title: Endothelium-dependent vasorelaxant and antiproliferative effects of apigenin.
abstract: This study was designed to determine whether the relaxant effect of apigenin was endothelium dependent and to examine the possible antiproliferative effect of apigenin. Apigenin relaxed the phenylephrine-precontracted endothelium-intact aortic rings with IC(50) value of 3.7+/-0.5 microM and removal of a functional endothelium significantly attenuated this relaxation (IC(50)=8.2+/-0.9 microM). However, apigenin did not affect the 0.1 microM phorbol 12,13-dibutyrate-induced contraction (IC(50)=34.6+/-1.2 microM) within the concentration range that relaxed the phenylephrine-contracted arteries, suggesting that apigenin did not influence protein kinase C-mediated contractile mechanisms in rat aorta. Pretreatment of apigenin significantly potentiated the relaxant effect of acetylcholine on phenylephrine-induced contraction. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME) or methylene blue reduced the relaxant effect of apigenin. Apigenin (10 microM) increased the guanosine 3',5'-cyclic monophosphate (cGMP) content of endothelium-intact tissues. Pretreatment with L-NAME (100 microM) or removal of endothelium significantly suppressed the effect of apigenin on cGMP production. In addition, apigenin significantly inhibited [3H]thymidine incorporation into DNA of primary cultured rat aortic smooth muscle cell in a dose-dependent manner. These findings suggest that besides influx and release of Ca(2+), nitric oxide (NO) and cGMP may account for the apigenin-induced endothelium-dependent relaxation and hypotensive activity. Both vasorelaxant and antiproliferative activities may contribute to a benefit of apigenin in the vascular system.
authors.affiliation: Department of Pharmacology, The School of Basic Medical Science, Peking University, Beijing 100083, China.
authors.forename: Y H
authors.initials: YH
authors.lastname: Zhang
authors.forename: Y S
authors.initials: YS
authors.lastname: Park
authors.forename: T J
authors.initials: TJ
authors.lastname: Kim
authors.forename: L H
authors.initials: LH
authors.lastname: Fang
authors.forename: H Y
authors.initials: HY
authors.lastname: Ahn
authors.forename: J T
authors.initials: JT
authors.lastname: Hong
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
authors.forename: C K
authors.initials: CK
authors.lastname: Lee
authors.forename: Y P
authors.initials: YP
authors.lastname: Yun
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D047310:Apigenin; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology*; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000378:metabolism
chemical_list: D005419:Flavonoids; D015240:Phorbol 12,13-Dibutyrate; D047310:Apigenin; D006152:Cyclic GMP; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester; D013936:Thymidine