Selectivity of Dietary Phenolics for Inhibition of Human Monoamine Oxidases A and B.
Level 5 - mechanism / opinion, no new human data
In vitro biochemical assay using recombinant enzymes (no human subjects)
PubMed 30809547 · doi:10.1155/2019/8361858
What was done
Human recombinant monoamine oxidases A and B (MAO-A and MAO-B) were evaluated in an in vitro assay measuring kynuramine metabolism to 4-hydroxyquinoline. Several dietary phenolics (curcumin, guaiacol, isoeugenol, pterostilbene, resveratrol, and zingerone) and polyphenol glucosides (resveratrol 4'-glucoside, resveratrol 3-glucoside, and pterostilbene 4'-glucoside) were tested to establish inhibitory concentrations (IC50), selectivity ratios (MAO-A/MAO-B IC50 ratio), and mechanisms of inhibition.
What was found
Baseline enzyme kinetics showed Vmax values of 10.2 ± 0.2 nmol/mg/min (Km 23.1 ± 0.8 μM) for MAO-A and 7.35 ± 0.69 nmol/mg/min (Km 18.0 ± 2.3 μM) for MAO-B. All parent compounds significantly inhibited both enzymes at expected gastrointestinal concentrations, except zingerone, which inhibited only MAO-A. Resveratrol and isoeugenol selectively inhibited MAO-A, with IC50 values of 0.313 ± 0.008 μM (selectivity index 50.5) and 3.72 ± 0.20 μM (selectivity index 27.4), respectively. Pterostilbene selectively inhibited MAO-B, with an IC50 of 0.138 ± 0.013 μM (selectivity index 0.0103). Resveratrol (for MAO-A) and pterostilbene (for MAO-B) exhibited competitive, time-independent inhibition. Resveratrol 4'-glucoside inhibited MAO-A, but neither it, resveratrol 3-glucoside, nor pterostilbene 4'-glucoside inhibited MAO-B.
Why it matters
The findings show that dietary stilbenes have distinct sub-micromolar selectivity for human MAO isoforms in vitro, with resveratrol favoring MAO-A and pterostilbene favoring MAO-B. This provides baseline biochemical selectivity data for exploring dietary compounds in conditions associated with elevated MAO activity.
Limits
This study is entirely in vitro using recombinant enzymes; it does not measure in vivo bioavailability, tissue distribution, blood-brain barrier penetration, or clinical efficacy in humans. IC50 values for curcumin, guaiacol, and zingerone were not detailed in the abstract.
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