ABSTRACT
The pathophysiology of ischemic stroke involves multiple events such as inflammation and oxidative stress which will lead to neuronal death and cognitive deficits. The (-)-α-bisabolol is a monocyclic sesquiterpene alcohol found in various plants and mainly in Matricaria chamomilla, which exerts antioxidant, anti-inflammatory, and anti-apoptotic activities. The aim of this work was to investigate the neuroprotective effects of (-)-α-bisabolol in mice underwent permanent occlusion of the middle cerebral artery (pMCAO). Animals were treated with (-)-α-bisabolol (50, 100 and 200â¯mg/kg/day, orally) or vehicle (3% tween 80) one day before and 1â¯h after pMCAO and the treatment continued once daily for the following five days. The treatment with (-)-α-bisabolol (100 and 200â¯mg/kg) significantly reduced the infarcted area and neurological deficits caused by pMCAO. (-)-α-bisabolol at the 200â¯mg/kg dose increased cell viability and decreased neuronal degeneration, as evaluated by cresyl violet and Fluoro-Jade C stainings, respectively. (-)-α-bisabolol also increased the locomotor activity which was reduced by cerebral ischemia and improved pMCAO-induced working, spatial, object recognition, and aversive memories deficits. (-)-α-bisabolol (200â¯mg/kg) significantly prevented the increase of myeloperoxidase (MPO) activity, TNF-α immunoreactivity in the temporal cortex, and the increase of iNOS both in the temporal cortex and in the striatum. (-)-α-bisabolol treatment also prevented astrogliosis in these areas. These data showed that (-)-α-bisabolol provides neuroprotective action probably due to its anti-inflammatory activity, although other mechanisms cannot be discarded.
Subject(s)
Infarction, Middle Cerebral Artery/complications , Infarction, Middle Cerebral Artery/pathology , Memory Disorders/drug therapy , Memory Disorders/metabolism , Neurons/drug effects , Neuroprotective Agents/pharmacology , Sesquiterpenes/pharmacology , Animals , Biomarkers/metabolism , Cell Death/drug effects , Inflammation/metabolism , Male , Maze Learning/drug effects , Memory Disorders/complications , Memory Disorders/pathology , Mice , Monocyclic Sesquiterpenes , Neurons/pathology , Neuroprotective Agents/therapeutic use , Sesquiterpenes/therapeutic useABSTRACT
BACKGROUND: Cerebral ischemia is a common disease and one of the most common causes of death and disability worldwide. The lack of glucose and oxygen in neuronal tissue leads to a series of inflammatory events, culminating in neuronal death. Eriodictyol is a flavonoid isolated from the Chinese herb Dracocephalum rupestre that has been proven to have anti-inflammatory properties. HYPOTHESIS/PURPOSE: Thus, the present study was designed to explore whether eriodictyol has neuroprotective effects against the neuronal damage, motor and memory deficits induced by permanent middle cerebral artery occlusion (pMCAO) in mice. STUDY DESIGN: Animals were orally treated with eriodictyol (1, 2 and 4mg/kg) or vehicle (saline) 30min before pMCAO, 2h after, and then once daily for the following five days. METHODS: The parameters studied were neuronal viability, brain infarcted area; sensorimotor deficits; exploratory activity; working and aversive memory; myeloperoxidase (MPO) activity; TNFα, iNOS and GFAP immunoreactivity. RESULTS: The treatment with eriodictyol prevented neuronal death, reduced infarct area and improved neurological and memory deficits induced by brain ischemia. The increase of MPO activity and TNF-α, iNOS and GFAP expression were also reduced by eriodictyol treatment. CONCLUSION: These findings demonstrate that eriodictyol exhibit promising neuroprotection effects against the permanent focal ischemia cerebral injury in the mice experimental model and the underlying mechanisms might be mediated through inhibition of neuroinflammation.