http://informahealthcare.com/enz
ISSN: 1475-6366 (print), 1475-6374 (electronic)
J Enzyme Inhib Med Chem, Early Online: 1–5
! 2013 Informa UK Ltd. DOI: 10.3109/14756366.2013.843171
Journal of Enzyme Inhibition and Medicinal Chemistry Downloaded from informahealthcare.com by 212.252.83.146 on 10/24/13
For personal use only.
ORIGINAL ARTICLE
Total monoamine oxidase (MAO) inhibition by chestnut honey,
pollen and propolis
O. Yildiz1, F. Karahalil1, Z. Can2, H. Sahin2, and S. Kolayli2
1
Maçka Vocational High School, Karadeniz Technical University, Trabzon, Turkey and 2Department of Chemistry, Science Faculty,
Karadeniz Technical University, Trabzon, Turkey
Abstract
Keywords
Monoamine oxidase (MAO) inhibitors are generally used in the treatment of depressive
disorders and some neurodegenerative illnesses, such as Parkinson’s disease and Alzheimer’s
disease. The aim of this preliminary study was to investigate the MAO [MAO (E.C.1.4.3.4)]
inhibiting effect of various apitherapeutic products, such as chestnut honey, pollen and
propolis. Extracts’ MAO inhibition was measured using peroxidase-linked spectrophotometric
assay in enzyme isolated from rat liver microsomes, and the values are expressed as the
inhibition concentration (IC50) causing 50% inhibition of MAO. The antioxidant activity of the
bee products was also determined in terms of total phenolic content (TPC) and ferric reducing/
antioxidant power in aquatic extracts. All samples exhibited substantial inhibition of MAO,
propolis having the highest. Inhibition was related to samples’ TPCs and antioxidant capacities.
These results show that bee products possess a sedative effect and may be effective in
protecting humans against depression and similar diseases.
Honey, monoamine oxidase, pollen, propolis,
spectrophotometric peroxidase linked
assay
Introduction
Monoamine oxidase inhibitors (MAOIs) are mainly used in
psychiatry for the treatment of depressive and anxiety disorders
and in neurology for the treatment of Parkinson’s disease and
Alzheimer’s disease1–3. Honey, pollen and propolis are all natural
bee products, new therapeutic characteristics of which are
emerging every day. To date, these products have only been
known to be effective in physiological diseases, and their roles in
psychological or neurodegenerative diseases are still unknown.
Monoamine oxidases (MAOs) are a type of flavoprotein present
in the outer mitochondrial membrane of neuronal and nonneuronal cells4,5. Two isoforms have been identified, MAO-A and
MAO-B. These enzymes are responsible for the oxidative
deamination of endogenous and xenobiotic amines. They have
different substrate preference, inhibitor specificity and tissue
distributions6. Tyramine is a substrate for both MAO-A and
MAO-B.
While the classic non-selective and irreversible MAOIs, such
as phenelzine and tranylcypromine, are characterized by the risk
of inducing a hypertensive crisis when dietary tyramine is
ingested, the selective MAO-B inhibitor selegiline and the
selective and reversible inhibitor of MAO-A (RIMA) moclobemide are free from this potential interaction5,6. Alzheimer’s
disease has been linked with this mechanism, that is, increased
MAO-B activity plus reduced free radical scavenging capacity.
Parkinson’s and Alzheimer’s disease have been associated with
History
Received 22 July 2013
Revised 6 September 2013
Accepted 8 September 2013
Published online 24 October 2013
oxidative stress and increasing MAO-B activity5. MAO inhibition
is accompanied by marked changes in the sensitivity of the
organism to various dietary constituents (e.g. p-tyramine,
tryptophan and other amines and amine precursors) as well as
many drugs (e.g. sympathomimetics, opiates, reserpine and
caffeine).
Although many studies have been conducted on bee products
that have highly bioactive compounds, such as phenolic compounds, there are no studies of MAO inhibition. Previous studies to
date have assessed the antioxidant, antimicrobial, antiinflammatory, anti-carcinogenic and carbonic anhydrase (CA)
inhibitory effects and the hepatoprotective role of the bee
products2,7–16. Similarly, MAO is inhibited by some plant extracts
with a high content of phenolic compounds17–19 and some synthetic
hydrazines20. There are information gaps on MAO inhibition by
bee products, however, which this study is intended to help fill.
