Memory Loss

Monoamine oxidase (MAO) is an enzyme involved in the degradation process for various monoamines released by neurons and glial cells, including dopamine, serotonin and norepinephrine (NE).

All of which are crucial to brain function in various ways.

There are two types of MAO, Type A and Type B.  Slowing down (inhibiting) the breakdown of these enzymes allows their number to increase which in turn benefits cognitive function as well as psychological disorders depression and anxiety and ADHD.

Monoamine Neurotransmitters Include:

  • Dopamine
  • Serotonin
  • Adrenaline
  • Dimethyltryptamine (DMT)
  • Melatonin
  • Noradrenalin
  • B-phenylethylamine (PEA)
  • Benzylamine

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

1. Amur Cork Tree (Phellodendron Amurense)

MAO-B Inhibition Very High (IC50 <.07 mg/ml)

Amur cork tree is one of the 50 fundamental Chinese herbs. It’s commonly used for it’s sedative, muscle relaxant, antiarrhythmic, positive inotropic, hypotensive, and antibacterial actions. 

 Phellodendron amurense (aka Amur cork tree; family Rutaceae) is a meagerly investigated Chinese medicinal plant. In our study, its bark ethanolic extract clearly was a selective hMAO-BI as its potent inhibition was previously spectrophotometrically confirmed []. The plant constituted alkaloids such as phellodendrine, palmatine, jatrorrhizine, and berberine [,] where the later displayed safe antidepressant-like activities in mice by the possible mechanism MAO-A inhibition and increasing DA, NE and serotonin brain levels [,]. PAB is high in the flavone tetramethyl-o-scutellarin, and the triterpenoids limonoids []. Limonoid obacunone was found neuroprotective in glutamate-induced neurotoxicity in vitro []. In clinical studies, PAB extract supplement safely reduced cortisol [], and relieved mild anxiety in women []. Also, PAB inhibited pro-inflammatory cytokines [,] and protected from prostate tumors progression [], property found in some MAO-AIs []. Based on our results and literature, there is a lack of knowledge on MAO-B inhibition and selectivity benefits of PAB extracts and phytochemicals. Further studies on PABEE as MAO-BI source for PD are highly recommended.

2. Gan Cao (Glycyrrhiza Uralensis Root)

MAO-B Inhibition Very High (IC50 <.07 mg/ml)

Gan Cao is a type of licorice (same genus), and is used in much the same way. Its traditional uses involves female disorders, digestive disorders, ulcers, and heart arrythmias. One of the most interesting sue of this plant, is as a “harmonizer” of other medicinal plants. In Chinese traditional medicine this is one of the main herbs used in formulas for its ability to improve the outcomes of other plants.

The roots of Glycyrrhiza uralensis (aka Chinese licorice; family Leguminosae) is another commonly used medicinal plant in traditional Chinese and natural medicine. Our new finding that GUREE inhibits hMAO-B selectively is supported by our previous finding for its hMAO-B inhibition []. Interestingly, GUR was more selective than Glycyrrhiza glabra in our screen. Reported Glycyrrhiza uralensis different active constituents from other Glycyrrhiza genuses may influence its MAO-B selective inhibition []. GUR contains unique phytochemicals including isoprenylated phenolics [] flavonoids, chalcones, and triterpene saponins []. Chalcone isoliquiritigenin, is an inhibitor for MAO-B [] with multifunctional anti-inflammatory, antioxidant, cytoprotective [] cellular detoxification system activator [] and anti-apoptotic [] anti-amyloid-β toxicity [] neuroprotective properties. GUR total flavonoid extracts showed neurogenesis protective effect in depressed rats model []. The flavonoid liquiritin showed antioxidant and antiapoptotic neuroprotective effects in mice [] and ameliorated depression in rat model []. Its benzopyran dehydroglyasperin-C also showed neuroprotection []. Xiaoyaosan, a traditional herb combination containing GUR for chronic depression, was effective in both animal models and clinical trials [,]. Other multifunctional properties of GUR constituents included reducing pro-inflammatory cytokines, nitric oxide, reactive oxygen species, lipid peroxidation [], and mitochondrial impairment []. Interestingly, GUREE reports covered its chemopreventive [] and anti-diabetic properties []. Therefore, specifically investigating GUREE as a selective MAO-BI could be beneficial.

3. Psoralea Fruit Babchi (Psoralea Corylifolia)

MAO-B Inhibition Very High (IC50 <.07 mg/ml)

Psoralea fruit is a lesser known Ayurvedic and Traditional Chinese medicinal plant species. It was used in the past for conditions like vitiligo and other skin related conditions. Recently it has received a lot of attention for its MAO inhibiting properties, and is suggested to be a norepinephrine, re-uptake inhibitor.  

In addition, the seeds of Psoralea corylifolia (aka, Bu Gu Zhi or Babchi; family Leguminosae) are important in traditional Chinese and Ayurvedic medicines []. PCSEE was one of the most potent and selective hMAO-BI using our fluorometric screening assay. Our PCS findings are supported by our previous investigations on its hMAO-B inhibitory potency tested spectrophotometrically [], and its selectivity for hMAO-B using a luminescence assay []. Previous PCS screened extracts for active constituents revealed that the ethanolic extract composes more medically active compounds than some other PCS extracts, which makes it a better candidate for novel phytomedicines []. PSCEE is rich in benzopyrone structure constituents including coumarins and flavonoids. PCS furocoumarins psoralen and isopsoralen showed rat MAOs activities inhibitions [], which were supported by total furocoumarins potent antidepressant effects on mice []. PCS also contains isoflavones, which have been used as dietary supplements in various diseases, including osteoporosis, cognitive dysfunction, cardiovascular disease, and inflammation [], which are close to PCS multifaceted properties []. We previously investigated bavachinin and genistein flavonoids constituents of PCS. Bavachinin exhibited a selective hMAO-B inhibition [] while isoflavone genistein was similarly potent but less selective against hMAO-B []. Moreover, PCSEE contains monoterpenes that protected against the MAO-B substrate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) SN cell damage and MPTP-induced motor deficits in PD model [], inhibited DA and norepinephrine (NE) transporters [], and showed antidepressant effects with catecholamine neurotransmitters regulation [,]. The PCS extracts were also neuroprotective against the MPTP precursor MPP+ [] and the nitropropionic acid (3-NP) induced cytotoxicity and mitochondrial dysfunction []. Although the seeds are used in dermatological disorders health supplements [] and increasingly investigated on in vitro and animal models, the extract and its phytochemicals clinical effects on degenerative diseases are yet to be clinically considered. From our results, the observed association between PCS constituents MAO-B inhibitions and the extracts neuroprotection in the previous reports suggests more investigations for potential beneficial PCS phytochemicals for PD.

4. Ferula assafoetida roots

MAO-B Inhibition Very High (IC50 <0.07 mg/ml)

This resin has been used as a spice and a phytomedicine around the globe for centuries. In the folklore medicine, it is mostly used in asthma, gastrointestinal disorders, and neuronal disorders []. In recent reports, the resin improved memory and learning in rats [], and exhibited neuroprotection and nerve stimulation in mice peripheral neuropathy [], and anticonvulsant properties []. FAR contains bioactive phytochemicals such as polysulfides, sesquiterpenes, sesquiterpene-coumarins, diterpenes, phenolics, and flavonoids [,]. Its coumarin umbelliprenin showed anti-inflammatory properties [], while ferulic acid showed anti-atherosclerotic, antioxidant, and neuroprotective properties [] and became a candidate for AD []. Therefore, investigations on the resin concerning PD need to be considered.

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

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4898948/