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Sci Adv. 2018 Oct 24;4(10):eaat6994. doi: 10.1126/sciadv.aat6994. eCollection 2018 Oct.

Memory enhancement by ferulic acid ester across species.

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Leibniz Institute for Neurobiology, Department Genetics of Learning and Memory, Magdeburg, Germany.
Free University Berlin, Institute of Neurobiology, Berlin, Germany.
Precarpathian National University, Department of Biochemistry, Ivano-Frankivsk, Ukraine.
Leibniz Institute of Plant Biochemistry (IPB), Department of Bioorganic Chemistry, Halle (Saale), Germany.
Otto von Guericke University, Medical Faculty, Magdeburg, Germany.
Otto von Guericke University, Medical Faculty, Institute for Pharmacology and Toxicology, Magdeburg, Germany.
Center for Behavioral Brain Sciences (CBBS), Otto von Guericke University, Magdeburg, Germany.
German Center for Neurodegenerative Diseases (DZNE), Molecular Neuroplasticity Group, Magdeburg, Germany.
University of Würzburg, Biocenter Am Hubland, Department of Genetics and Neurobiology, Würzburg, Germany.
Otto von Guericke University, Institute of Experimental Internal Medicine, Magdeburg, Germany.
Otto von Guericke University, Institute of Biology, Magdeburg, Germany.


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.

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