title: (1)H NMR metabolomics to study the effects of diazepam on anisatin induced convulsive seizures.
abstract: The anticonvulsive properties of diazepam have been extensively studied, mainly focusing on the γ-amino butyrate (GABA) system. The aim of this investigation was to integrally analyze the metabolic events related to neuroprotection of diazepam on anisatin-induced convulsive seizures by a NMR-based metabolomic approach combined with histopathological examination and behavior examination. Multivariate analysis on metabolic profiles of the piriform cortex and cerebellum of mice revealed that diazepam could relieve mice suffering from the convulsive seizures by recovering destructed neurotransmitter and neuromodulator metabolism, ameliorating oxidative stress, alleviating the disturbance in energy, amino acid and nucleic acid metabolism in anisatin intoxicated mice. This integrated metabolomics study provided a powerful and highly effective approach to elucidate therapeutic effects and assessed the safety of diazepam. This study should be helpful for our understanding of convulsive seizures, and provide a holistic view of the treatment effects of benzodiazepine on convulsive seizures.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Pei
authors.initials: P
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Wei
authors.affiliation: Center for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, 200 Xiao Ling Wei, Nanjing 210014, PR China. Electronic address: wang.junsong@gmail.com.
authors.forename: Jun-Song
authors.initials: JS
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China. Electronic address: cpu_lykong@126.com.
authors.forename: Ling-Yi
authors.initials: LY
authors.lastname: Kong
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology / Q000627:therapeutic use*; D029523:Illicium; D007783:Lactones / Q000633:toxicity*; D008297:Male; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D008813:Mice, Inbred ICR; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011522:Protons; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D012717:Sesquiterpenes / Q000633:toxicity*; D013141:Spiro Compounds / Q000633:toxicity*
chemical_list: D007783:Lactones; D011522:Protons; D012717:Sesquiterpenes; D013141:Spiro Compounds; D003975:Diazepam; C031244:anisatin
keywords: Anisatin; Convulsive seizures; Diazepam; Metabolomics; NMR