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.