Study: Trigonelline Demonstrates Improvements in Learning, Memory, Suppressing Inflammation

Trigonelline, a plant alkaloid, demonstrated improvements in learning and memory, while suppressing proinflammatory cytokines in a study of mouse models, according to a study published in GeroScience.

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The study authors used 16-week-old senescence-accelerated mouse prone 8 models to determine the effects trigonelline has on memory and spatial learning. They used an integrated approach for cognitive and molecular biology aspects to calculate the findings.

The mice were administered trigonelline orally for 30 days at a dose of 5 mg/kg per day. The study investigators trained the mice in a Morris Water Maze test, which was used to evaluate the memory ability of the hippocampus in the mice.

Between the groups of mice, there were no significant differences in the maze test on the first day. As the training continued, the control group of mice had significant decreases in the time it took them to finish the maze, starting at the second day, according to the study authors.

However, investigators reported that the SAMP8 group did not have consistent changes in latency when compared to the first day of the maze. Further, the latency was higher than the control group from the second day and onward. Similar results were seen with the group that was treated with trigonelline.

When conducting the probe trial, which occurred on day 8, the SAMP8 mice had a significant decrease in time spent in the target quadrant and crossing number when compared to the control group of mice, according to the results of the study. However, investigators reported that the mice treated with trigonelline had significantly increased time in the target quadrant and the crossing number compared to the untreated SAMP8 mice.

Additionally, in the hippocampus of mice, trigonelline suppressed neuroinflammation and increased neurotransmitter release, which may have contributed to the improvements in cognitive function. According to the investigators, neuroinflammation is a risk factor of developing cognitive accelerated aging. Suppressing inflammation could be the key to decreasing cognitive decay.

Trigonelline was observed to reduce TNFα and interleukin (IL)-6 protein levels in SAMP8 mice. It was also found to suppress lipopolysaccharide (LPS)-induced TNFα expression, according to the study authors.

Investigators also analyzed whole–genome data for the mice, both in the nontreated and treated groups. They identified that trigonelline’s primary bioactivity in anti-inflammatory function was significantly impactful on chemokine signaling pathways, IL5 signaling pathway, IL9 signaling pathway, T-cell receptor/Ras pathways, and additional clusters.

Furthermore, the treatment led to decreases in the expression levels of proinflammatory cytokines and chemokines that are essential for neuroinflammation, according to the study investigators. Additionally, they reported the treatment released neurotransmitters, which enhanced the memory and learning functions in the aging mice models and included dopamine, noradrenaline, and serotonin.

Investigators said that these results were promising, indicating that trigonelline could help to alleviate cognitive decline associated with aging. The study authors suggested that trigonelline could be used a supplementary treatment; however, further investigations need to be conducted into validating these findings, especially in the underlying mechanisms in the bioactivities of trigonelline.

Reference

Aktar S, Ferdousi F, Kondo S, Kagawa T, Isoda H. 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. 2023;10.1007/s11357-023-00919-x. doi:10.1007/s11357-023-00919-x