Ginger improves cognitive function via NGF-induced ERK/CREB activation in the hippocampus of the mouse

J Nutr Biochem. 2014 Oct;25(10):1058-65. doi: 10.1016/j.jnutbio.2014.05.009. Epub 2014 Jun 18.


Ginger (the rhizome of Zingiber officinale Roscoe) has been used worldwide for many centuries in cooking and for treatment of several diseases. The main pharmacological properties of ginger include anti-inflammatory, antihyperglycemic, antiarthritic, antiemetic and neuroprotective actions. Recent studies demonstrated that ginger significantly enhances cognitive function in various cognitive disorders as well as in healthy brain. However, the biochemical mechanisms underlying the ginger-mediated enhancement of cognition have not yet been studied in normal or diseased brain. In the present study, we assessed the memory-enhancing effects of dried ginger extract (GE) in a model of scopolamine-induced memory deficits and in normal animals by performing a novel object recognition test. We found that GE administration significantly improved the ability of mice to recognize novel objects, indicating improvements in learning and memory. Furthermore, to elucidate the mechanisms of GE-mediated cognitive enhancement, we focused on nerve growth factor (NGF)-induced signaling pathways. NGF enzyme-linked immunosorbent assay analysis revealed that GE administration led to elevated NGF levels in both the mouse hippocampus and rat glioma C6 cells. GE administration also resulted in phosphorylation of extracellular-signal-regulated kinase (ERK) and cyclic AMP response element-binding protein (CREB), as revealed by Western blotting analysis. Neutralization of NGF with a specific NGF antibody inhibited GE-triggered activation of ERK and CREB in the hippocampus. Also, GE treatment significantly increased pre- and postsynaptic markers, synaptophysin and PSD-95, which are related to synapse formation in the brain. These data suggest that GE has a synaptogenic effect via NGF-induced ERK/CREB activation, resulting in memory enhancement.

Keywords: ERK/CREB; Ginger; Leaning and memory; NGF; Synaptogenesis; Zingiber officinale.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cognition*
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Disease Models, Animal
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Male
  • Memory / drug effects
  • Mice
  • Mice, Inbred ICR
  • Nerve Growth Factor / genetics
  • Nerve Growth Factor / metabolism*
  • Neurogenesis / drug effects
  • Phosphorylation
  • Plant Extracts / pharmacology*
  • Rats
  • Signal Transduction
  • Zingiber officinale / chemistry*


  • Cyclic AMP Response Element-Binding Protein
  • Plant Extracts
  • Nerve Growth Factor
  • Extracellular Signal-Regulated MAP Kinases