A recent study conducted by the Technische Universität Dresden in Germany and the National Institute of Psychiatry “Ramon de la Fuente Muñiz” in Mexico has revealed new insights into the potential impact of apples on brain health. The study focused on the neurogenic properties of specific phytochemicals found in apple peel and flesh, namely quercetin and 3,5-dihydroxybenzoic acid (3,5-DHBA).
The researchers delved into the concept of brain plasticity, which refers to the brain’s ability to undergo structural and functional changes. They specifically explored a form of brain plasticity called adult hippocampal neurogenesis, which involves the generation of new neurons throughout life. Flavonoids, which are abundant in fruits and vegetables, have long been recognized for their potential to influence cognitive processes. However, previous studies primarily focused on flavonoids from sources other than apples.
Quercetin, the most abundant flavonoid in apple peel, was found to have a complex role in neurogenesis. At high concentrations, it was anti-proliferative, inhibiting the growth of neural precursor cells. However, at lower concentrations, it exhibited pro-neurogenic effects, promoting the survival and differentiation of these cells. In vivo experiments further supported these findings, showing an increase in the generation of new neurons with the administration of quercetin.
To understand the mechanisms behind quercetin’s pro-neurogenic effects, the researchers conducted RNA microarray analysis. They discovered significant changes in gene expression related to oxidative stress, cell cycle, endogenous antioxidative activity, and cell survival pathways. The activation of the PI3K-AKT and NRF2-KEAP1 pathways was proposed to contribute to quercetin’s pro-neurogenic effects.
While quercetin is primarily found in apple peel, the study also investigated the pro-neurogenic potential of compounds in apple flesh. They identified 3,5-DHBA as a significant contributor to neurogenesis in the flesh. Despite lower levels of flavonoids compared to the peel, apple flesh exhibited similar pro-neurogenic properties. The neuroprotective effects of 3,5-DHBA were found to be distinct from flavonoids, emphasizing its unique role in promoting neurogenesis.
Further experiments revealed that 3,5-DHBA significantly increased the proliferation of neural precursor cells and the generation of new neurons. In vivo experiments with adult mice confirmed these findings, showing a notable rise in the number of proliferating neural precursor cells and newborn neurons in the dentate gyrus after administering 3,5-DHBA. The effects of 3,5-DHBA were concentration-dependent, enhancing the maturation rate of newborn neurons.
The study also identified hydroxycarboxylic acid receptor 1 (HCAR1) as a putative receptor for 3,5-DHBA. HCAR1 is expressed on neural precursor cells, suggesting a direct mode of action for 3,5-DHBA.
In summary, this comprehensive study highlights the pro-neurogenic potential of specific compounds found in apples. Quercetin from the peel and 3,5-DHBA from the flesh not only promote the proliferation of neural precursor cells but also support their survival, differentiation, and maturation into functional neurons. The study provides insight into the intricate relationship between dietary compounds and neurogenesis, particularly through the involvement of the PI3K-AKT and NRF2-KEAP1 pathways. As scientists continue to explore the link between diet and brain health, apples emerge as a promising natural source of bioactive compounds with potential implications for cognitive well-being.