Identification of Kaempferol as a Monoamine Oxidase Inhibitor and Potential Neuroprotectant in Extracts of <i>Ginkgo Biloba</i> Leaves

Sloley, B.D.; Urichuk, Liana; Morley, Paul; Durkin, Jon P.; Shan, Jie; Pang, Peter K.T.; Coutts, Ronald T.

doi:10.1211/0022357001774075

Cited by 154 publications

(71 citation statements)

References 28 publications

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“…Because benzoflavanones have not previously been reported to act on MAOA as inhibitors, [28][29][30] and the inhibitory effect of one of benzoflavones, 3-(4-methoxyphenyl)-2,3-dihydro-1H-benzo[ f ] chromen-1-one used in this study is comparable to that of clorgyline which is known as MAOA inhibitor, 31 our findings are meaningful.…”

supporting

confidence: 51%

Discovery of Monoamine Oxidase A Inhibitors Derived from in silico Docking

Jo¹,

Sung²,

Lee³

et al. 2012

Bulletin of the Korean Chemical Society

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Although more than 20,000 papers concerning monoamine oxidase (MAO) have been reported in PubMed since the 1950s, over 300 papers are still being published every year on this topic. This indicates the importance of MAO, which was discovered by Mary Hare-Bernheim in 1928. 1Two isoforms of MAO have been identified based on the selectivity to their substrates and inhibitors; they are called MAOA and MAOB. While the former shows a high affinity for serotonin and norepinephrine, the latter has a high affinity for β-phenylethylamine. Likewise, MAOA is selectively inhibited by clorgyline and MAOB by selegiline. 2MAOA and MAOB are encoded from different genes that are located in the human X chromosome.3 They are activated by different transcription factors; 4 thus, the expressions of the two proteins are localized: the ratio of MAOA to MAOB is 1:3 in the human brain, 1:1 in the liver, and 4:1 in the intestine.5,6 MAO acts on monoamines, but it does not metabolize diamines. It metabolizes monoamine to aldehyde, which is then oxidized to carboxylic acid by aldehyde dehydrogenase. During this oxidation, MAO requires flavin adenine dinucleotide (FAD), which becomes FADH 2 . The oxidation of FADH 2 is achieved by the production of hydrogen peroxide from oxygen and protons. Consequently, catabolism of MAO produces hydrogen peroxide. Especially, MAOA oxidizes and degrades serotonin which modulates neuropsychiatric function and dysfunction. 7,8 In addition, MAOA has effects on several psychiatric conditions such as anxiety, mood, and impulsivity, and is implicated in several psychiatric illnesses and elevated in depressive disorder. 9,10

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supporting

confidence: 51%

Discovery of Monoamine Oxidase A Inhibitors Derived from in silico Docking

Jo¹,

Sung²,

Lee³

et al. 2012

Bulletin of the Korean Chemical Society

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“…, and demonstrated anti-depressant actions in mice 40 . It is not clear how Maca acts on reducing psychological symptoms, although flavonoids present in Maca may be responsible for these actions [40][41][42][43] . Interestingly, the reduced psychological symptoms (depression and anxiety) did not correlate with reduced vasomotor symptoms (hot flushes), despite a strong association between the two 44,45 .…”

Section: Discussionmentioning

confidence: 99%

Maca reduces blood pressure and depression, in a pilot study in postmenopausal women

et al. 2014

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Objective: Lepidium meyenii (Maca), a herbaceous plant, has been used for centuries for its fertility enhancing and aphrodisiac properties. In an Australian study, Maca improved anxiety and depressive scores. The effects of Maca on hormones, lipids, glucose, serum cytokines, blood pressure, menopausal symptoms and general well-being in Chinese postmenopausal women were evaluated Methods: A randomized, double-blind, placebo-controlled crossover study was conducted in 29 postmenopausal Hong Kong Chinese women. They received 3.3 g/day of Maca or placebo for 6 weeks each, in either order, over 12 weeks. At baseline, week 6 and week 12, estradiol, follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG), thyroid stimulating hormone (TSH), full lipid profiles, glucose and serum cytokines, were measured. The Greene Climacteric, SF-36v2, Women's Health Questionnaire and Utian quality of life, scales were used to assess the severity of menopausal symptoms and health related quality of life.Results: There were no differences in estradiol, FSH, TSH, SHBG, glucose, lipid profiles and serum cytokines amongst those who received Maca as compared to placebo group, however, a significant decrease in both systolic and diastolic blood pressure was apparent after Maca treatment. The Greene Climacteric Scale revealed lower scores in the areas of psychological symptoms, including anxiety and depression following Maca. SF-36v2 showed stronger improvement in general and mental health when compared to baseline, whilst the women's health questionnaire showed improvement in depression and anxiety symptoms following Maca consumption. The Utian quality of life scoring did not show any differences in all domains tested.Conclusions: Maca does not exert hormonal or immune biological action in the small cohort of patients studies, however, it appears to reduce symptoms of depression and improve diastolic blood pressure in Chinese postmenopausal women. Although results are comparable to previous similar published studies in postmenopausal women, there might be a cultural difference among the Chinese postmenopausal women in terms of symptom reporting.

