Aegle marmelos leaf extract ameliorates the cognitive impairment and oxidative stress induced by intracerebroventricular streptozotocin in male rats

Aims: Aegle marmelos (L.) Correa (A. marmelos) has been used in Ayurvedic medicine as a brain tonic however its neuroprotective effect against streptozotocin (STZ) induced cognitive impairment and oxidative stress has not been reported yet in vivo. Therefore, the present study was attempted to investigate the neuroprotective potential of ethanolic extract of A. marmelos leaves (AME) on STZ induced memory impairment in male rats. Main methods: Albino Wistar rats were pre-treated orally with AME at the doses 200 and 400 mg/kg for two weeks, followed by intracerebroventricular (i.c.v.) injection of STZ (3 mg/kg) on day 1 and 3. Two weeks after STZ administration, behavioural parameters were monitored using Morris water maze task. Biochemical and histopathological studies were carried out after three weeks of STZ administration. The levels of oxidative stress markers (malondialdehyde (MDA), glutathione, nitrite, catalase) neuroinflammatory mediators; tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and acetylcholinesterase (AChE) activity were estimated in hippocampus of rat brain. Donepezil (5 mg/kg) was taken as a standard drug. Key findings: The levels of MDA, nitrite, TNF-alpha and IL-6 were significantly increased while glutathione levels were significantly decreased in hippocampus of STZ-treated rats. Further, a significant decrease in the activity of catalase and increase in AChE activity was observed indicating cholinergic hypofunction and neuronal damage in STZ-treated animals. All these alterations were significantly ameliorated by AME in a dose dependent manner. Significance: The neuroprotective potential of A. marmelos against STZ induced oxidative stress and cognitive deficit in rats indicates its therapeutic value in Alzheimer's disease (AD).