- Access to this full-text is provided by Hindawi.
- Learn more
Download available
Content available from Evidence-based Complementary and Alternative Medicine
This content is subject to copyright. Terms and conditions apply.
Research Article
Antidepressant-Like and Antioxidant Effects of
Plinia trunciflora in Mice
Cassia Sacchet,1Ricieri Mocelin,1Adrieli Sachett,2Fernanda Bevilaqua,2Rafael Chitolina,2
Fernanda Kuhn,1Aline Augusti Boligon,3Margareth Linde Athayde,3
Walter Antonio Roman Junior,2Denis Broock Rosemberg,1,4 Jacir Dal Magro,1
Greicy Michelle Marafiga Conterato,1,5 andAngeloL.Piato
1,6
1Programa de P´
os-Graduac¸˜
ao em Ciˆ
encias Ambientais, Unochapec´
o, Avenida Senador Att´
ılio Fontana 591E,
89809-000 Chapec´
o, SC, Brazil
2N´
ucleo de Fitoter´
apicos,ProgramadeP
´
os-Graduac¸˜
ao em Ciˆ
encias da Sa´
ude, Unochapec´
o, Avenida Senador Att´
ılio Fontana 591E,
89809-000 Chapec´
o, SC, Brazil
3Laborat´
orio de Fitoqu´
ımica, Universidade Federal de Santa Maria, Avenida Roraima 1000, 97105-900 Santa Maria, RS, Brazil
4Programa de P´
os-Graduac¸˜
ao em Bioqu´
ımica Toxicol´
ogica, Universidade Federal de Santa Maria, Avenida Roraima 1000,
97105-900 Santa Maria, RS, Brazil
5Laborat´
orio de Fisiologia da Reproduc¸˜
aoAnimal,UniversidadeFederaldeSantaCatarina,RodoviaUlissesGaboardi,Km3,
Campus Curitibanos, 89520-000 Curitibanos, SC, Brazil
6Programa de P´
os-Graduac¸˜
ao em Farmacologia e Terapˆ
eutica, Universidade Federal do Rio Grande do Sul,
Avenida Sarmento Leite 500/305, 90050-170 Porto Alegre, RS, Brazil
Correspondence should be addressed to Angelo L. Piato; angelopiato@gmail.com
Received March ; Revised June ; Accepted June
Academic Editor: Menaka C. ounaojam
Copyright © Cassia Sacchet et al. is is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
e jaboticaba tree, Plinia trunciora (O. Berg) Kausel, is popularly named “jabuticabeira” in Brazil and is used in folk medicine to
treat diabetes and chronic inammation of the tonsils, but studies evaluating the central eects of this species are limited. is study
evaluated the antidepressant-like and antioxidant eects of P. t r u n c i o r a (PT) aqueous extract, in which ve dierent anthocyanins
were identied. PT showed signicant ferric-reduction power and DPPH radical scavenging activity in vitro and reduced lipid
peroxidation both in vitro and ex vivo. At the behavioural level, PT ( and mg/kg, i.p.) dose-dependently reduced immobility
time in the tail suspension test in Swiss male mice. e identication of bioactive compounds accompanied by the in vitro and ex
vivo antioxidant activity of PT suggests that these activities might be related to the antidepressant-like activity of P. t r u n c i o r a .
1. Introduction
Depression is a common, serious, and recurrent chronic
affective disorder characterized by anhedonia, headache,
sleep disturbances, changes in sexual desire, and a loss of
energy []. is disease is among the ve most prevalent in
theworldandisexpectedtobethesecondleadingcause
of disability in []. e monoaminergic hypothesis
of depression [] does not provide a full understanding of
the progression, causes, and pharmacotherapy of depression.
New hypotheses have been postulated, and oxidative stress
has been suggested to be involved in the pathophysiology of
depression [].
