(-)-alpha-bisabolol prevents neuronal damage and memory deficits through reduction of proinflammatory markers induced by permanent focal cerebral ischemia in mice

摘要

The pathophysiology of ischemic stroke involves multiple events such as inflammation and oxidative stress which will lead to neuronal death and cognitive deficits. The (-)-alpha-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 (-)-alpha-bisabolol in mice underwent permanent occlusion of the middle cerebral artery (pMCAO). Animals were treated with (-)-alpha-bisabolol (50, 100 and 200 mg/kg/day, orally) or vehicle (3% tween 80) one day before and 1 h after pMCAO and the treatment continued once daily for the following five days. The treatment with (-)-alpha-bisabolol (100 and 200 mg/kg) significantly reduced the infarcted area and neurological deficits caused by pMCAO. (-)-alpha-bisabolol at the 200 mg/kg dose increased cell viability and decreased neuronal degeneration, as evaluated by cresyl violet and Fluoro-Jade C stainings, respectively. (-)-alpha-bisabolol also increased the locomotor activity which was reduced by cerebral ischemia and improved pMCAO-induced working, spatial, object recognition, and aversive memories deficits. (-)-alpha-bisabolol (200 mg/kg) significantly prevented the increase of myeloperoxidase (MPO) activity, TNF-alpha immunoreactivity in the temporal cortex, and the increase of iNOS both in the temporal cortex and in the striatum. (-)-alpha-bisabolol treatment also prevented astrogliosis in these areas. These data showed that (-)-alpha-bisabolol provides neuroprotective action probably due to its anti-inflammatory activity, although other mechanisms cannot be discarded.