title: Antioxidant and acetylcholinesterase inhibitory activities in vitro of different fraction of Huperzia squarrosa (Forst.) Trevis extract and attenuation of scopolamine-induced cognitive impairment in mice.
abstract: BACKGROUND
  Huperzia squarrosa (Forst.) Trevis is used in traditional medicine for improving memory deficits. Alkaloids, triterpenoids, flavonoids are main bioactive compounds of Huperzia squarrosa (Forst.) Trevis.
  
  
  OBJECTIVE
  This study aimed to investigate the antioxidant, AChE inhibitory activities in vitro of differents fraction of Huperzia squarrosa (Forst.) Trevis extract and neuroprotective effects of EtOAc fraction on scopolamine-induced cognitive impairment in mice.
  
  
  METHODS
  Antioxidant activity was measured by DPPH assay. AChE inhibitory effect in vitro and detail kinetic inhibition mechanism was evaluated by Ellman's assay. For in vivo assay, mice were administrated orally EtOAc fraction (150 and 300mg/kg) for fourteen days, and injected scopolamine at a dose of 1mg/kg intraperitoneally for four days to induce memory injured. The memory behaviors were evaluated using the Morris water maze. ACh levels were measured in brain tissue. Superoxide dismutase (SOD), glutathione peroxidase (GPx) activities, malondialdehyde and protein thiol groups were also evaluated in the brains.
  
  
  RESULTS
  Our data also demonstrated that EtOAc fraction had the strongest antioxidant with an IC50value of 9.35±1.68µg/mL and AChE inhibitory activity with an IC50value of 23.44±3.14μg/mL in a concentration-dependent manner. Kinetic inhibition analysis indicated that EtOAc fraction was mixed inhibition type with Ki (representing the affinity of the enzyme and inhibitor) was 34.75±1.42µg/mL. Scopolamine significantly increased the escape latency time, reduced the crossings number, and swimming time in the target quadrant, while EtOAc fraction reversed these scopolamine-induced effects. EtOAc fraction significantly increased levels of acetylcholine in the brain. EtOAc fraction also significantly decreased oxidative stress in mice.
  
  
  CONCLUSIONS
  Our data suggest that EtOAc fraction of Huperzia squarrosa extract exhibited a strong neuroprotective effect on cognitive impairment, and may be a potential candidate for the treatment of Alzheimer.
authors.affiliation: School of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam. Electronic address: tungasia82@yahoo.es.
authors.forename: Bui Thanh
authors.initials: BT
authors.lastname: Tung
authors.affiliation: School of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam. Electronic address: haipharm@yahoo.com.
authors.forename: Nguyen Thanh
authors.initials: NT
authors.lastname: Hai
authors.affiliation: School of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam. Electronic address: dangkimthu048@gmail.com.
authors.forename: Dang Kim
authors.initials: DK
authors.lastname: Thu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D060825:Cognitive Dysfunction / Q000139:chemically induced / Q000188:drug therapy*; D032501:Huperzia; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D012601:Scopolamine / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D010936:Plant Extracts; D012601:Scopolamine
keywords: Alzheimer; Huperzia squarrosa; Oxidative stress; Scopolamine; Water maze