Sesamol Attenuates Scopolamine-Induced Cholinergic Disorders, Neuroinflammation, and Cognitive Deficits in Mice

Alzheimer's disease (AD) is a neurodegenerative disease, characterized by memory loss and cognitive deficits accompanied by neuronal damage and cholinergic disorders. Sesamol, a lignan component in sesame oil, has been proven to have neuroprotective effects. This research aimed to investigate the preventive effects of sesamol on scopolamine (SCOP)-induced cholinergic disorders in C57BL/6 mice. The mice were pretreated with sesamol (100 mg/kg/d, p.o.) for 30 days. Behavioral tests indicated that sesamol supplement prevented SCOP-induced cognitive deficits. Sesamol enhanced the expression of neurotrophic factors and postsynaptic density (PSD) in SCOP-treated mice, reversing neuronal damage and synaptic dysfunction. Importantly, sesamol could balance the cholinergic system by suppressing the AChE activity and increasing the ChAT activity and M1 mAChR expression. Sesamol treatment also inhibited the expression of inflammatory factors and overactivation of microglia in SCOP-treated mice. Meanwhile, sesamol improved the antioxidant enzyme activity and suppressed oxidative stress in SCOP-treated mice and ameliorated the oxidized cellular status and mitochondrial dysfunction in SCOP-treated SH-SY5Y cells. In conclusion, these results indicated that sesamol attenuated SCOP-induced cognitive dysfunction via balancing the cholinergic system and reducing neuroinflammation and oxidative stress.