Chauhan_2025_Eur.J.Pharmacol__177558

As people age, Alzheimer's disease, a neurological disorder that develops gradually, affects their memory and cognitive abilities. The two hallmarks of Alzheimer's disease are intracellular buildup of neurofibrillary tangles and extracellular beta-amyloid plaques. In this work, the effects of Perillyl alcohol on experimental sporadic Alzheimer-type dementia produced by intracerebroventricular streptozotocin were investigated. Rats that received streptozotocin infusion experienced cholinergic hypofunction, increased oxidative-nitritive stress, and impaired memory and learning. Between 15 and 27 days following the initial streptozotocin infusion, 13 days of treatment with Perillyl alcohol (25, 50, and 100 mg/kg p.o.) significantly improved learning and memory in Morris water maze and object recognition test paradigms. Perillyl also significantly reduced oxidative-nitritive stress, as seen by a decrease in malondialdehyde and nitrite, and restored reduced glutathione and catalase levels. Acetylcholinesterase activity significantly increased in the current model, indicating cholinergic hypofunction and enhanced neuronal cell damage. Treatment with Perillyl alcohol also significantly decreased the increase in acetylcholinesterase activity, indicating that Perillyl alcohol may be able to prevent neuronal damage and restore cholinergic functions. Perillyl alcohol has been shown to improve spatial memory processing, which may be due to its antioxidant properties and capacity to restore cholinergic functioning. However, more study is required to understand the molecular mechanisms of POH that enhance cognition or prevent neurotoxic damage, which could support its application in neuroprotective effect.