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

Abstract

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 hMAO-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 hMAO-A and hMAO-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 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). 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.

The Possible Therapeutic Effects of Some Medicinal Plants for Chronic Cough in Children

“…The oleogum resin of F. assa-foetida also showed antioxidant, antiviral, antifungal, antispasmodic, and antihypertensive effects in pharmacological studies [ 90 ]. It has been documented that F. assa-foetida resin can potentially inhibit monoamine oxidase B (MAO-B), and it can be used in the therapy of neurodegenerative diseases such as Parkinson's and Alzheimer's diseases [ 94 ].…”

Herbal Medicine as Neuroprotective Potential Agent in Human and Animal Models: A Historical Overview

“…The researchers stated that oleo gum-resin of asafoetida could improve renewal and re-myelination and declines the rate of lymphocyte penetration in the neuropathic muscle in rats; thus, its action as a neuroprotective and nerve simulative agent in peripheral neuropathy (37). It is scientifically proved that it can also use in the treatment of neurodegenerative ailments like Parkinson's and Alzheimer's diseases (38). In the behavioral model, inactive prevention test, the lesser quantity of extract (200 mg) cannot increase memory while in high quantity (400mg), it improved memory in Wistar rats (39).…”

Neuroprotective potency of some spice herbs, a literature review

“…It has also been documented that oleo gum resin of F. asafoetida can enhance regeneration and re-myelination and decreases the rat of lymphocyte infiltration in the neuropathic tissue in mice; therefore it acts as a neuroprotective and nerve simulative agent in peripheral neuropathy 64 . Scientific evidences have also shown that F. asafoetida resin can potentially inhibit monoamine oxidase B (MAO-B) and it can be used in the therapy of neurodegenerative diseases such as Parkinson ' s and Alzheimer's diseases 65 . Meanwhile, Ferula asafoetida has been reported to have acetylcholinestrase (AChE) inhibiting property in vitro assay and in vivo on snail nervous system.…”

“… 64 Scientific evidences have also shown that F. asafoetida resin can potentially inhibit monoamine oxidase B (MAO-B) and it can be used in the therapy of neurodegenerative diseases such as Parkinson ' s and Alzheimer's diseases. 65 Meanwhile, Ferula asafoetida has been reported to have acetylcholinestrase (AChE) inhibiting property in vitro assay and in vivo on snail nervous system. Researchers have proposed that memory increasing effect of Ferula asafoetida could be attributed to inhibitory effect of this plant on AChE in the rat brain.…”