Oxidative stress is a condition in which an imbalance
between the production of free radicals and endogenous
antioxidant defenses occurs [], culminating in decreased cell
antioxidant capacity. e superoxide anion (O2∙−)andhydro-
gen peroxide (H2O2) produced during respiratory chain may
generate the highly deleterious hydroxyl radical (∙OH) via
the Fenton reaction []. e overproduction of these species
is related to protein, DNA, and lipid oxidation []aswell
as the inactivation of important antioxidant enzymes, such
Hindawi Publishing Corporation
Evidence-Based Complementary and Alternative Medicine
Volume 2015, Article ID 601503, 9 pages
http://dx.doi.org/10.1155/2015/601503
Evidence-Based Complementary and Alternative Medicine
as catalase (CAT), superoxide dismutase (SOD), glutathione
peroxidase (GPx), and thioredoxin reductase (TrxR) [].
e overproduction of ROS and oxidative stress have been
implicated in the pathophysiological processes related to
various diseases, including Alzheimer’s, Parkinson’s, anx-
iety, and depression [–]. In this sense, plants emerge
as potential alternatives for the treatment of oxidative
stress-related diseases, considering that they are important
sources of carotenoids, avonoids, vitamins, and polyphe-
nols.
e Myrtaceae family consists of , species distributed
in genera whose occurrence has been described in
subtropical and tropical regions of the world, mainly Cen-
tral and South America and Australia []. e jaboticaba
tree, Plinia trunciora (O. Berg) Kausel, a synonym of
Myrciaria trunciora O. Berg, Eugenia cauliora O. Berg,
and Myrciaria peruviana (Poir.)Mattosispopularlynamed
“jabuticabeira” in Brazil (source: http://www.tropicos.org/).
In folk medicine, species of Plinia have been used to treat
various diseases, such as diabetes and chronic inammation
of the tonsils []. However, studies that evaluate the eects of
this species on the central nervous system (CNS) are scarce in
the literature. erefore, the aim of this study was to evaluate
the antidepressant-like eect of P. t r u n c i o r a aqueous extract
in the tail suspension test. e identication of bioactive
compounds and the in vitro and ex vivo antioxidant eects
of P. t r u n c i o r a were investigated in order to establish if the
antidepressant-like eect of this plant could be related to
these properties.
2. Materials and Methods
2.1. Plant Material. e whole fruits of Plinia trunciora
werecollectedinAlpestre(RS,Brazil)(
∘.Sand
∘.O), in September, and taxonomically identied by
Marcos Eduardo Guerra Sobral (botanical), where a voucher
has been deposited in the university herbarium (number
).
2.2. Preparation of Aqueous Extract of P. trunciora (PT).
e aqueous extracts of whole fruits were prepared based
on the methodology described by Kuskoski et al. []. e
whole fruit ( g) of P. t r u n c i o r a was mixed with mL
of distilled water and acidied with concentrated HCl until
pH .. Aer trituration for min, the solution was cooled to
∘C over h to extract the anthocyanins. e solution was
then centrifuged, and the supernatant was frozen and further
lyophilized. Prior to the in vitro and ex vivo experiments, the
lyophilized material was dissolved in ultrapure water (Milli-
Q) at the desired concentrations or doses.
2.3. Total Phenolic Compounds (TPC). e total phenolic
compounds (TPC) in the PT were determined according to
the method described by Singleton and Rossi [], which
is based on the reduction of the phosphowolframate phos-
phomolybdate complex by phenolics to a blue product that
is measured at nm. e results are expressed as gallic
acid equivalents (mg gallic acid equivalents/g fresh fruit),
andthevaluesarepresentedasthemeansoftriplicateanaly-
sis.
2.4. Total Monomeric Anthocyanins (TMA). e total mon-
omeric anthocyanin (TMA) content was determined using
the pH dierential method []. e anthocyanin con-
tent was calculated using the molar absorptivity (𝜀)and
molecular weights (MW) of cyanidin -O-glucoside (𝜀=
, L/mol⋅cm; MW = . g/mol). e results are ex-
pressed as mg of cyanidin -O-glucoside equivalents/ g
fresh fruit.
