Behavioural Brain Research 197 (2009) 239–245 Contents lists available at ScienceDirect Behavioural Brain Research journal homepage: www.elsevier.com/locate/bbr Short communication Ginsenosides attenuate kainic acid-induced synaptosomal oxidative stress via stimulation of adenosine A 2A receptors in rat hippocampus Eun-Joo Shin a,1 , Young Ho Koh b,1 , A-Young Kim b , Seung-Yeoul Nah c , Ji Hoon Jeong d , Jong-Seok Chae a , Sun Cheol Kim a , Tran Phi Hoang Yen e , Hyoung-Jong Yoon a , Won-Ki Kim f , Kwang-Ho Ko g , Hyoung-Chun Kim a,∗ a Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, South Korea b Laboratory of Molecular Neurogenetics, ILSONG Institute of Life Science, Hallym University, Anyang, South Korea c Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul, South Korea d Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea e Department of Physical Chemistry, Faculty of Pharmacy, Medicine and Pharmacy University of Hochiminh City, Viet Nam f Department of Neuroscience, School of Medicine, Korea University, South Korea g Department of Pharmacology, College of Pharmacy, Seoul National University, Seoul, South Korea article info Article history: Received 13 June 2008 Received in revised form 20 August 2008 Accepted 22 August 2008 Available online 3 September 2008 Keywords: Ginsenosides Kainate Synaptosome Oxidative stress Hippocampus Adenosine A 2A receptor abstract Treatment with ginsenosides attenuated KA-induced seizures and oxidative stress in the synaptosome, and reduced synaptic vesicles at the presynaptic terminals dose-dependently. The adenosine A 2A receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl) xanthine reversed the ginsenoside-mediated pharmacolog- ical actions. Neither the adenosine A 1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine nor the adenosine A 2B receptor antagonist alloxazine affected the ginsenoside-mediated pharmacological actions. Our results suggest that ginsenosides block KA-induced synaptosomal oxidative stress, associated with hippocampal degeneration, through activation of adenosine A 2A receptors. © 2008 Elsevier B.V. All rights reserved. 1. Introduction Adenosine is an endogenous purine nucleoside that modulates many physiological processes. In particular, it may act as a neu- romodulator in the central nervous system. Cellular signaling by adenosine occurs through four known adenosine receptor subtypes (A 1 ,A 2A ,A 2B ,A 3 ), all of which are G-protein-coupled receptors with seven transmembrane domains [11]. Adenosine has been recog- nized as an endogenous anti-convulsant [8]. Kainate (KA)-induced brain damage has been used as a model for temporal lobe epilepsy and excitotoxic neurodegenerative dis- order [36]. It has been demonstrated that the levels of adenosine A 1 receptors are reduced in temporal lobe epileptic [13] and ∗ Corresponding author at: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Hyoja-2-dong 192-1, Chunchon 200-701, Kangwon-do, South Korea. Tel.: +82 33 250 6917; fax: +82 33 255 7865. E-mail address: kimhc@kangwon.ac.kr (H.-C. Kim). 1 These authors are contributed equally to this study. experimental epileptic brains [9]. Another report suggested that activation of adenosine A 2A receptors protected against KA exci- totoxicity [19]. Similarly, the central activation of adenosine A 2A receptors contributes to seizure suppression in audiogenic brain- stem epilepsy [17]. Furthermore, adenosine release evoked by KA may be involved in the production of free radicals [3]. Accumulat- ing evidence indicates that oxidative stress may contribute to the development of seizures induced by KA [20,34,35]. Ginseng, Panax ginseng C.A. Meyer, is the best known of Asian medicinal plants and has long been used as a folk medicine. Active constituents found in most ginseng species include ginsenosides, polysaccharides, peptides, polyacetylenic alcohols, and fatty acids [2]. The major components responsible for the actions of ginseng are the ginsenosides, also known as ginseng saponins [40]. Previously, Henley et al. showed that in the rat hippocampus, almost all [ 3 H] KA binding sites were found in the synaptoso- mal fraction, with almost no binding to the microsomal fraction where most [ 3 H] AMPA binding was located, suggesting their loca- tion within the synapse [15]. The synaptosomal preparation has particular advantages; it is the simplest preparation that retains 0166-4328/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2008.08.038