Natural compounds found in apples and other fruits may help to stimulate the production of new brain cells, which could have implications for learning and memory, according to a new study by researchers at the University of Queensland, and the German Center for Neurodegenerative Diseases. Their work in cultured cells and in live mice indicated that quercetin, the most abundant flavanol compound in apple peel, together with other compounds found in apples, were pro-neurogenic. The results of their studies, described in Stem Cell Reports, suggest that these natural fruit compounds may act in synergy to promote neurogenesis and brain function when given in high concentrations.

In their paper, titled “Apple Peel and Flesh Contain Pro-neurogenic Compounds,” the team, headed by Tara Louise Walker, PhD, at the University of Queensland, and Gerd Kempermann, at the German Center for Neurodegenerative diseases, concluded, “This work shows that both flavonoids and 3,5-dihydroxybenzoic acid are pro-neurogenic, not only by activating precursor cell proliferation but also by promoting cell cycle exit, cellular survival, and neuronal differentiation.”

Apart from being a source of energy, food is known to influence an individual’s overall fitness, the researchers noted. “A growing number of studies have demonstrated the health benefits of phytochemicals, the chemical substances found in plants.” So, as the authors commented, the aphorism ‘An apple a day keeps the doctor away,’ may in fact have some biological truth. In fact plant phytonutrients, such as resveratrol in red grapes or epigallo-catechin-3-gallate (EGCG) in green tea, are chemical compounds that have been shown to have positive effects on different parts of the body, including the brain.

Active dietary compounds are vital for maintaining cognitive function, they continued. “Adult hippocampal neurogenesis is a particular form of brain plasticity in which functional neurons are generated throughout life and integrated into the existing circuitry, thereby mediating particular forms of learning and memory.” And flavonoids, which are phytonutrients found in fruits and vegetables, can modulate molecular signaling pathways that influence these cognitive processes, the team continued.

Given that applies are one of the most widely consumed fruits in the world, Walker, Kempermann and colleagues were interested to find out whether this fruit contains substances that might sustain or promote adult hippocampal neurogenesis. They first looked at quercetin, the most abundant flavonoid in apple peel, and then broadened the investigation to identify other pro-neurogenic factors in apples.

The results of their studies confirmed that high concentrations of phytonutrients from apples stimulated the generation of new neurons. Experiments showed that laboratory-grown stem cells from adult mouse brains generated more neurons and were protected from cell death when the phytonutrients quercetin or another compound, dihydroxybenzoic acid (DHBA), were added to the cultures. “… these findings indicate that quercetin can act pro-neurogenically even in the presence of growth factors, which normally maintain neural precursor cells (NPCs) in an undifferentiated and proliferative state in vitro,” they wrote. “Using a bioassay-guided fractionation approach we also identified additional pro-neurogenic compounds in apple flesh that were not related to flavonoids … We found that 3,5-DHBA not only increases NPC [neural precursor cell] proliferation and neurogenesis, but also increases the maturation rate of these newborn cells.”

Hippocampal precursor cells differentiate into neurons when treated with the apple-derived compound DHBA. [German Center for Neurodegenerative Diseases, Dresden, Germany]

Subsequent tests in mice showed that in distinct structures of the adult brain associated with learning and memory, stem cells multiplied and generated more neurons when the mice were given high doses of quercetin or DHBA. The effects on neurogenesis were comparable to effects seen after physical exercise, which is a known stimulus for neurogenesis.

In their report the team indicated that the effects of quercetin on factors such as survival and differentiation of adult hippocampal NPCs, both ex vivo and in vivo, are similar to the effects that have previously been reported for compounds such as resveratrol and EGCG. “Natural compounds such as these, which are abundant in widely consumed fruits and vegetables, might therefore contribute to a beneficial effect on neurogenesis and brain function as part of broader environmental influences,” they concluded.

Future studies will be required to determine if these and other phytonutrients can enhance learning and cognitive function in animal models and in humans.

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