2.5. Identication and Quantication of Anthocyanins in PT
2.5.1. Chemical, Apparatus, and General Procedures. All
chemicals were of analytical grade. Acetonitrile and formic
acid were purchased from Merck (Darmstadt, Germany).
Cyanidin chloride, malvidin chloride, cyanidin -O-gluco-
side chloride, malvidin -O-glucoside chloride, and delphini-
din -O-glucoside chloride were acquired from ChromaDex.
High performance liquid chromatography (HPLC-DAD) was
performed with a Shimadzu Prominence Auto Sampler (SIL-
A) HPLC system (Shimadzu, Kyoto, Japan) equipped with
Shimadzu LC-AT reciprocating pumps connected to a
DGU A degasser with a CBM A integrator, SPD-MA
diode array detector, and LC solution . SP soware.
2.5.2. Quantication of Compounds by HPLC-DAD. Reverse
phase chromatographic analyses were carried out under
gradient conditions using a C column (. mm × mm)
packed with 𝜇m diameter particles; the mobile phase was
water containing % formic acid (A) and acetonitrile (B),
and the composition gradient was % of B until min
and changed to obtain %, %, %, %, %, %, and
%Bat,,,,,,andmin,respectively
[]. e P. t r u n c i o r a aqueousextractandmobilephase
were ltered through a . 𝜇m membrane lter (Millipore)
andthendegassedinanultrasonicbathpriortouse;the
aqueous extract was analyzed at a concentration of mg/mL.
e ow rate was . mL/min, the injection volume was
𝜇L, and the wavelength was nm. Stock solutions of
standards references were prepared in the HPLC mobile
phase at a concentration range of . to . mg/mL.
e chromatography peaks were conrmed by comparing
their retention times with those of the reference standards
and DAD spectra ( to nm). All chromatography
operations were carried out at ambient temperature and in
triplicate [].
2.6. Antioxidant Activity In Vitro
2.6.1. Determination of Ferric Reducing Antioxidant Power
(FRAP). e FRAP assay was based on Benzie and Strain
[], by measuring the absorbance of the complex formed
between Fe2+ and Ferric-,,-tripyridyl-s-triazine (TPTZ)
at nm aer incubation (∘C/ min) with PT (–
𝜇g/mL).eincreaseintheabsorbancewascompared
to that induced by ascorbic acid (standard), and the results
Evidence-Based Complementary and Alternative Medicine
areexpressedasthemeansoftheabsorbanceoftriplicate
experiments (𝑛=3).
2.6.2. 1,1-Diphenyl-2-2-picrylhydrazyl Radical Scavenging
Assay. e antiradical powers of the dierent concentrations
of PT (– 𝜇g/mL) and standard were determined by
measuring the decrease in the DPPH absorbance aer h
in the dark compared to a blank []. e same procedure
was followed for the ascorbic acid standard. is analysis was
carried out in triplicate (𝑛=3), and the results are expressed
as the means of % inhibition of the DPPH radical, which
wascalculatedasfollows:%inhibition=[(Abscontrol–
Abs sample)/Abs control] ×. e concentration of PT
that could scavenge % of the DPPH radical (IC50)was
calculated via a nonlinear regression analysis using the
GraphPad Prism Program version ..
2.6.3. Protection against Lipid Peroxidation. A low-speed
supernatant ( min at ×g) of brain homogenates
( mM Tris-HCl, pH ., : ; w/v) was preincubated at ∘C
for h in the presence or absence of 𝜇MFeCl
2,mMH
2O2,
PT (– 𝜇g/mL), and Tris-HCl mM. Subsequently, the
amount of thiobarbituric acid-reactive substances (TBARS)
was determined []. e inhibitory concentration (IC50),
which represents the concentration of PT that inhibits % of
lipid peroxidation, was determined via a nonlinear regression
analysis using the GraphPad Prism Program version ..
2.7. In Vivo Studies
2.7.1. Animals. two-month-old male Swiss mice (– g)
were obtained from the Bioterism Center of Unochapec´
o.
