RESUMEN
Cognitive impairments can be devastating for quality of life, and thus, preventing or counteracting them is of great value. To this end, the present study exploits the potential of the plant Rhodiola rosea and identifies the constituent ferulic acid eicosyl ester [icosyl-(2E)-3-(4-hydroxy-3-methoxyphenyl)-prop-2-enoate (FAE-20)] as a memory enhancer. We show that food supplementation with dried root material from R. rosea dose-dependently improves odor-taste reward associative memory scores in larval Drosophila and prevents the age-related decline of this appetitive memory in adult flies. Task-relevant sensorimotor faculties remain unaltered. From a parallel approach, a list of candidate compounds has been derived, including R. rosea-derived FAE-20. Here, we show that both R. rosea-derived FAE-20 and synthetic FAE-20 are effective as memory enhancers in larval Drosophila. Synthetic FAE-20 also partially compensates for age-related memory decline in adult flies, as well as genetically induced early-onset loss of memory function in young flies. Furthermore, it increases excitability in mouse hippocampal CA1 neurons, leads to more stable context-shock aversive associative memory in young adult (3-month-old) mice, and increases memory scores in old (>2-year-old) mice. Given these effects, and given the utility of R. rosea-the plant from which we discovered FAE-20-as a memory enhancer, these results may hold potential for clinical applications.
Asunto(s)
Ácidos Cumáricos/farmacología , Ésteres/farmacología , Memoria/efectos de los fármacos , Rhodiola/química , Factores de Edad , Animales , Abejas , Conducta Animal/efectos de los fármacos , Región CA1 Hipocampal/citología , Región CA1 Hipocampal/efectos de los fármacos , Suplementos Dietéticos , Drosophila melanogaster , Miedo/efectos de los fármacos , Larva/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Extractos Vegetales/farmacología , Especificidad de la EspecieRESUMEN
Short-boiled aqueous extract from leaves of Cistus incanus L. ssp. incanus (CIT) dose-dependently inhibit the enzymatic activities of both alanyl aminopeptidase (APN, CD13, EC 3.4.11.2) and dipeptidylpeptidase IV (DP IV, CD26, EC 3.4.14.5). This inhibition is not reversible and very likely results from a covalent binding of reactive compounds to the enzymes. Furthermore, we show that aqueous CIT extracts decrease the DNA-synthesis of human T cells and mononuclear cells and inhibit the proliferation rate of the human T cell line KARPAS-299 in a dose-dependent manner. Data are presented suggesting that the antiproliferative effects of CIT extracts are due to their strong cytotoxic activity.