Nodakenin, a coumarin compound, ameliorates scopolamine-induced memory disruption in mice.
Nodakenin is a coumarin compound initially isolated from the roots of Angelica gigas. In the present study, we investigated the effects of nodakenin on learning and memory impairments induced by scopolamine (1 mg/kg, i.p.) using the passive avoidance test, the Y-maze test, and the Morris water maze test in mice. Nodakenin (10 mg/kg, p.o.) administration significantly reversed scopolamine-induced cognitive impairments in the passive avoidance test and the Y-maze test (P<0.05), and also reduced escape latency during training in the Morris water maze test (P<0.05). Moreover, swimming times and distances within the target zone of the Morris water maze were greater in the nodakenin-treated group than in the scopolamine-treated group (P<0.05). In an in vitro study, nodakenin was found to inhibit acetylcholinesterase activity in a dose-dependent manner (IC(50)=84.7 microM). In addition, nodakenin was also found to inhibit acetylcholinesterase activity for 6 h in an ex-vivo study. These results suggest that nodakenin may be a useful for the treatment of cognitive impairment, and that its beneficial effects are mediated, in part, via the enhancement of cholinergic signaling.
Kim
Dong Hyun
DH
Department of Oriental Pharmaceutical Science and East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.
Kim
Do Yoon
DY
Kim
Young Choong
YC
Jung
Ji Wook
JW
Lee
Seungjoo
S
Yoon
Byung Hoon
BH
Cheong
Jae Hoon
JH
Kim
Yeong Shik
YS
Kang
Sam Sik
SS
Ko
Kwang Ho
KH
Ryu
Jong Hoon
JH
D000704:Analysis of Variance; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003374:Coumarins / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004924:Escape Reaction / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D012601:Scopolamine / Q000633:toxicity*
D002800:Cholinesterase Inhibitors; D003374:Coumarins; D005960:Glucosides; D012601:Scopolamine; C471579:nodakenin