Sevenmicewerehousedpercage(× × cm) and
maintained in our own animal facility under controlled
environmental conditions ( ±∘C, hr light/dark cycle,
free access to food (Nuvilab CR) and water). All procedures
were carried out in accordance with institutional policies on
the handling of experimental animals (approved by the ethics
committee, process /).
2.7.2. Drugs. Fluoxetine was used as commercial Daforin
(Laborat´
orio EMS, SP, Brazil). All drugs were dissolved in
saline (NaCl .%). e drugs and saline were administered
intraperitoneally (i.p.) or orally (p.o.) at a constant volume of
. mL/ g body weight.
2.7.3. Ta i l S u s p e n s i o n Test ( T S T ) . e TST was used as
described by Steru et al. []. Mice (𝑛=7–10)wereorally
treated with vehicle (.% saline; w/v) or PT (, or
mg/kg). An additional group was treated with uoxetine
( mg/kg, i.p.). None of the selected doses modied locomo-
tionintheopeneldtest(datanotshown).emicewere
submitted to the TST for or min (for i.p. and p.o. treated
groups, resp.) aer treatments. Aer the TST, the animals
were euthanized, and their brains were removed immediately
in order to assess the oxidative stress parameter ex vivo.e
ex vivo analyses were performed in the PT mg/kg group
because the behavioral eects of this dose were comparable
to those of uoxetine.
2.8. Antioxidant Activity Ex Vivo
2.8.1. Antioxidant Enzymes. e antioxidant activity was
assessed ex vivo using homogenized mouse brains in
volumesofmMTrisbuer(pH.).ehomogenatewas
centrifuged at ×gand
∘Cformintoyieldalow-speed
supernatant for which all parameters were evaluated. e
SOD, CAT, and GPx activity were determined according to
Misra and Fridovich [], Aebi [], and Paglia and Valentine
[], respectively. e TrxR activity was determined using
,-dithiobis (-nitrobenzoic acid) (DTNB) and NADPH
[]. Gold (III) chloride trihydrate ( nM) was used to
inhibit the thioredoxin reductase activity [] and determine
the nonthioredoxin reductase DTNB reduction, which was
subtracted from the total DTNB reduction in order to obtain
the thioredoxin reductase activity. e amount of reduced
DTNB was calculated using an absorption coecient of . ×
/mol/cm.
2.8.2. Nonprotein iol Groups. e low-speed supernatant
fraction was mixed with % trichloroacetic acid ( : v/v),
followed by the centrifugation and neutralization of the
supernatant (to pH .) with M Tris. e nonprotein thiol
groups were immediately determined using a standard curve
of cysteine [].
2.8.3. Protein Quantication. e protein content was mea-
sured using bovine serum albumin as a standard [].
2.8.4. Lipid Peroxidation. Aer the addition of . mM
butylated hydroxytoluene to prevent further oxidation, the
supernatant was used to determine the amount of reactive
thiobarbituric acid []. e samples were extracted with n-
butanol, and the reaction product was determined at nm
using a standard curve of ,,,-tetraethoxypropane.
2.9. Statistical Analysis. e results (cumulative counts for
spontaneous locomotion, time in seconds for immobility, and
antioxidant activity in vitro and ex vivo) are expressed as the
mean ±S.E.M. Comparisons between the groups were made
by one-way ANOVA followed by Tukey’s post hoc test. e
dierences between the data were analyzed using Student’s
𝑡-test to assess the antioxidant activity in vitro (dierent
concentrations of PT ×dierent concentrations of ascorbic
acid). Results with 𝑝 < 0.05 were considered signicant. e
regression analyses were made using Statistica . soware
system (Statso Inc., ).
