title: Reactive oxygen species-induced impairment of endothelium-dependent relaxations in rat aortic rings: protection by methanolic extracts of Phoebe grandis.
abstract: Generation of reactive oxygen species plays a pivotal role in the development of cardiovascular diseases. The present study describes the effects of the methanolic extract of Phoebe grandis (MPG) stem bark on reactive oxygen species-induced endothelial dysfunction in vitro. Endothelium-dependent (acetylcholine, ACh) and -independent relaxation (sodium nitroprusside, SNP) was investigated from isolated rat aorta of Sprague-Dawley (SD) in the presence of the β-NADH (enzymatic superoxide inducer) and MPG extract. Superoxide anion production in aortic vessels was measured by lucigen chemiluminesence. Thirty minutes incubation of the rat aorta in vitro with β-NADH increased superoxide radical production and significantly inhibited ACh-induced relaxations. Pretreatment with MPG (0.5, 5 and 50 μg/mL) restored the ACh-induced relaxations (R(max): 92.29% ± 2.93, 91.02% ± 4.54 and 88.31 ± 2.36, respectively) in the presence of β-NADH. MPG was ineffective in reversing the impaired ACh-induced relaxations caused by pyrogallol, a non-enzymatic superoxide generator. Superoxide dismutase (a superoxide scavenger), however, reversed the impaired ACh relaxations induced by both β-NADH and pyrogallol. MPG also markedly inhibited the β-NADH-induced generation of the superoxide radicals. Furthermore, MPG scavenging peroxyl radicals generated by tBuOOH (10⁻⁴ M).These results indicate that MPG may improve the endothelium dependent relaxations to ACh through its scavenging activity as well as by inhibiting the NADH/NADPH oxidase induced generation of superoxide anions.
authors.affiliation: Centre of Natural Products and Drug Discovery (CENAR), Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Lau
authors.initials: L
authors.lastname: Yeh-Siang
authors.forename: Gopal
authors.initials: G
authors.lastname: Subramaniam
authors.forename: A Hamid A
authors.initials: AH
authors.lastname: Hadi
authors.forename: Dharmani
authors.initials: D
authors.lastname: Murugan
authors.forename: Mohd Rais
authors.initials: MR
authors.lastname: Mustafa
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D019770:Lauraceae / Q000737:chemistry*; D000432:Methanol / Q000737:chemistry; D009126:Muscle Relaxation / Q000187:drug effects; D009249:NADP / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D010936:Plant Extracts; D017382:Reactive Oxygen Species; D009249:NADP; D000432:Methanol