Natural Products Inhibitors of Monoamine Oxidases—Potential New Drug Leads for Neuroprotection, Neurological Disorders, and Neuroblastoma

Chaurasiya, Narayan D.; León, Francisco; Muhammad, Ilias; Tekwani, Babu L.

doi:10.3390/molecules27134297

Cited by 32 publications

(34 citation statements)

References 210 publications

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“…In addition, some natural products from plant sources with reversible MAO inhibitory properties have been identified and are being tested in different pathological contexts. For example, some alkaloids act as potent MAO-A inhibitors and may provide beneficial effects on neuroblastoma and other cancer cell lines [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Monoamine Oxidase Inhibitors Prevent Glucose-Dependent Energy Production, Proliferation and Migration of Bladder Carcinoma Cells

Resta

Santin

Roumiguié

et al. 2022

IJMS

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Bladder cancer is the 10th most common cancer in the world and has a high risk of recurrence and metastasis. In order to sustain high energetic needs, cancer cells undergo complex metabolic adaptations, such as a switch toward aerobic glycolysis, that can be exploited therapeutically. Reactive oxygen species (ROS) act as key regulators of cancer metabolic reprogramming and tumorigenesis, but the sources of ROS remain unidentified. Monoamine oxidases (MAOs) are mitochondrial enzymes that generate H2O2 during the breakdown of catecholamines and serotonin. These enzymes are particularly important in neurological disorders, but recently, a new link between MAOs and cancer has been uncovered, involving their production of ROS. At present, the putative role of MAOs in bladder cancer has never been evaluated. We observed that human urothelial tumor explants and the bladder cancer cell line AY27 expressed both MAO-A and MAO-B isoforms. Selective inhibition of MAO-A or MAO-B limited mitochondrial ROS accumulation, cell cycle progression and proliferation of bladder cancer cells, while only MAO-A inhibition prevented cell motility. To test whether ROS contributed to MAO-induced tumorigenesis, we used a mutated form of MAO-A which was unable to produce H2O2. Adenoviral transduction of the WT MAO-A stimulated the proliferation and migration of AY27 cells while the Lys305Met MAO-A mutant was inactive. This was consistent with the fact that the antioxidant Trolox strongly impaired proliferation and cell cycle progression. Most interestingly, AY27 cells were highly dependent on glucose metabolism to sustain their growth, and MAO inhibitors potently reduced glycolysis and oxidative phosphorylation, due to pyruvate depletion. Accordingly, MAO inhibitors decreased the expression of proteins involved in glucose transport (GLUT1) and transformation (HK2). In conclusion, urothelial cancer cells are characterized by a metabolic shift toward glucose-dependent metabolism, which is important for cell growth and is under the regulation of MAO-dependent oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Monoamine Oxidase Inhibitors Prevent Glucose-Dependent Energy Production, Proliferation and Migration of Bladder Carcinoma Cells

Resta

Santin

Roumiguié

et al. 2022

IJMS

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“…Inhibiting the function of the mitochondrial complex I under the control of monoamine oxidase, MPTP is a lipophilic neurotoxin that easily crosses the blood-brain barrier and causes degenerative necrosis of DA neurons [ 29 ]. Coincidentally, curcumin inhibits monoamine oxidase B and protects DA neurons [ 17 ]. Our data showed that different doses of curcumin improved DA neuron morphology and number, mitochondrial structure, and neuronal vacuolar degeneration, with higher doses being more effective.…”

Section: Discussionmentioning

confidence: 99%

“…Curcumin, a polyphenol extracted from the rhizomes of Curcuma longa , is converted into biologically active metabolites in the intestine by microbial digestion [ 13 ]. Nowadays, it has been shown to have multiple effects such as anti-inflammatory [ 14 ], antioxidant [ 15 ], anticancer [ 16 ], and mitochondrial protection [ 17 ]. The bidirectional interplay between curcumin and gut microbes has been demonstrated, as curcumin is not only metabolized by the enzymes of the gut microbes to produce active metabolites but it also strengthens the intestinal barrier and changes the composition of the gut microbes [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Curcumin Regulates Gut Microbiota and Exerts a Neuroprotective Effect in the MPTP Model of Parkinson’s Disease

