Inhibition of rat brain monoamine oxidase activities by psoralen and isopsoralen: Implications for the treatment of affective disorders

Psoralen and isopsoralen. furocoumarins isolated from the plant Psoralea corylifolia L., were demonstrated to exhibit in vitro inhibitory actions on monoamine oxidase (MAO) activities in rat brain mitochondria, preferentially inhibiting MAO-A activity over MAO-B activity. This inhibition of enzyme activities was found to be dose-dependent and reversible. For MAO-A, the IC50 values are 15.2+/-1.3 muM psoralen and 9.0+/-0.6 muM isopsoralen. For MAO-B, the IC50 values are 61.8+/-4.3 muM psoralen and 12.8+/-0.5 muM isopsoralen. Lineweaver-Burk transformation of the inhibition data indicates that inhibition by both psoralen and isopsoralen is non-competitive for MAO-A. The K-i values were calculated to be 14.0 muM for psoralen and 6.5 muM for isopsoralen. On the other hand, inhibition by both psoralen and isopsoralen is competitive for MAO-B. The K-i values were calculated to be 58.1 muM for psoralen and 10.8 muM for isopsoralen. These inhibitory actions of psoralen and isopsoralen on rat brain mitochondrial MAO activities are discussed in relation to their toxicities and their potential applications to treat affective disorders.