Materials and methods
Samples
Chestnut honey, pollen and propolis were collected from
beekeepers in the Black Sea region of northern Turkey. Samples
were stored in a refrigerator until use. Palynological identification
of the pollen and honey samples was performed using microscopic analysis. Chestnut sativa was dominant (445%) in the
pollen in the samples.
Chemicals
Address for correspondence: Oktay Yildiz, Maçka Vocational High
School, Karadeniz Technical University, Trabzon, Turkey. E-mail:
oktayyildiz29@hotmail.com
All chemicals were reagent grade and used without
further purification. Clorgyline (N-methyl-N-propargyl-3(2,4-dichlorophenoxy) propylamine hydrochloride), TroloxÕ
2
O. Yildiz et al.
(6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), pargyline (N-methyl-N-propargylbenzylamine,%97), 4-aminoantipyrine
(4-amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one,
ampyrone), p-triamine, 2,2-diphenyl-1-picrylhydrazyl (DPPH)
and horseradish peroxidase (Type VI) were purchased from
Sigma-Aldrich (St. Louis, MO). TPTZ (2,4,6-tripyridyl-s-triazine)
and Folin–Ciocalteau’s phenol reagent were obtained from Fluka
Chemie GmbH (Switzerland).
Journal of Enzyme Inhibition and Medicinal Chemistry Downloaded from informahealthcare.com by 212.252.83.146 on 10/24/13
For personal use only.
Preparations of extract of honey, pollen and propolis
samples
Aquatic honey, pollen and propolis extracts were prepared in
different concentrations. Pollen and honey samples were dissolved
easily and filtered with Whatman filter paper. The raw propolis
samples were frozen at 20 C for 24 h and ground to a fine
powder. Five grams of powder was placed in a flask (250 mL) to
which 100 mL double distilled water was added and shaken
(Heidolph Promax 2020, Schwabach, Germany) for 72 h at 45 C.
The suspension was then filtered with Whatman filter paper. The
filtrate was sonicated for 3 h using a sonicator apparatus (ElmaÕ
Transsonic Digital, Germany). Each sample was diluted to final
concentrations and was kept at 20 C until use.
Determination of total antioxidant capacity
Total antioxidant capacities of the bee products were measured
using the total phenolic contents (TPC) and ferric reducing/
antioxidant power (FRAP) methods. TPCs of the aquatic extracts
were determined using Folin–Ciocalteu assay21 with slight
modifications22. Different concentrations of aqueous sample
extracts were diluted. Gallic acid was used as the reference
standard compound, and the results were expressed as milligrams
gallic acid per gram sample. Subsequently, 680 mL distilled water,
20 mL aquatic extracts and 400 mL of 0.2 N Folin–Ciocalteu
reagents were mixed in a tube and then vortexed. After 2 min,
400 mL Na2CO3 (7.5%) was added and incubated for 2 h at room
temperature. Absorbance was measured at 760 nm at the end of
the incubation period. The concentration of TPCs was calculated
as milligrams of gallic acid equivalents of gram samples using a
calibration curve. All measurements were performed in triplicate.
The reducing power ability of ferric tripyridyltriazine
(Fe-III-TPTZ) complex from the sample aquatic extracts was
measured using the methods described by Benzie and Strain23
with some modifications. The test involved the reduction of ferric
tripyridyltriazine (Fe-III-TPTZ) complex to a blue-colored Fe (II)
TPTZ by samples’ antioxidant agents. Working FRAP reagent
was prepared as required by mixing 25 mL of 300 mM acetate
buffer, pH 3.6, with 2.5 mL of 10 mM TPTZ solution in 40 mM
HCl and 2.5 mL of 20 mM FeCl36H2O solution. Subsequently, 3
mL freshly prepared FRAP reagent and 100 mL of the samples
were mixed and incubated in 4 min at 37 C. Absorbance was read
at 595 nm against a reagent blank containing distilled water. For
comparative purposes, TroloxÕ was also tested under the same
conditions as a standard antioxidant compound23. FRAP values
were expressed as millimoles of Trolox per gram of sample.
