Spinosin, a C-glycoside flavonoid, enhances cognitive performance and adult hippocampal neurogenesis in mice

Pharmacol Biochem Behav. 2016 Jun:145:9-16. doi: 10.1016/j.pbb.2016.03.007. Epub 2016 Mar 17.

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.

Keywords: Adult neurogenesis; Hippocampus; Spinosin; Zizyphus jujuba var. spinosa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning / drug effects*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cell Count
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cognition / drug effects*
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Dentate Gyrus / cytology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Flavonoids / pharmacology*
  • Hippocampus / cytology*
  • Hippocampus / drug effects*
  • Male
  • Mice
  • Neural Stem Cells / cytology
  • Neural Stem Cells / drug effects
  • Neurogenesis / drug effects*
  • Phosphorylation / drug effects
  • Signal Transduction / drug effects

Substances

  • Brain-Derived Neurotrophic Factor
  • Cyclic AMP Response Element-Binding Protein
  • Flavonoids
  • spinosin
  • Extracellular Signal-Regulated MAP Kinases