Secondary metabolites of edule fruits and vegetables display MAO-B inhibitory activity

Monoamine oxidase (MAO) are mitochondrial membrane-bound enzymes that catalyze the oxidative deamination of many neurotransmitters and biogenic amines. There are two MAO isoenzymes: MAO-A and MAO-B, which differ in their substrate specificities, tissue localizations and inhibitor sensitivities. The inhibition of MAO-B is an important target in the prevention and the treatment of neurodegenerative diseases such as Parkinson, due to its role in the regulation of dopaminergic neurotransmission. Increased activity of MAO-B has also been linked to oxidative damage in the brain because of the production of reactive oxygen species. Plants produce secondary metabolites with many known biological activities, including the inhibition of MAO. This activity has been studied mostly in medicinal and hallucinogenic plants, while the most commonly consumed fruits and vegetables are often overlooked. We investigated the MAO-B inhibitory activity of 19 different fruits and vegetables, analyzing their biological activity on MAO-B through an in vitro assay based on luminescence. Preliminary analysis suggested that this activity is produced by secondary metabolites. The most active fruits and vegetables found were cucumber, red chicory, sweet cherry, shallot, lettuce and sweet pepper. We then carried out further analysis to identify the metabolites responsible for this activity in two selected species: lettuce and sweet cherry. The metabolome of lettuce was investigated through UPLC-MS analysis. Data revealed that the main secondary metabolites belong to the classes of hydroxycinnamic acids and to the class of sesquiterpene lactones, such as derivatives of lactucopicrin and lactucin, compounds known for having many biological activities on humans. Furthermore, previous HPLC-DAD analysis elucidated the metabolome of sweet cherries and allowed us to investigate in more detail the MAO-B inhibitory activity of this fruit, in particular we focused on the cultivar Roana. An artificial simplified phytocomplex was made to mimic the composition of sweet cherry on the basis of its pholyphenols content. We found that hydroxycinnamic acids are metabolites active on MAO at the concentrations found in fruits, while quercetins are not. We also hypothesized that ascorbic acid might instead suppress the inhibition of MAO-B. These results suggest that fruits and vegetables provide molecules potentially active on human MAO-B, thus stressing the role of fruits and vegetables in the protection from oxidative stress.