Isolation of mitochondria from rat liver
MAO was gradually purified from rat liver mitochondria by
partial modification of the method described by Holt et al.24. The
animals were decapitated. The livers were immediately excised,
placed in KCl (1.15%) and stored at 20 C until use. After
dissolution, the liver was decanted, washed in potassium phosphate buffer (0.2 M, pH 7.6) and homogenized 1:40 (w/v) in 0.3 M
sucrose at 15 000/min using a homogenizator (Ika-Werke, Ultra
TurraxÕ T25 Basic, Germany). Homogenate was centrifuged at
J Enzyme Inhib Med Chem, Early Online: 1–5
3000 rpm for 12 min. Obtained supernatant was re-centrifuged at
9450 rpm for 30 min and collapsed crude mitochondrial pellet.
After the crude mitochondrial pellet was resuspended in 5 mL of
0.3 M sucrose, mitochondria were separated with density gradient
centrifugation. The suspension was slowly layered onto 40 mL of
1.2 M sucrose and centrifuged at 21 753 rpm for 2 h and then
decanted. Mitochondria obtained were suspended in 15 mL
potassium phosphate buffer. Prepared mitochondria suspension
was analyzed immediately because homogenates lose their
activity in 24 h. In our preliminary experiments, homogenates
exhibited a decline in activity in one day.
Measurement of inhibition
Activity measurements were performed using photometric assay.
Enzyme inhibition was measured using the method described by
Holt et al.24 and Schmidt et al.25 with minor modifications.
Samples were serially diluted with distilled water, and 40 mL of
each dilution was placed in 96-well microplates (PS Microplate,
non-sterile, Greiner Bio-One, Germany) to give final concentrations from 5 to 0.00005 mg/mL (five dilutions for samples).
Subsequently, 40 mL of water-diluted samples was placed in 96well microplates to give final concentrations from 5 to
0.00065 mg/mL (at least five dilutions). Each test well contained
120 mL amino substrate solution (2.5 mM p-tyramine in potassium
phosphate buffer), 40 mL chromogenic solution (1 mM vanillic
acid, 0.5 mM 4-aminoantipyrine, 4 U/mL peroxidase in potassium
phosphate buffer), 40 mL enzyme mixture obtained from rat liver
homogenates and 40 mL of the bee sample extract. Chromogenic
solutions were prepared daily and kept at 4 C until use. Distilled
water was used as a negative control. Background wells contained
potassium phosphate buffer (0.2 M, pH 7.6) in place of the
enzyme mixture. Reactions were observed at 490 nm using a
microplate reader (Chromate 4300). Plates were incubated
between readings at 37 C. Absorbance readings were taken
every 3 min over a period of 42 min.
Statistical analysis
The results were presented as mean values standard deviations
of triplicate measurements. Data were tested using analysis of
variance (ANOVA) with SPSS software (version 9.0 for Windows
98, SPSS Inc., Chicago, IL). The means statistically different
from each other were compared using Duncan’s multiple
comparison.
Result and discussion
This study investigated the inhibitory effect on MAO enzyme of
aquatic extracts obtained from bee products (honey, pollen and
propolis). Before inhibition was investigated, TPC levels and total
antioxidant capacities of all three bee products were determined.
The results obtained are shown in Table 1. TPC and FRAP
activities in the aquatic extracts investigated were determined in
the following descending order – propolis, pollen and honey.
Propolis was the bee product with the highest antioxidant activity.
Table 1. Total phenolic contents (TPC) and ferric reducing/antioxidant
power (FRAP) of aqueous extracts.
Samples
Chestnut honey
Pollen
Propolis
Total phenolic content
(mg GAE/g sample)
FRAP mM
Trolox/g samples
0.98 0.03*
52.12 2.14y
89.51 0.17z
24.11 1.10*
124.62 4.88y
509.86 12.11z
*,y,zThe results of the values are significantly different (p50.05) from
each other.
Total MAO inhibition
Bee product phenolic compounds vary depending on the
geographic characteristics and the plant flora of the region
where they are collected. However, the TPC and FRAP values for
the three bee products in this study did not exhibit similar results
compared with other studies in the literature. Tezcan et al.26
reported that the TPC of chestnut honey ranged between
0.95 mg/g and 1.13 mg/g. Similarly, another study reported
aquatic pollen sample TPCs15 of 56.60 mg/g. Studies showing
the antioxidant property of propolis have reported that ethanolic
propolis extracts have higher phenolic content levels and exhibit
greater antioxidant activity in association with this16,27. Recently,
however, aquatic propolis extracts have been reported to contain
significant amounts of phenolic content. Gülçin et al.28 reported
aquatic propolis extract TPC of 124 mg GAE/g. Sahin et al.15
reported TPC levels of 13.45 mg/g in aquatic propolis samples.
y = 0,0274ln(x) + 0,2777
0.35
y = 0,0564ln(x) + 0,1055
0.3
Total MAO acvity
y = 0,0564ln(x) + 0,083
y = 0,0569ln(x) + 0,0888
0.25
y = 0,0565ln(x) + 0,0942
0.2
y = 0,0537ln(x) + 0,0913
Honey concentraon -1
0.15
Honey concentraon -2
Honey concentraon -3
0.1
Honey concentraon -4
Honey concentraon -5
0.05
Honey concentraon -6
0
0
10
20
30
40
50
Time(min.)
