title: The antioxidant effect of carnosol in bovine aortic endothelial cells is mainly mediated via estrogen receptor α pathway.
abstract: Antioxidant action is critical for maintaining the normal cardiovascular function and vascular endothelial cell is an important target of estrogen action through estrogen receptor (ER) pathway. This study is carried out to explore the antioxidant effect of carnosol in bovine aortic endothelial cells (BAECs) via ER pathway. The ER subtype specific estrogenic effect of carnosol was further demonstrated by luciferase reporter gene assay in human embryonic kidney (HEK) 293 cells. Carnosol was extracted from Chinese medicine Rosmarinus officinalis. ER positive BAECs were employed in cell proliferation assay and cell apoptosis tests. Oxidative stress by intracellular reactive oxygen species (ROS) were measured via 2'7'-dichlorofluorescein (DCF) production. ERα and ERβ specific antagonists 1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole (MPP) and 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-yl]phenol (PHTPP) were employed as tools in the experiment. ER negative HEK 293 cells were employed in luciferase reporter gene assay. The results indicate that carnosol can effectively attenuate H(2)O(2) induced slowing down of cell growth and increasing of cell apoptosis. At the meantime, carnosol pretreating can also effectively reduce the H(2)O(2) induced intracellular ROS elevation in BAECs. ERα and ERβ antagonist, especially ERα antagonist, can effectively decrease the above antioxidant effects of carnosol. The reporter gene analysis further demonstrates that the action of carnosol on inducing ERE dependent luciferase expression is realized via ER pathway. The conclusion is that carnosol can exert antioxidant effects towards oxidative stress induced by H(2)O(2) in BAECs. And such effects are realized via ER, especially ERα pathway. The results contribute to explain the mechanism of cardiovascular protective function of carnosol in postmenopausal women.
authors.affiliation: Bio-Organic and Natural Products Research Laboratory, Mclean Hospital Harvard Medical School, Belmont, MA 02478, USA.
authors.forename: Pi-wen
authors.initials: PW
authors.lastname: Zhao
authors.forename: David Yue-wei
authors.initials: DY
authors.lastname: Lee
authors.forename: Zhong-ze
authors.initials: ZZ
authors.lastname: Ma
authors.forename: Lian-sha
authors.initials: LS
authors.lastname: Huang
authors.forename: Li-ping
authors.initials: LP
authors.lastname: Sun
authors.forename: Ya-dong
authors.initials: YD
authors.lastname: Li
authors.forename: Jia-xu
authors.initials: JX
authors.lastname: Chen
authors.forename: Jian-zhao
authors.initials: JZ
authors.lastname: Niu
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D045784:Abietanes; D000975:Antioxidants; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D016877:Oxidants; D017382:Reactive Oxygen Species; C068623:carnosol; D004958:Estradiol; D006861:Hydrogen Peroxide