Zhan Chun, Yang Jing
Department of Pharmacology, School of Medicine, Wuhan University, Donghu Road, Wuhan 430071, China.
Pharmacol Res. 2006 Mar;53(3):303-9. doi: 10.1016/j.phrs.2005.12.008. Epub 2006 Feb 3.
Epidemiological studies indicate that the intake of flavonoids is inversely associated with risk of stroke, cardiovascular diseases and cancer. Isoliquiritigenin (ISL), a flavonoid constituent in the root of Glycyrrhiza glabra, is known to have vasorelaxant effect, antioxidant, anti-platelet, anti-tumor, anti-allergic, antiviral activities and estrogenic properties. However, there is no report on the effects of ISL in cerebral ischemia. Evidence demonstrate that the impaired energy metabolism and the excessive generation of reactive oxygen radicals (ROS) contribute to the brain injury associated with cerebral ischemia. In the present study, the protective effects of ISL were investigated in transient middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia-reperfusion injury in rats. Male Sprague-Dawley rats were divided into five groups: sham-operated group, vehicle-pretreated group, and three ISL-pretreated groups (5, 10 and 20 mg kg(-1), i.g.). ISL were administered once a day, for 7 days prior to ischemia. The rats were subjected to 2 h right MCAO via the intraluminal filament technique and 22 h reperfusion. Pretreatment with ISL significantly reduced the cerebral infarct volume and edema and produced significant reduction in neurological deficits. In this study, in order to clarify the mechanism of ISL's protection against cerebral ischemia damage, cerebral energy metabolism, brain Na+K+ATPase activity, malondialdehyde (MDA) content and antioxidant enzyme activities were measured. ISL pretreatment increased the brain ATP content, energy charge (EC) and total adenine nucleotides (TAN) in a dose-dependent manner. The brain Na+K+ATPase activity was protected significantly by pretreatment of ISL for 7 days. Pretreatment with ISL significantly inhibited the increases of brain MDA content and prevented the activities of brain superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) from declines caused by cerebral ischemia-reperfusion. All these findings indicate that ISL has the protective potential against cerebral ischemia injury and its protective effects may be due to the amelioration of cerebral energy metabolism and its antioxidant property.
流行病学研究表明，黄酮类化合物的摄入量与中风、心血管疾病和癌症的风险呈负相关。异甘草素（ISL）是光果甘草根中的一种黄酮类成分，已知具有血管舒张作用、抗氧化、抗血小板、抗肿瘤、抗过敏、抗病毒活性以及雌激素特性。然而，尚无关于ISL对脑缺血影响的报道。有证据表明，能量代谢受损和活性氧自由基（ROS）的过度产生会导致与脑缺血相关的脑损伤。在本研究中，研究了ISL对大鼠短暂性大脑中动脉闭塞（MCAO）诱导的局灶性脑缺血再灌注损伤的保护作用。雄性Sprague-Dawley大鼠分为五组：假手术组、溶剂预处理组和三个ISL预处理组（5、10和20 mg kg(-1)，灌胃）。在缺血前7天，每天给予一次ISL。通过腔内细丝技术对大鼠进行2小时的右侧MCAO和22小时的再灌注。ISL预处理显著降低了脑梗死体积和水肿，并显著减轻了神经功能缺损。在本研究中，为了阐明ISL对脑缺血损伤的保护机制，测定了脑能量代谢、脑Na+K+ATP酶活性、丙二醛（MDA）含量和抗氧化酶活性。ISL预处理以剂量依赖的方式增加了脑ATP含量、能量电荷（EC）和总腺嘌呤核苷酸（TAN）。ISL预处理7天可显著保护脑Na+K+ATP酶活性。ISL预处理显著抑制了脑MDA含量的增加，并防止了脑超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-Px）的活性因脑缺血再灌注而下降。所有这些发现表明，ISL具有抗脑缺血损伤的保护潜力，其保护作用可能归因于脑能量代谢的改善及其抗氧化特性。
