title: Spinosin, a C-glycoside flavonoid, enhances cognitive performance and adult hippocampal neurogenesis in mice.
abstract: Adult neurogenesis has received much attention due to its potential role in neurological or psychiatric disorders such as Alzheimer's disease. In the present study, we examined whether spinosin, a C-glycoside flavonoid from the seeds of Zizyphus jujuba var. spinosa, affects cognitive performance and adult hippocampal neurogenesis in normal naïve mice. The subchronic administration of spinosin (5mg/kg) for 14days significantly increased the latency time in the passive avoidance task. Doublecortin and 5-bromo-2-deoxyuridine immunostaining revealed that the subchronic administration of spinosin (5mg/kg) significantly increased the proliferation and survival of neuronal cells and the number of immature neurons in the hippocampal dentate gyrus region. In addition, we observed an increase in the percentage of BrdU-incorporated cells co-localized with NeuN, a mature neuronal marker, which indicated that spinosin stimulates the differentiation of newly generated cells into mature neurons. Also, the subchronic treatment with spinosin (5mg/kg) increased the expression levels of phosphorylated extracellular-regulated kinase (ERK), phosphorylated cAMP response element-binding protein (CREB) and mature brain-derived neurotrophic factor (mBDNF) in the hippocampus. These findings demonstrate that spinosin has the potential for therapeutic use in treating the cognitive dysfunction observed in neurological or psychiatric disorders by up-regulating adult hippocampal neurogenesis or activating of the ERK-CREB-BDNF signaling pathway.
authors.affiliation: Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul 130-701, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Younghwan
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul 130-701, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Jeon
authors.affiliation: Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul 130-701, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Hyung Eun
authors.initials: HE
authors.lastname: Lee
authors.affiliation: Daehwa Pharmaceutical Co., Ltd., Seongnam 463-400, Gyeonggi-do, Republic of Korea.
authors.forename: In Ho
authors.initials: IH
authors.lastname: Jung
authors.affiliation: Daehwa Pharmaceutical Co., Ltd., Seongnam 463-400, Gyeonggi-do, Republic of Korea.
authors.forename: Yeong-Woo
authors.initials: YW
authors.lastname: Jo
authors.affiliation: Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul 130-701, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Sunhee
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, Sahmyook University, Nowon-goo, Seoul 139-742, Republic of Korea.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Cheong
authors.affiliation: Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul 130-701, Republic of Korea; Department of Pharmaceutical Science, Kyung Hee University, Seoul 130-701, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Dae Sik
authors.initials: DS
authors.lastname: Jang
authors.affiliation: Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul 130-701, Republic of Korea; Department of Oriental Pharmaceutical Science, Kyung Hee University, Seoul 130-701, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea. Electronic address: jhryu63@khu.ac.kr.
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Ryu
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D018891:Dentate Gyrus / Q000166:cytology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects*; D008297:Male; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D005419:Flavonoids; C055669:spinosin; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Adult neurogenesis; Hippocampus; Spinosin; Zizyphus jujuba var. spinosa