0.4
Figure 2. Total MAO inhibition by different
concentrations of pollen.
y = 0,017ln(x) + 0,296
0.35
y = 0.0289ln(x) + 0.1837
y = 0.0284ln(x) + 0.143
0.3
y = 0.0351ln(x) + 0.1377
0.25
y = 0.0286ln(x) + 0.1359
Pollen concentraon -1
0.2
Pollen concentraon -2
0.15
Pollen concentraon -3
Pollen concentraon -4
0.1
Pollen concentraon -5
Pollen concentraon -6
0.05
0
0
10
3
More phenolic material appears to pass into the aquatic environment with the extraction technique we used (89.51 mg GAE/g
propolis).
MAO activities detected by photometric assay were plotted
over 42 min (Figures 1–3). The total MAO activity curve was
showed sigmoidal curve. This shows that the enzyme activity
increases logarithmically. When honey, pollen and propolis were
added to the enzyme environment, enzyme activity decreased
significantly; in other words, all three natural products inhibited
MAO (Figures 1–3). Figures 1–3 show that inhibition rose
significantly with increasing concentrations of honey, pollen and
propolis. IC50 values were calculated in order to show total MAO
enzyme inhibition values in a concrete form. IC50 value is defined
as the level that inhibits 50% of the enzyme, and the values
obtained are shown in Table 2. A low IC50 shows a high enzyme
0.4
Figure 1. Total MAO inhibition by different
concentrations of honey.
Total MAO acvity
Journal of Enzyme Inhibition and Medicinal Chemistry Downloaded from informahealthcare.com by 212.252.83.146 on 10/24/13
For personal use only.
DOI: 10.3109/14756366.2013.843171
20
30
Time(min.)
40
50
4
O. Yildiz et al.
J Enzyme Inhib Med Chem, Early Online: 1–5
0.4
Figure 3. Total MAO inhibition by different
concentrations of propolis.
y = 0.0176ln(x) + 0.2969
y = 0.0117ln(x) + 0.2005
0.35
y = 0.0091ln(x) + 0.198
y = 0.0137ln(x) + 0.17
0.3
Total MAO acvity
Journal of Enzyme Inhibition and Medicinal Chemistry Downloaded from informahealthcare.com by 212.252.83.146 on 10/24/13
For personal use only.
y = 0.0149ln(x) + 0.159
0.25
y = 0.0147ln(x) + 0.1477
0.2
0.15
Propolis concentraon -1
Propolis concentraon -2
0.1
Propolis concentraon -3
0.05
Propolis concentraon -4
Propolis concentraon -5
0
0
10
20
30
40
50
Propolis concentraon -6
Time (min.)
Table 2. Inhibitor effects of aquatic bee products on
total Mono amine oxidase (MAO).
Samples
IC50 (mg/mL)
Chestnut honey
Pollen
Propolis
41.60 6.05*
30.56 4.02y
24.95 3.75z
*,y,zThe results of the values are significantly
different (p50.05) from each other.
inhibition capacity. Propolis, pollen and honey, in decreasing
order, all inhibited MAO enzyme activity (Table 2). We attribute
propolis exhibiting higher MAO inhibition than pollen and honey
to phenolic substances being present in greater amounts in its
composition. In a previously study17 IC50 values of Clorgyline
(selective MAO-A inhibitor) and Selegiline (selective MAO-B
inhibitor) were found as 31 10 nM and 111 86 nM, respectively. Many researchers have reported a positive correlation
between TPC and biological activities such as antioxidant,
antimicrobial and anti-inflammatory effects in natural samples,
as well as in bee products27,29,30. Similarly in this study, propolis
had higher phenolic contents than the other bee products, and
exhibited greater biological activity as a result.
