Cognitive-enhancing and antioxidant activities of iridoid glycosides from Scrophularia buergeriana in scopolamine-treated mice.
The cognitive-enhancing activities of E-harpagoside and 8-O-E-p-methoxycinnamoylharpagide (MCA-Hg) isolated from Scrophularia buergeriana were evaluated in scopolamine-induced amnesic mice by the Morris water maze and by passive avoidance tests. E-harpagoside and MCA-Hg significantly improved the impairment of reference memory induced by scopolamine in the Morris water maze test. The mean escape latency, the mean path length and swimming movement were also improved by both compounds. In passive avoidance test, E-harpagoside and MCA-Hg (2 mg/kg body weight, p.o.) significantly ameliorated scopolamine-induced amnesia by as much as 70% of the level found in normal control mice. Donepezil, an acetylcholinesterase inhibitor and the most widely used drug for AD treatment was employed as a positive control. The activity of acetylcholinesterase was inhibited significantly by E-harpagoside or MCA-Hg within the cortex and hippocampus to a level similar to that observed in mice treated with donepezil (2 mg/kg body weight, p.o.). Moreover, treatment with E-harpagoside or MCA-Hg to scopolamine-induced amnesic mice significantly decreased TBARS level which was accompanied by an increase in the activities or contents of glutathione reductase, SOD and reduced GSH. We believe these data demonstrate that E-harpagoside or MCA-Hg exerted potent cognitive-enhancing activity through both anti-acetylcholinesterase and antioxidant mechanisms.
Jeong
Eun Ju
EJ
College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul 151-742, Republic of Korea.
Lee
Ki Yong
KY
Kim
Seung Hyun
SH
Sung
Sang Hyun
SH
Kim
Young Choong
YC
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D003071:Cognition / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006027:Glycosides / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D039823:Iridoids / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D018696:Neuroprotective Agents; D018697:Nootropic Agents / Q000494:pharmacology*; D011714:Pyrans / Q000494:pharmacology; D012601:Scopolamine / Q000494:pharmacology*; D032266:Scrophularia / Q000737:chemistry*; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D006027:Glycosides; D039823:Iridoids; D018727:Muscarinic Antagonists; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D011714:Pyrans; D017392:Thiobarbituric Acid Reactive Substances; C033249:harpagoside; D012601:Scopolamine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D000110:Acetylcholinesterase