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“…39) It also has been shown that the MAO-B activity is elevated with age, which is directly related to PD, and MAO-B inhibitor has been used as a classic drug for clinical treatment. In the PD mouse model, MPTP was metabolized selectively by MAO-B to the active toxin MPP ϩ .…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effect of Kaempferol against a 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Mouse Model of Parkinson's Disease

Shen

2011

Biological & Pharmaceutical Bulletin

133

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Parkinson's disease (PD) is a progressive, age-related, neurodegenerative disorder characterized by bradykinesia, rigidity, resting tremor and gait disturbance 1) ; it occurs in 1-2% of the population over the age of 60 years.2) Typical neuropathologic features of the disease are dopaminergic neuron degeneration in the substantia nigra and the presence of eosinophilic intracytoplasmic inclusions (Lewy bodies) in the residual dopaminergic neurons. The most widely used mouse model of PD is produced by systemically administering the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).3) MPTP is converted by monoamine oxidase B (MAO-B) to 1-methyl-4-phenylpyridinium (MPP ϩ ), which is a neurotoxic metabolite and could block cellular respiration, promote reactive oxygen species (ROS) formation, and cause neuronal death. 4,5) Oxidative stress has been implicated either as the cause or as a consequence of the pathogenetic mechanisms responsible for neurodegenerative disease, including PD. Indeed, the brain is prone to producing ROS and oxidative stress, due to its high metabolic rate, combined with the high content of oxidizable molecules, such as dopamine and neuromelanin, whose metabolism generates ROS. [6][7][8] Superoxide dismutase (SOD) is one of the key enzymes that provide the first line of defense against pro-oxidants. Glutathione peroxidase (GSH-PX) is thought to play an important role in protecting membranes from damage due to lipid peroxidation. The major detoxification function of GSH-PX is the termination of radical chain propagation by quick reduction to yield further radicals.9) The levels of SOD and GSH-PX activity reflect the ability of organism to eliminate free radicals. Malondialdehyde (MDA) is the end product of lipid peroxidation, and its level could indirectly reflect the metabolic degree of oxygen radicals, thus serving as an index of oxidative damage. 10)Kaempferol is a prototype member of the flavonol subclass of flavonoids, which is widely found in tea, broccoli, grapefruit, brussel sprouts and apple and is claimed to have strong antioxidant and anti-inflammatory properties. 11)Kaempferol, can be given orally, is absorbed well and the bioavailability is proportionate to its dose.12) Kaempferol had earlier been shown to afford efficient neuroprotection against several apoptosis and necrosis-inducing insults, such as oxidized low-density lipoproteins 13,14) and L-glutamate. 15,16)Ishige et al. 15) demonstrated that kaempferol efficiently blocked the increase in ROS associated with the oxidative stress caused by glutamate in the mouse hippocampal cell line demonstrated that kaempferol exerted a strong and prolonged protective effect against rotenone toxicity, which was a classical toxin inducing PD. Striatal glutamatergic response of rat brain slices was also preserved by kaempferol, posing a more general protection of kaempferol in PD.Preliminary studies in our laboratory have shown that kaempferol derivatives prevent oxidative stress-induced cell death in a DJ-1-dependent manner in...

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Identification of Kaempferol as a Monoamine Oxidase Inhibitor and Potential Neuroprotectant in Extracts of Ginkgo Biloba Leaves

Cited by 154 publications

References 28 publications

Discovery of Monoamine Oxidase A Inhibitors Derived from in silico Docking

Discovery of Monoamine Oxidase A Inhibitors Derived from in silico Docking

Maca reduces blood pressure and depression, in a pilot study in postmenopausal women

Neuroprotective Effect of Kaempferol against a 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Mouse Model of Parkinson's Disease

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