Stafford et al.17 studied MAO inhibition by various southern
African traditional medicinal plants and reported that ethyl
acetate extracts of Ruta graveolens exhibited the best MAO
inhibitory activity (IC50: 5 1 mg/mL). Alper et al.31 suggested
that the inhibition of MAO activity may attenuate the process of
aging by reducing increased lipid peroxidation and concomitant
oxidant stress. Some studies on MAO inhibition were conducted
using alcoholic extracts, although aquatic extracts were also
effective in our study. Propolis, pollen and honey have been used
in different treatments in apitherapy. This study suggests that
these apitherapeutic products may also have a role in the treatment
of depressive disorders and some neurodegenerative illnesses. In
the light of this study, more extensive and detailed studies on
specific MAO-A and MAO-B inhibition activity are now needed.
Extracts of Ginkgo biloba (EGb761Õ ) have been reported to
enhance dopaminergic neurotransmission in animal models32.
However, Jäger et al.33 studied 17 different Danish folk medicine
plants extracts and reported that some of the plant extracts
(Borago officinalis L. and Arnica montana L.) exhibited significant inhibitory effects on MAO–A. It is very difficult to account
for the inhibition mechanism, but both studies showed that the
plants contain highly bioactive compounds, such as alkaloids,
phenols, flavonoids, chalcones and coumarins, suggesting that
these may responsible for the inhibitory effects on MAO33.
Declaration of interest
This study was supported by Research Fund of Karadeniz Technical
University (Project No: KTU-BAP 02-1159). The authors have declared
no conflicts of interest with the presented data from this article.
References
1. Laux G, Classen W, Sofic E, et al. Clinical, biochemical and
psychometric findings with the new MAO-A-inhibitors moclobemide and brofaromine in patients with major depressive disorder.
J Neural Transm 1990;32:189–95.
2. LeBlanc BW, Davis OK, Boue S, et al. Antioxidant activity of
Sonoran Desert bee polen. Food Chem 2009;115:1299–305.
3. Li X-M, Juorio AV, Boulton AA. Some new mechanisms underlying
the actions of deprenyl: possible relevance to neurodegeneration.
Prog Brain Res 1995;106:99–112.
4. Greenawalt JW. Localization of monoamine oxidase in rat liver.
Adv Biochem Psychopharmacol 1972;5:207–26.
5. Volz HP, Gleiter CH. Monoamine oxidase inhibitors. A perspective
on their use in the elderly. Drugs Aging 1998;13:341–55.
6. Yamada M, Yasuhara H. Clinical pharmacology of MAO inhibitors:
safety and future. Neurotoxicology 2004;25:215–21.
7. Al-Mamary MA, Al-Meeri A, Al-Habori M. Antioxidant activities
and total phenolics of different types of honey. Nutr Res 2002;22:
1041–7.
8. Özcan M, Ceylan A, Ünver A, Yetişir R. Antifungal effect of pollen
and propolis extracts colleceted from different regions of Turkey.
Uludağ Arıcılık Dergisi 2003;3:33–6.
Journal of Enzyme Inhibition and Medicinal Chemistry Downloaded from informahealthcare.com by 212.252.83.146 on 10/24/13
For personal use only.
DOI: 10.3109/14756366.2013.843171
9. Russo A, Cardile V, Sanchez F, et al. Chilean propolis: antioxidant
activity and antiproliferative action in human tumor cell lines.
Life Sci 2004;76:545–58.
10. Almeida-Muradian LB, Pamplona LC, Coımbra S, Barth OM.
Chemical composition and botanical evaluation of dried bee pollen
pellets. J Food Compos Anal 2005;18:105-111.
11. Nasuti C, Gabbianelli R, Falcioni G, Cantalamessa F. Antioxidative
and gastroprotective activities of anti-inflammatory formulations
derived from chestnut honey in rats. Nutr Res 2006;26:130–7.
12. Almaraz-Abarca N, Campos MG, Ávila-Reyes JA, et al. Antioxidant
activity of polyphenolic extract of monofloral honeybee-collected
pollen from mesquite (Prosopis juliflora, Leguminosae). J Food
Compos Anal 2007;20:119–24.
13. Medeiros KCP, Figueiredo CAV, Figueredo TB, et al. Anti-allergic
effect of bee pollen phenolic extract and myricetin in ovalbuminsensitized mice. J Ethnopharmacol 2008;119:41–6.
