Nodakenin, a coumarin compound, ameliorates scopolamine-induced memory disruption in mice Dong Hyun Kim a , Do Yoon Kim b , Young Choong Kim b , Ji Wook Jung c , Seungjoo Lee a , Byung Hoon Yoon a , Jae Hoon Cheong d , Yeong Shik Kim b , Sam Sik Kang b , Kwang Ho Ko b , Jong Hoon Ryu a, ⁎ a 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 b College of Pharmacy, Seoul National University, Kwanak-Gu, Seoul 151-742, Republic of Korea c Department of Herbal Medicinal Resource, College of Health and Welfare, Daegu Haany University, Gyeongsan 712-715, Republic of Korea d Department of Pharmacy, Sahmyook University, Nowon-goo, Seoul 139-742, Republic of Korea Received 19 August 2006; accepted 19 February 2007 Abstract 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 μM). 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. © 2007 Elsevier Inc. All rights reserved. Keywords: Nodakenin; Memory; Passive avoidance test; Y-maze test; Morris water maze; Acetylcholinesterase Introduction Cholinergic neurons in the central nervous system (CNS) are degenerated in patients with Alzheimer's disease, and senile dementia severity and degree of degeneration are correlated with functional loss in this and similar disorders (Davies and Maloney, 1976; Perry et al., 1978). Based on a cholinergic hypothesis, many attempts have been made to reverse cognitive deficits by increasing brain cholinergic activity via acetylcho- linesterase (AChE) inhibitors, acetylcholine precursors, or cholinergic agonists. The cholinergic receptor agonists (mus- carinic and nicotinic) and enhancers of the endogenous levels of acetylcholine (synthesis promoters and inhibitors of its metabolizing enzymes) have been examined as potential treatments for senile dementia of the Alzheimer's type. Among the various approaches attempted, AChE inhibition was the most successful (Giacobini, 1996), and a selective AChE inhibitor, donepezil, has been used to treat mild Alzheimer's disease (Doody, 1999). Angelica gigas Nakai (Umbelliferae) roots have been used traditionally in Korean herbal medicine, where they are called ‘Zam Dang Gui’, to treat anemia, or as a sedative, anodyne, or tonic (Han, 1992). It has also been reported recently that some coumarin compounds and/or extract of A. gigas exhibit anti- amnesic (Yan et al., 2004), anti-tumor (Lee et al., 2003a), Life Sciences 80 (2007) 1944 – 1950 www.elsevier.com/locate/lifescie ⁎ Corresponding author. Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, #1 Hoeki-dong, Dongdeamoon- ku, Republic of Korea 130–701, Korea. Tel.: +82 2 961 9230; fax: +82 2 966 3885. E-mail address: jhryu63@khu.ac.kr (J.H. Ryu). 0024-3205/$ - see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.lfs.2007.02.023