Identification and occurrence of β-carboline alkaloids in raisins and inhibition of monoamine oxidase (MAO)

Abstract

Monoamine oxidase (MAO) is a mitochondrial enzyme involved in the oxidative catabolism of neurotransmitters and xenobiotic amines, including vasopressor and neurotoxic amines, and a current target for antidepressant and neuroprotective drugs. Raisin extracts and homogenates exhibited reversible in vitro inhibition of MAO isozymes, particularly MAO-A, suggesting the presence of MAO-inhibiting substances. Chromatographic and spectrometric studies showed the occurrence of aromatic β-carboline alkaloids in raisins, and norharman and harman were identified as the key contributors to MAO inhibition. On average, harman ranged from 6 to 644 ng/g and norharman from 2 to 120 ng/g. Several technological variables appeared to determine the presence of these compounds in raisins. Dark-brown raisins (i.e., sun-dried) contained much higher levels than golden raisins. Tetrahydro-β-carboline-3-carboxylic acid compounds that are direct precursors of aromatic β-carbolines were also identified in raisins and appeared in a higher amount, reaching up to 50 μg/g. β-Carbolines were isolated from raisins and acted as good competitive inhibitors of MAO-A (harman) and MAO-B (norharman) isozymes. These results suggest that β-carboline alkaloids and perhaps raisins containing a high level of β-carbolines might exhibit potential activity as MAO inhibitors. The results also show that some raisins can be a source of dietary exposure to bioactive β-carbolines. © 2007 American Chemical Society.