Screening of monoamine oxidase inhibitory compounds from Tartary buckwheat through UPLC-MS/MS profiling, in silico analysis and other experimental investigations

Abstract Central fatigue (CF) affects negatively cognition, emotion and physical performance. Monoamine oxidase (MAO), a key mitochondrial bound enzyme, modulates the levels of neurotransmitters, which is closely associated with the development of CF. This study follows recent attempts to discover natural MAO inhibitory compounds from foods, focusing on Tartary buckwheat. UPLC-MS/MS profiling and other experiments revealed 18 key polyphenols from Tartary buckwheat as MAO inhibitors, with six being reported for the first time. Network pharmacology and molecular docking studies indicated that quercetin, ellagic acid, emodin, galangin, kaempferol, morin and butein may be the MAO inhibitors. In vitro MAO inhibition assays confirmed that quercetin was the most potent inhibitor (IC₅₀=3.982-4.386 μM). Animal-friendly behavioral testing, neurotransmitter profiling, transcriptomic analysis and western blot experiments showed that quercetin significantly ameliorated behaviors of fatigue-dominant phenotypes, regulated the levels of neurotransmitters and alleviated CF via the PI3K/AKT signaling pathway. Accordingly, Tartary buckwheat provides anti-CF polyphenols.