Schisandra Extract and Ascorbic Acid Synergistically Enhance Cognition in Mice Through Modulation of Mitochondrial Respiration

Nutrients. 2020 Mar 25;12(4):897. doi: 10.3390/nu12040897.


Cognitive decline is observed in aging and neurodegenerative diseases, including Alzheimer's disease (AD) and dementia. Intracellular energy produced via mitochondrial respiration is used in the regulation of synaptic plasticity and structure, including dendritic spine length and density, as well as for the release of neurotrophic factors involved in learning and memory. To date, a few synthetic agents for improving mitochondrial function have been developed for overcoming cognitive impairment. However, no natural compounds that modulate synaptic plasticity by directly targeting mitochondria have been developed. Here, we demonstrate that a mixture of Schisandra chinensis extract (SCE) and ascorbic acid (AA) improved cognitive function and induced synaptic plasticity-regulating proteins by enhancing mitochondrial respiration. Treatment of embryonic mouse hippocampal mHippoE-14 cells with a 4:1 mixture of SCE and AA increased basal oxygen consumption rate. We found that mice injected with the SCE-AA mixture showed enhanced learning and memory and recognition ability. We further observed that injection of the SCE-AA mixture in mice significantly increased expression of postsynaptic density protein 95 (PSD95), an increase that was correlated with enhanced brain-derived neurotrophic factor (BDNF) expression. These results demonstrate that a mixture of SCE and AA improves mitochondrial function and memory, suggesting that this natural compound mixture could be used to alleviate AD and aging-associated memory decline.

Keywords: ascorbic acid; hippocampus; mitochondria; schisandra extract; synaptic plasticity.

MeSH terms

  • Animals
  • Ascorbic Acid / pharmacology*
  • Cell Line
  • Cell Respiration / drug effects*
  • Cognition / drug effects*
  • Drug Synergism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Learning / drug effects
  • Male
  • Memory / drug effects
  • Mice
  • Mitochondria / drug effects*
  • Mitochondria / metabolism*
  • Oxygen Consumption / drug effects
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism
  • Schisandra / chemistry*


  • Plant Extracts
  • Ascorbic Acid