Methylpiperate derivatives from Piper longum and their inhibition of monoamine oxidase

Abstract

We have previously reported that piperine, a known piperidine alkaloid from Piper longum, competitively inhibited mouse brain MAO-A and MAO-B activities. Piperine also showed in vivo antidepressant-like activity against the tail suspension test. In the present study, we further expanded on the identification of MAO inhibitors from the fruit of P. longum. Activity-guided fractionation of a methylene chloride soluble extract led to the isolation of three known piperine-related compounds, methylpiperate (1), guineensine (2), and piperlonguminine (3). Of these, methylpiperate (1) and guineensine (2) showed significant MAO inhibitory activities with IC₅₀ values of 3.6 and 139.2 μM, respectively. Furthermore, methylpiperate (1) exhibited a selective inhibitory effect against MAO-B (IC₅₀ value: 1.6 μM) than MAO-A (IC₅₀ value: 27.1 μM). The kinetic study using the Lineweaver-Burk plots analysis suggested that methylpiperate (1) competitively inhibits MAO-A and MAO-B activities with the Ki values of 23.5 and 1.3 μM, respectively.