14. Moreira L, Dias LG, Pereira JA, Estevinho L. Antioxidant properties, total phenols and pollen analysis of propolis samples from
Portugal. Food Chem Toxicol 2008;46:3482–5.
15. (a) Kücük M, Kolayli S, Karaoglu Ş, et al. Biological activities and
chemical composition of three honeys of different types from
Anatolia. Food Chem 2007;100:526–34. (b) Sahin H, Aliyazicioglu
R, Yildiz O, et al. Honey, polen, and propolis extracts show potent
inhibitory activity against the zinc metalloenzyme carbonic
anhydrase. J Enzym Inhib Med Chem 2011;26:440–4.
16. Sahin H, Can Z, Yıldız O, et al. Inhibition of carbonic anhydrase
isozymes I and II with natural products extracted from plants,
mushrooms and honey. J Enzym Inhib Med Chem 2012;27:395–402.
17. Stafford GI, Pedersen PD, Jäger AK, Van Staden J. Monoamine
oxidase inhibition by southern African traditional medicinal plants.
S Afr J Bot 2007;73:384–90.
18. Kelekçi NK, Yabanoğlu S, Küpeli E, et al. A new therapeutic
approach in Alzheimer disease: some novel pyrazole derivatives as
dual MAO-B inhibitors and antiinflammatory analgesics. Bioorgan
Med Chem 2007;15:5775–86.
19. Mu LH, Wang B, Ren HY, et al. Synthesis and inhibitory effect of
piperine derivates on monoamine oxidase. Bioorgan Med Chem
Letter 2012;22:3343–8.
20. Dar A, Khan KM, Ateeq HS, et al. Inhibition of monoamine
oxidase-A activity in rat brain by synthetic hydrazines: structure –
activity relationship (SAR). J Enzyme Inhib Med Chem 2005;20:
269–74.
View publication stats
Total MAO inhibition
5
21. Slinkard K, Singleton VL. Total phenol analysis: automation and
comparison with manual methods. Am J Enol Viticult 1977;28:
49–55.
22. Yıldız O, Alpaslan M. Properties of Rosehip Marmalades. Food
Technol Biotechnol 2012;50:98–106.
23. Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as
a measure of antioxidant power: the FRAP assay. Anal Biochem
1996;239:70–6.
24. Holt A, Sharman DS, Baker GB, Palcic MM. A continuous
spectrophotometric assay for monoamine oxidase and
related enzymes in tissue homogenates. Anal Biochem 1997;244:
384–92.
25. Schmidt K, Li Z, Schubert B, et al. Screening of entomopathogenic
Deuteromycetes for activities on targets involved in degenerative
diseases of the central nervous system. J Ethnopharmacol 2003;89:
251–60.
26. Tezcan F, Kolaylı S, Sahin H, et al. Evaluation of organic acid,
sacchraride composition and antioxidant properties of some authentic Turkish honeys. J Food Nutr Res 2011;50:33–40.
27. Aliyazıcioglu R, Şahin H, Erturk O, et al. Properties of phenolic
composition and biological activity of propolis from Turkey. Int J
Food Prop 2013;16:277–87.
_ Bursal E, Şehitoğlu MH, et al. Polyphenol contents and
28. Gülcin I,
antioxidant activity of lyophilized aqueous extract of propolis from
Erzurum, Turkey. Food Chem Toxicol 2010;48:2227–38.
29. Ahn MR, Kumazawa S, Usui Y, et al. Antioxidant activity
and constituents of propolis collected in various areas of China.
Food Chem 2007;101:1383–92.
30. Gregoris E, Stevanato R. Correlations between polyphenolic composition and antioxidant activity of Venetian propolis. Food Chem
Toxicol 2010;48:76–82.
31. Alper G, Özgönül M, Sağin F, et al. The effect of a monoamine
oxidase (MAO)-B inhibitor; pargyline on oxidant stress/antioxidant
status in aging rat tissues. Ege Tıp Dergisi 2007;46:27–32.
32. Fehske CJ, Leuner K, Muller WE. Ginkgo biloba extract (EGb761)
influences monoaminergic neurotransmission via inhibition of NE
uptake, but not MAO activity after chronic treatment. Pharmacol
Res 2009;60:68–73.
33. Jäger AK, Gauguin B, Andersen J, et al. Screening of plants used in
Danish folk medicine to treat depression and anxiety for affinity to
the serotonin transporter and inhibition of MAO-A.
J Ethnopharmacol 2013;145:822–5.