The Effect of Alkaloid Extracted from Huperzia Phlegmaria on Cognitive Deficits Scopolamine-Induced in Mice

Abstract

Background: Huperzia phlegmaria has been used for the treatment of neurological disorder. Alkaloids are main bioactive compounds found in Huperzia phlegmaria. We aimed to investigate the acetylcholinesterase (AChE) inhibitory activity in vitro of Huperzia phlegmaria alkaloid extract (HpAE) and protective effects on mice which were induced cognitive deficits by scopolamine. Methods: AChE inhibitory activity and kinetic inhibition mechanism was investigated by Ellman's assay. Mice were administrated orally HpAE (30 mg/kg and 60 mg/kg) for fourteen days, and injected scopolamine at a dose of 1 mg/kg intraperitoneally for four days to induce cognitive impairment. The Y-maze and the Morris water maze were used for evaluating the memory behaviors. Acetylcholine (ACh) levels and AChE activity were measured in brain tissue. Glutathione peroxidase (GPx), superoxide dismutase (SOD) activities, and malondialdehyde (MDA) groups were also evaluated in the mouse brain tissues. Results: Our data showed that HpAE had a strong AChE inhibitory activity with an IC50 value of 5.12 ± 0.48 μg/mL in a concentration-dependent manner. Kinetic inhibition analysis demonstrated that HpAE inhibited AChE followed the mixed inhibition type with Ki (representing the affinity of the enzyme and inhibitor) was 4.37 ± 0.35 μg/mL. Scopolamine induced the cognitive impairment in the Morris Water Maze and Y-maze test along with reduced brain levels of ACh and antioxidant enzyme and increased AChE activity in mouse brain tissues. Treatment with HpAE at both doses (30 mg/kg and 60 mg/kg) decreased the SCP-induced cognitive impairment in both behavioral tests along with decreased acetylcholinesterase activity and MDA level, and increased ACh level and antioxidant enzyme in mouse brain tissues. Conclusion: Our results suggested that the HpAE at both dose (30 mg/kg and 60 mg/kg) may be used for prevent and treatment of Alzheimer’s disease.