The search for functional natural compounds that can improve age-related cognitive decline has recently emerged as an important research focus to promote healthy aging. Now, a study led by researchers at the University of Tsukuba investigated the effects of Trigonelline (TG), a plant alkaloid found in coffee, as well as in fenugreek seed and radish, 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.

The findings are published in GeroScience in an article titled, “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.”

“In recent years, exploring natural compounds with functional properties to ameliorate aging-associated cognitive decline has become a research priority to ensure healthy aging,” wrote the researchers. “In the present study, we investigated the effects of Trigonelline (TG), a plant alkaloid, on memory and spatial learning in 16-week-old senescence-accelerated mouse model SAMP8 using an integrated approach for cognitive and molecular biology aspects.”

After oral administration of TG 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 TG.

The researchers performed a whole-genome transcriptomic analysis of the hippocampus to explore the underlying molecular mechanisms. They observed that signaling pathways related to nervous system development, mitochondrial function, ATP synthesis, inflammation, autophagy, and neurotransmitter release were significantly modulated in the TG group.

“After 30 days of oral administration of TG at the dose of 5 mg/kg/day, the mice were trained in Morris water maze task,” wrote the researchers. “TG-treated SAMP8 mice exhibited significant improvement in the parameters of escape latency, distance moved, and annulus crossing index. Next, we performed a whole-genome transcriptome profiling of the mouse hippocampus using microarrays. Gene ontology analyses showed that a wide range of biological processes, including nervous system development, mitochondrial function, ATP synthesis, and several signaling pathways related to inflammation, autophagy, and neurotransmitter release, were significantly enriched in TG-treated SAMP8 compared to nontreated.”

The research team found that TG suppressed neuroinflammation by negatively regulating the signaling factor Traf6-mediated activation of the transcription factor NF-κB. The findings suggest the efficacy of TG in preventing and improving age-related spatial learning memory impairment.

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