Centre of Natural Products and Drug Discovery (CENAR), Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Molecules. 2011 Apr 6;16(4):2990-3000. doi: 10.3390/molecules16042990.
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.
活性氧的产生在心血管疾病的发展中起着关键作用。本研究描述了麻叶千斤拔茎皮甲醇提取物（MPG）对体外活性氧诱导的内皮功能障碍的影响。在β-NADH（酶超氧化物诱导剂）和 MPG 提取物存在的情况下，研究了来自 Sprague-Dawley（SD）大鼠分离的主动脉的内皮依赖性（乙酰胆碱，ACh）和非依赖性（硝普钠，SNP）松弛。通过 lucigen 化学发光测量主动脉血管中超氧阴离子的产生。β-NADH 体外孵育大鼠主动脉 30 分钟增加超氧自由基的产生，并显著抑制 ACh 诱导的松弛。MPG（0.5、5 和 50μg/mL）预处理恢复了 ACh 诱导的松弛（R（max）：92.29%±2.93、91.02%±4.54 和 88.31±2.36）在β-NADH 存在的情况下。MPG 对邻苯三酚（一种非酶超氧化物生成剂）引起的 ACh 诱导松弛受损没有作用。然而，超氧化物歧化酶（超氧化物清除剂）逆转了由β-NADH 和邻苯三酚引起的受损 ACh 松弛。MPG 还显著抑制了β-NADH 诱导的超氧阴离子的产生。此外，MPG 清除 tBuOOH（10⁻⁴ M）产生的过氧自由基。这些结果表明，MPG 可能通过其清除活性以及抑制 NADH/NADPH 氧化酶诱导的超氧阴离子生成来改善 ACh 依赖的舒张。
