In recent years, exploring natural compounds with functional properties to ameliorate aging-associated cognitive decline has become a research priority to ensure healthy aging. In a new study, researchers at the University of Tsukuba investigated the effects of trigonelline — a naturally occurring alkaloid compound found in various plants, including coffee beans, fenugreek, and Japanese radish — on memory and spatial learning in a mouse model of accelerated aging.
Schematic diagram representing the mechanism of action of trigonelline. Image credit: Aktar et al., doi: 10.1007/s11357-023-00919-x.
Cognitive aging refers to age-related impairments in cognitive functions, including slower problem-solving, reduced fluid reasoning, diminished perceptual speed, and impaired memory and spatial ability.
It stands as one of the most common health concerns among older individuals.
It is estimated that cognitive impairment affects over 11.7% of adults aged 65 and above, with the prevalence increasing to approximately 40% among those aged 80 and older.
According to the WHO, neurodegenerative disorders will rank second among all causes of natural mortality by 2040.
The rise in life expectancy worldwide, particularly in advanced nations, contributes to a substantial increase in the global incidence of cognitive impairment.
Cognitive aging significantly impacts the quality of life for older adults, places strain on healthcare providers and systems and imposes substantial economic burdens on families and society as a whole.
Therefore, it is imperative to take proactive measures to support brain health among older adults and foster healthy aging on a broader scale.
“Trigonelline has been extensively studied for its numerous biological activities, including antimicrobial, anticancer, antidiabetic, antihypertensive, and anti-hyperlipidemic effects,” said University of Tsukuba’s Professor Hiroko Isoda and colleagues.
“Notably, previous studies also reported that trigonelline promotes the regeneration of dendrites and axons in cortical neurons and inhibits the formation of advanced glycation end products in vitro, and improves learning and memory impairment in the in vivo models of Alzheimer’s disease and neuroinflammation.”
“However, the effects of trigonelline on age-related cognitive decline and the underlying molecular mechanisms remain to be fully investigated.”
In their study, the authors investigated the effects of trigonelline on memory and spatial learning from both a cognitive and molecular biology perspective in an integrated manner using a senescence-accelerated mouse prone 8 (SAMP8) model.
Following oral administration of trigonelline to SAMP8 mice for 30 days, the Morris water maze test indicated a significant improvement in spatial learning and memory performance compared with SAMP8 mice that did not receive trigonelline.
Next, the researchers performed whole-genome transcriptomic analysis of the hippocampus to explore the underlying molecular mechanisms.
They found that signaling pathways related to nervous system development, mitochondrial function, ATP synthesis, inflammation, autophagy, and neurotransmitter release were significantly modulated in the trigonelline group.
Furthermore, the scientists found that trigonelline suppressed neuroinflammation by negatively regulating signaling factor Traf6-mediated activation of the transcription factor NF-κB.
Additionally, quantitative protein analysis confirmed that the levels of inflammatory cytokines TNF-α and IL-6 were significantly decreased and the levels of neurotransmitters dopamine, noradrenaline, and serotonin were significantly increased in the hippocampus.
“Our integrated bio-cognitive approach highlights the potential of trigonelline in alleviating age-related memory and spatial impairment,” the authors said.
The research is described in a paper published in the journal GeroScience.
_____
S. Aktar et al. Transcriptomics and biochemical evidence of trigonelline ameliorating learning and memory decline in the senescence-accelerated mouse prone 8 (SAMP8) model by suppressing proinflammatory cytokines and elevating neurotransmitter release. GeroScience, published online September 18, 2023; doi: 10.1007/s11357-023-00919-x
