Natural Products Screening for the Identification of Selective Monoamine Oxidase-B Inhibitors.

AIMS: Monoamine oxidase-B inhibitors (MAO-BIs) are used for the initial therapy of Parkinson's disease. Also, MAO-BIs have shown to be effective neuroprotective agents in several neurodegenerative diseases. However, some concerns exist regarding the long-term use of these compounds. Meanwhile, natural compounds showed potential MAO-B selective inhibitions. To date, few selective natural MAO-BIs have been identified. Therefore, the current study is designed to identify plants with potent and specific MAO-B inhibition.

STUDY DESIGN: In this work, we utilized high throughput screening to evaluate the different plants ethanolic extract for their effectiveness to inhibit recombinant human ( h )MAO-A and h MAO-B and to determine the relative selectivity of the top MAO-BI.

METHODOLOGY: Recombinant human isozymes were verified by Western blotting, and the 155 plants were screened. A continuous fluorometric screening assay was performed followed by two separate h MAO-A and h MAO-B microtiter screenings and IC50 determinations for the top extracts.

RESULTS: In the screened plants, 9% of the extracts showed more than 1.5-fold relative inhibition of h MAO-B (RIB ) and another 9% showed more than 1.5-fold relative inhibition of h MAO-A. The top extracts with the most potent RIB s were Psoralea corylifolia seeds, Phellodendron amurense bark, Glycyrrhiza uralensis roots, and Ferula assafoetida roots, with the highest RIB of 5.9-fold. Furthermore, extensive maceration of the promising extracts led to increase inhibitory effects with a preserved RIB as confirmed with luminescence assay. The top four extracts h MAO-BIs were equally potent (IC50 = 1.3 to 3.8 μg/mL) with highly significant relative selectivities to inhibit h MAO-B (4.1- to 13.4-fold).

CONCLUSION: The obtained results indicate that Psoralea corylifolia seeds, Ferula assafoetida, Glycyrrhiza uralensis roots, and Phellodendron amurense ethanolic extracts have selective inhibitions for human MAO-B. Investigating these plant extracts as natural resources for novel selective MAO-BIs may lead to the development of molecules that can be used in the therapeutic management of neurodegenerative diseases including Parkinson's disease.