title: Curcumol from Rhizoma Curcumae suppresses epileptic seizure by facilitation of GABA(A) receptors.
abstract: Rhizoma Curcumae is a common Chinese dietary spice used in South Asia and China for thousands of years. As the main extract, Rhizoma Curcumae oil has attracted a great interest due to its newly raised therapeutic activities including its pharmacological effects upon central nervous system such as neuroprotection, cognitive enhancement, and anti-seizure efficacy; however the molecular mechanisms and the target identification remain to be established. Here we characterize an inhibitory effect of curcumol, a major bioactive component of Rhizoma Curcumae oil, on the excitability of hippocampal neurons in culture, the basal locomotor activity of freely moving animals, and the chemically induced seizure activity in vivo. Electrophysiological recording showed that acute application of curcumol significantly facilitated the γ-aminobutyric acid (GABA)-activated current in cultured mouse hippocampal neurons and in human embryonic kidney cells expressing α1- or α5-containing A type GABA (GABAA) receptors in a concentration-dependent manner. Measurement of tonic and miniature inhibitory postsynaptic GABAergic currents in hippocampal slices indicated that curcumol enhanced both forms of inhibition. In both pentylenetetrazole and kainate seizure models, curcumol suppressed epileptic activity in mice by prolonging the latency to clonic and tonic seizures and reducing the mortality as well as the susceptibility to seizure, presumably by facilitating the activation of GABAA receptors. Taken together, our results identified curcumol as a novel anti-seizure agent which inhibited neuronal excitability through enhancing GABAergic inhibition.
authors.affiliation: Department of Chinese Materia Medica, College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China; Department of Developmental and Behavioral Pediatrics, Shanghai Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200129, China; Departments of Anatomy and Embryology, Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ding
authors.affiliation: Departments of Anatomy and Embryology, Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Departments of Anatomy and Embryology, Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.affiliation: Departments of Anatomy and Embryology, Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Developmental and Behavioral Pediatrics, Shanghai Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200129, China.
authors.forename: Shining
authors.initials: S
authors.lastname: Deng
authors.affiliation: Departments of Anatomy and Embryology, Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Tian-Le
authors.initials: TL
authors.lastname: Xu
authors.affiliation: Department of Chinese Materia Medica, College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Wei-Hong
authors.initials: WH
authors.lastname: Ge
authors.affiliation: Department of Developmental and Behavioral Pediatrics, Shanghai Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200129, China; Departments of Anatomy and Embryology, Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: wgli@shsmu.edu.cn.
authors.forename: Wei-Guang
authors.initials: WG
authors.lastname: Li
authors.affiliation: Department of Developmental and Behavioral Pediatrics, Shanghai Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200129, China. Electronic address: feili@shsmu.edu.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D030024:Curcuma / Q000737:chemistry*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D005106:Exploratory Behavior / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000378:metabolism*; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D011963:Receptors, GABA-A; D012717:Sesquiterpenes; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C022801:curcumol
keywords: Curcumol; Epilepsy; GABA; GABA(A) receptor