / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification*; D016922:Cellular Senescence / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental; D035684:Gnetum / Q000737:chemistry*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007214:Indonesia; D051379:Mice; D015394:Molecular Structure; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D000077185:Resveratrol; D012639:Seeds / Q000378:metabolism; D056564:Sirtuin 1 / Q000187:drug effects; D013237:Stereoisomerism; D013267:Stilbenes / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D001572:Benzofurans; D013267:Stilbenes; C584041:gnemonoside A; C584042:gnemonoside D; C575740:gnetin C; D006861:Hydrogen Peroxide; D052250:Nitric Oxide Synthase Type III; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol