Abstract
AimsMonoamine 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 DesignIn 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 hMAO-B and to determine the relative selectivity of the top MAO-BI.MethodologyRecombinant human isozymes were verified by Western blotting, and the 155 plants were screened. A continuous fluorometric screening assay was performed followed by two separate hMAO-A and hMAO-B microtiter screenings and IC50 determinations for the top extracts.ResultsIn the screened plants, 9% of the extracts showed more than 1.5-fold relative inhibition of hMAO-B (RIB) and another 9% showed more than 1.5-fold relative inhibition of hMAO-A. The top extracts with the most potent RIBs 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 hMAO-BIs were equally potent (IC50= 1.3 to 3.8 μg/mL) with highly significant relative selectivities to inhibit hMAO-B (4.1- to 13.4-fold).ConclusionThe 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.
Highlights
In Parkinson’s disease and depression monoamine oxidase inhibitors (MAO-AIs and MOAIs) have been used in the therapy of these diseases
In the screened plants, 9% of the extracts showed more than 1.5-fold relative inhibition of hMAO-B (RIB) and another 9% showed more than 1.5-fold relative inhibition of hMAO-A
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
Summary
In Parkinson’s disease and depression monoamine oxidase inhibitors (MAO-AIs and MOAIs) have been used in the therapy of these diseases. That MAO-B elevation [1,5] with the co-localized of active MAO-A isozyme can potentially aggravate oxidative stress in the aging patients. Both MAOs activities produce abnormally high amounts of hydrogen peroxide (H2O2) and aldehydes that are neurotoxic. Those by-products potentially damage proteins, nucleic acids, lipids and activate apoptotic pathways [6]. Other oxidative stress defense enzymes may become limited with the overwhelming reactive species produced These toxic byproducts, of active MAO-B, can potentially accumulate in neurons and astrocytes leading to cell death and aggravating neurodegeneration
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