title: An ethanolic extract of Lindera obtusiloba stems causes NO-mediated endothelium-dependent relaxations in rat aortic rings and prevents angiotensin II-induced hypertension and endothelial dysfunction in rats.
abstract: Lindera obtusiloba is a medical herb traditionally used in Asia for the improvement of blood circulation, treatment of inflammation, and prevention of liver damage. The possibility that L. obtusiloba affects vascular reactivity remains to be examined. Therefore, the aim of the present study was to evaluate both the in vitro and in vivo vascular effects of an ethanolic extract of L. obtusiloba stems (LOE). Vascular reactivity was assessed in organ chambers using rat aortic rings and the activation of endothelial NO synthase (eNOS) in cultured bovine aortic endothelial cells. LOE induced endothelium-dependent relaxations, which were abolished by inhibitors of nitric oxide synthase (N (ω)-nitro-L: -arginine) and guanylyl cyclase (1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-L-one), significantly reduced by inhibitors of PI3 kinase (wortmannin and LY294002), and not affected by inhibitors of cyclooxygenase (indomethacin) and endothelium-derived hyperpolarizing factor-mediated responses (charybdotoxin plus apamin). LOE prevented contractile responses to phenylephrine and angiotensin II in rings with endothelium, but not in those without endothelium. LOE caused a concentration-dependent phosphorylation of Akt at Serine473 and eNOS at Serine1177 in endothelial cells. Thereafter, the vasoprotective effect of LOE was investigated in an experimental model of hypertension in rats. Intake of LOE prevented the angiotensin II-induced increase in systolic blood pressure, and endothelial dysfunction to acetylcholine and oxidative stress as assessed using dihydroethidine in aortic rings. The present findings indicate that LOE has vasoprotective and antihypertensive properties most likely by stimulating the endothelial formation of NO and inhibiting oxidative stress.
authors.affiliation: Research and Development Center, Hanwha Pharma Co., Ltd, Chuncheon, Republic of Korea.
authors.forename: Jung-Ok
authors.initials: JO
authors.lastname: Lee
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Oak
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Jung
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Park
authors.forename: Cyril
authors.initials: C
authors.lastname: Auger
authors.forename: Kyoung Rak
authors.initials: KR
authors.lastname: Kim
authors.forename: Seung-Woo
authors.initials: SW
authors.lastname: Lee
authors.forename: Valérie B
authors.initials: VB
authors.lastname: Schini-Kerth
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000737:chemistry; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D027443:Lindera / Q000737:chemistry*; D008297:Male; D008518:Medicine, East Asian Traditional; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D018547:Plant Stems; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D010936:Plant Extracts; D000804:Angiotensin II; D009569:Nitric Oxide; D000431:Ethanol; D052250:Nitric Oxide Synthase Type III