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

Abstract

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.

Neuroprotective Effects of Thymoquinone by the Modulation of ER Stress and Apoptotic Pathway in In Vitro Model of Excitotoxicity

“…Numerous studies have reported that many natural compounds can induce neuronal differentiation, outgrowth, survival, and improved synaptic function in the central nervous system. Jang et al have demonstrated 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 [ 22 ].…”

Hub Genes, Diagnostic Model, and Predicted Drugs Related to Iron Metabolism in Alzheimer's Disease

“…Jang et al . found that a mixture of Schisandra Chinensis extract and ascorbic acid improves mitochondrial function and memory and can also be used to alleviate AD and aging-related memory decline (Jang et al, 2020 ). Dextromethorphan (DB00514) is an NMDA receptor antagonist.…”

Antioxidant Effects of Schisandra chinensis Fruits and Their Active Constituents

“…The S.chisandra lignan gomisin J up-regulated apoptosis signaling and decreased the dissociation of hexokinase II from the voltage-dependent anion channel (VDAC) in mitochondria, thus reducing aerobic glycolysis in glioma cell lines [ 71 ]. Mixture of S. chinensis extract and ascorbic acid restored mitochondrial respiration, improved cognitive function, and induced synaptic plasticity in mice [ 72 ].…”