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Inhibition of monoamine oxidase (MAO) by β-carbolines and their interactions in live neuronal (PC12) and liver (HuH-7 and MH1C1) cells


Web link: linkinghub.elsevier.com/retrieve/...

Pages: 403-410

Abstract

Interactions among monoamine oxidase (MAO) inhibitors in drugs, botanicals, and dietary supplements may lead to unpredictable neurochemical dysfunction due to excessive inhibition or therapeutic invali- dation. Often recombinant MAO or brain tissue homogenates have been used to evaluate MAO inhibitors such as the b-carboline alkaloids (harmane, harmine, harmaline, and harmalol). However, there is a lack of cellular systems for evaluation of MAO activity, which represents a more advanced in vitro model com- pared to recombinant enzymes or tissue lysates. Using kynuramine assays, intracellular MAO inhibition by b-carbolines was measured in PC12 (rat pheochromocytoma), MH1C1 (rat liver), and HuH-7 (human liver) cell lines, which were compared with human recombinant MAO and cell lysates. b-Carbolines (1 lM, 90 min incubations) inhibited MAO by 40–99% in live PC12 cells where MAO A was the active iso- form, and <12% in HuH-7 and MH1C1 cells where MAO B was primarily active. The combination index (CI), which serves as a quantitative indicator of pharmacological interactions, was determined for harma- line/harmine (CI, 1.01–1.25) and methylene blue/harmine (CI, 0.74–1.07) in PC12 cells. Overall, this study illustrates applications of cell-based in vitro assay platforms to gain a comprehensive understanding of intracellular MAO inhibitors and their interactions.