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. 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 30 days of oral administration of TG at the dose of 5 mg/kg/day, the mice were trained in Morris Water Maze task. 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. Further, a nonlinear dimensionality reduction technique, Uniform Manifold Approximation and Projection (UMAP), was applied to identify clusters of functions that revealed TG primarily regulated pathways related to inflammation, followed by those involved in neurotransmitter release. In addition, a protein-protein interaction network analysis indicated that TG may exert its biological effects through negatively modulating Traf6-mediated NF-κB activation. Finally, ELISA test showed that TG treatment significantly decreased proinflammatory cytokines- TNFα and IL6 and increased neurotransmitters- dopamine, noradrenaline, and serotonin in mouse hippocampus. Altogether, our integrated bio-cognitive approach highlights the potential of TG in alleviating age-related memory and spatial impairment.

[Studies on antihypertensive effect of Luobuma (Apocynum venetum L.) leaf extract (3)].

To clarify the mechanisms underlying the antihypertensive effect of Luobuma (Apocynum venetum L. (Apocynaceae)) leaf extract (LLE), we investigated the vasodilator effect of LLE in the rat mesenteric vascular bed, which plays an important role in changes in peripheral resistance and thus the regulation of blood pressure. In the perfused mesenteric vascular bed with active tone and intact endothelium, perfusion of LLE (0.1 ng to 100 mg/ml for 15 min) caused dose-dependent vasodilation, which was abolished by chemical removal of the endothelial layer with perfusion of sodium deoxycholate, but not by N(G)-nitro-L-arginine-methyl ester (L-NAME), a competitive inhibitor of nitric oxide (NO), which instead increased the effect. The LLE-induced vasodilation was partially inhibited by high K(+)-containing Krebs solution and tetraethylammonium (a K(+) channel blocker) and completely by the combination of L-NAME and high K(+)-Krebs solution. However, atropine (a muscarinic acetylcholine receptor antagonist) did not affect the vasodilation. These results suggest that the vasodilation induced by LLE is endothelium-dependent and mediated by endothelium-derived hyperpolarizing factor, which involves the activation of K(+)-channels. The higher concentrations of LLE may enhance NO production/release to cause vasodilation.