Abstract

Objectives : Alzheimer's disease(AD) is a progressive and fatal neurodegenerative disease characterized by amyloid plaques and neurofibrillary tangles. These plaques are associated with degenerating neuronal processes and consist primarily of fibrillary aggregates of β-amyloid protein, generated from amyloid precursor protein (APP). Another amyloidogenic fragment, the carboxyl terminus (CT) of APP, which is composed of 99-105 amino acid residues containing the complete Aβ sequence, also appears to be toxic to neurones. Recent evidence suggests that CT105, carboxy terminal 105 amino acids peptide fragment of APP, may be an important factor causing neurotoxicity in AD. Methods : Although a variety of oriental prescriptions including Pinelliae rhizoma has been traditionally utilized for the treatment of AD, their pharmacological effects and action mechanisms have not yet fully elucidated. In the present study, we investigated effects of the dichloromethane extract of Pinelliae rhizoma(PINR) on neurotoxicity and the formation of reactive oxygen species(ROS) and nitric oxide(NO) in SK-N-SH cells overexpressed with CT105. In addition, we evaluated its radical scavenging activity and effects on acetylcholinesterase(AChE) activity. Furthermore, effects on cognitive deficits induced by scopolamine treatment were also evaluated in rats. Results : We found in this study that PINR significantly inhibited apoptotic neuronal death induced by CT105 overexpression in SK-N-SH cells. Based on morphological examinations by phase-contrast microscopy, PINR reversed apoptotic changes of CT105-expressed cells. It was also found that PINR significantly promoted neurite outgrowth and inhibited formation of ROS and NO. PINR was shown to scavenge DPPH radicals and noncompetitively inhibit AChE activity. Furthermore, it reduced scopolamine-induced memory impairment in rats, assessed by passive avoidance test. Conclusions : Taken together, these results demonstrate that PINR exhibits neuroprotective, antioxidant, and memory enhancing effects, and therefore, it may be beneficial for the treatment of AD.