Zhu

Zhang

Hou

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objectives. The experiment aimed to explore the effects of curcumin on motor impairment, dopamine neurons, and gut microbiota in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model. Methods. Mice were randomly assigned to six groups: normal control group, solvent control group, MPTP group, curcumin-low-dose group (40 mg/kg), curcumin-medium-dose group (80 mg/kg), and curcumin-high-dose group (160 mg/kg). After 14 days, each group of mice was subjected to the pole text, the hanging test, and the open-field test. Tyrosine hydroxylase (TH) immunohistochemistry was used to observe the survival of nigrostriatal dopamine neurons. Moreover, ultrastructural changes were observed with a transmission electron microscope in mice striatal tissue cells. Then, 16S rRNA was used to assess changes in the gut microbiota. Results. (1) Each dose of curcumin reduced pole climbing time and increased suspension score and total distance moved dose-dependently. (2) All curcumin groups improved cell wrinkling and vacuolar degeneration, increased the number of TH positives, improved cell survival, and the higher the dose of curcumin, the better the effect. (3) There were differences in microbiota composition and a relative abundance among the groups. The relative abundance of Patescibacteria, Proteobacteria, and Verrucomicrobia was higher in the MPTP group. The relative abundance of Patescibacteria, Enterobacteriaceae, Enterococcaceae all decreased in all curcumin groups. In addition, the Kyoto Encyclopedia of Genes and Genomes pathways showed a reduction in the superpathway of N-acetylneuraminate degradation after medium- and high-dose curcumin administration. Conclusions. Curcumin regulates gut microbiota and exerts a neuroprotective effect in the MPTP mice model. This preliminary study demonstrates the therapeutic potential of curcumin for Parkinson’s disease, providing clues for microbially targeted therapies for Parkinson’s disease.

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“…Monoamine oxidase (MAO) and cholinesterase (ChE) play important roles in the regulation of nerve conduction by catalyzing the degradation of neurotransmitters. Along with abnormal protein aggregation, low neurotransmitter levels are associated withneuron death [ 1 , 2 , 3 ]. Alzheimer’s disease (AD) is a common neurodegenerative diseasecharacterized by low levels of the neurotransmitters acetylcholine (ACh) and butyrylcholine (BCh), both of which are involved in cognition.…”

Section: Introductionmentioning

confidence: 99%

(S)-N-Benzyl-1-phenyl-3,4-dihydroisoqunoline-2(1H)-carboxamide Derivatives, Multi-Target Inhibitors of Monoamine Oxidase and Cholinesterase: Design, Synthesis, and Biological Activity

Jin

Zhang

et al. 2023

Molecules

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A series of (S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxamide derivatives was synthesized and evaluated for inhibitory activity against monoamine oxidase (MAO)-A and-B, acetylcholine esterase (AChE), and butyrylcholine esterase (BChE). Four compounds (2i, 2p, 2t, and 2v) showed good inhibitory activity against both MAO-A and MAO-B, and two compounds (2d and 2j) showed selective inhibitory activity against MAO-A, with IC50 values of 1.38 and 2.48 µM, respectively. None of the compounds showed inhibitory activity against AChE; however, 12 compounds showed inhibitory activity against BChE. None of the active compounds showed cytotoxicity against L929cells. Molecular docking revealed several important interactions between the active analogs and amino acid residues of the protein receptors. This research paves the way for further study aimed at designing MAO and ChE inhibitors for the treatment of depression and neurodegenerative disorders.

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Natural Products Inhibitors of Monoamine Oxidases—Potential New Drug Leads for Neuroprotection, Neurological Disorders, and Neuroblastoma

Cited by 32 publications

References 210 publications

Monoamine Oxidase Inhibitors Prevent Glucose-Dependent Energy Production, Proliferation and Migration of Bladder Carcinoma Cells

Monoamine Oxidase Inhibitors Prevent Glucose-Dependent Energy Production, Proliferation and Migration of Bladder Carcinoma Cells

Curcumin Regulates Gut Microbiota and Exerts a Neuroprotective Effect in the MPTP Model of Parkinson’s Disease

(S)-N-Benzyl-1-phenyl-3,4-dihydroisoqunoline-2(1H)-carboxamide Derivatives, Multi-Target Inhibitors of Monoamine Oxidase and Cholinesterase: Design, Synthesis, and Biological Activity

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