title: Arctigenin reduces neuronal responses in the somatosensory cortex via the inhibition of non-NMDA glutamate receptors.
abstract: Lignans are biologically active phenolic compounds related to lignin, produced in different plants. Arctigenin, a dibenzylbutyrolactone-type lignan, has been used as a neuroprotective agent for the treatment of encephalitis. Previous studies of cultured rat cerebral cortical neurones raised the possibility that arctigenin inhibits kainate-induced excitotoxicity. The aims of the present study were: 1) to analyse the effect of arctigenin on normal synaptic activity in ex vivo brain slices, 2) to determine its receptor binding properties and test the effect of arctigenin on AMPA/kainate receptor activation and 3) to establish its effects on neuronal activity in vivo. Arctigenin inhibited glutamatergic transmission and reduced the evoked field responses. The inhibitory effect of arctigenin on the evoked field responses proved to be substantially dose dependent. Our results indicate that arctigenin exerts its effects under physiological conditions and not only on hyper-excited neurons. Furthermore, arctigenin can cross the blood-brain barrier and in the brain it interacts with kainate sensitive ionotropic glutamate receptors. These results indicate that arctigenin is a potentially useful new pharmacological tool for the inhibition of glutamate-evoked responses in the central nervous system in vivo.
authors.affiliation: Department of Physiology and Neurobiology, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Sándor
authors.initials: S
authors.lastname: Borbély
authors.affiliation: Department of Physiology and Neurobiology, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Gergely
authors.initials: G
authors.lastname: Jócsák
authors.affiliation: Department of Physiology and Neurobiology, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Kinga
authors.initials: K
authors.lastname: Moldován
authors.affiliation: Department of Plant Anatomy, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Éva
authors.initials: É
authors.lastname: Sedlák
authors.affiliation: Department of Plant Anatomy, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Éva
authors.initials: É
authors.lastname: Preininger
authors.affiliation: Department of Plant Anatomy, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Imre
authors.initials: I
authors.lastname: Boldizsár
authors.affiliation: Department of Physiology and Neurobiology, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Tóth
authors.affiliation: Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK.
authors.forename: Palmi T
authors.initials: PT
authors.lastname: Atlason
authors.affiliation: Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK.
authors.forename: Elek
authors.initials: E
authors.lastname: Molnár
authors.affiliation: Department of Physiology and Neurobiology, Eötvös Loránd University, Budapest, Hungary. Electronic address: vilagildi@ttk.elte.hu.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Világi
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005663:Furans / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000502:physiology*; D013003:Somatosensory Cortex / Q000187:drug effects / Q000502:physiology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D005663:Furans; D017705:Lignans; D017470:Receptors, Glutamate; C071942:arctigenin
keywords: Arctigenin; Brain slices; Evoked field potentials; In vivo experiments; Ionotropic glutamate receptors; Rat