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

Eur J Pharmacol. 2019 Jan 5;842:270-280. doi: 10.1016/j.ejphar.2018.09.036. Epub 2018 Oct 1.

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 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 (-)-α-bisabolol (100 and 200 mg/kg) significantly reduced the infarcted area and neurological deficits caused by pMCAO. (-)-α-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. (-)-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 (200 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.

Keywords: Brain ischemia; Inflammation; Memory; Neuroprotective effect; α-bisabolol.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Death / drug effects
  • Infarction, Middle Cerebral Artery / complications*
  • Infarction, Middle Cerebral Artery / pathology*
  • Inflammation / metabolism
  • Male
  • Maze Learning / drug effects
  • Memory Disorders / complications
  • Memory Disorders / drug therapy*
  • Memory Disorders / metabolism*
  • Memory Disorders / pathology
  • Mice
  • Monocyclic Sesquiterpenes
  • Neurons / drug effects*
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Sesquiterpenes / pharmacology*
  • Sesquiterpenes / therapeutic use

Substances

  • Biomarkers
  • Monocyclic Sesquiterpenes
  • Neuroprotective Agents
  • Sesquiterpenes
  • bisabolol