3. Results
e content of antioxidant compounds, such as total phe-
nolics and anthocyanins, was quantied. e total phenolic
compounds in the aqueous extract of P. t r u n c i o r a were
. ±. mg GAE/ g, while the anthocyanins
Evidence-Based Complementary and Alternative Medicine
0.0 10
1
20
(min)
300
200
100
0
(mAU)
520 nm, 4nm (1.00)
(a)
0.0 10 20
2
(min)
300
200
100
0
(mAU)
520 nm, 4nm (1.00)
(b)
0.0 10
3
20
(min)
300
200
100
0
(mAU)
520 nm, 4nm (1.00)
(c)
0.0 10
4
20
(min)
300
200
100
0
(mAU)
520 nm, 4nm (1.00)
(d)
0.0 10 20
5
(min)
300
200
100
0
(mAU)
520 nm, 4nm (1.00)
(e)
0.0 10 20
(min)
750
500
250
0
(mAU)
520 nm, 4nm (1.00)
1
2
3
4
5
(f)
F : Representative high performance liquid chromatography proles of the standards cyanidin chloride (a), malvidin chloride (b),
delphinidin -O-glucoside chloride (c), cyaniding -O-glucoside chloride (d), malvidin -O-glucoside chloride (e), and PT (f).
content was . ±. mg cyanidin -O-glucoside equiv-
alents/ g.
e HPLC ngerprinting of the P. t r u n c i o r a aqueous
extract (Figure ) revealed the presence of anthocyanins.
We identied cyanidin (Rt = 6.41 min; peak ), malvidin
(Rt = 9.73min; peak ), delphinidin -O-glucoside (Rt =
11.94min; peak ), cyanidin -O-glucoside (Rt = 15.08;peak
), and malvidin -O-glucoside (Rt = 20.57 min; peak ).
e composition of anthocyanins (mg/g) in the P. t r u n c i o r a
aqueous extract was cyanidin (. ±.), malvidin (. ±
.), delphinidin -O-glycoside (. ±.), cyanidin -O-
glycoside (. ±.),andmalvidin-O-glycoside (. ±
.).
A one-way ANOVA revealed that PT showed signi-
cant reducing power beyond a concentration of 𝜇g/mL
(Figure (a)). However, the ferric reducing power of ascorbic
Evidence-Based Complementary and Alternative Medicine
0
1
2
3
4
Ascorbic acid
PT
Absorbance
010 20 40 80 160
Concentration (𝜇g/mL)
∗𝜀
∗#
∗#
∗§
∗𝜓
(a)
0
20
40
60
80
100
Ascorbic acid
PT
DPPH inhibition (%)
10 20 40 80 160
Concentration (𝜇g/mL)
∗𝛾
∗
∗
∗#
∗#
(b)
F : Ferric reducing antioxidant power (FRAP (a)) and DPPHradical sc avenger activity (b) of PT. e results are expressed as the mean ±
S.E.M. 𝑛=3.(a)∗Dierent from ascorbic acid solution at the same concentration. ∗𝑝 < 0.05; Student’s 𝑡-test. Dierent symbols represent
dierent results within the PT group (𝑝 < 0.01, ANOVA/Tukey). (b) ∗Dierent from DPPH radical scavenger activity of ascorbic acid
solution at the same concentration. ∗𝑝 < 0.001, Student’s 𝑡-test. Dierent symbols represent dierent results within the PT group (𝑝 < 0.05,
ANOVA/Tukey).
acid was higher than that shown by PT in all concentrations
evaluated, as evident from Student’s 𝑡test. Figure (b) shows
the DPPH radical scavenging antioxidant activity. Although
the DPPH radical scavenging ability of PT was lower than
thatoftheascorbicacidsolution,itwasremarkableatall
evaluated concentrations. e calculated IC50 value for PT
was . 𝜇g/mL, compared to a value of . 𝜇g/mL for
ascorbic acid. At and 𝜇g/mL, PT inhibited between
and % of DPPH; at 𝜇g/mL, the inhibition increased
to % and exceeded % at concentrations of and
𝜇g/mL.
e extract inhibited the lipid peroxidation in a
homogenate of mouse brain at all concentrations (Figure ).
At 𝜇g/mL, PT inhibited approximately % of lipid
peroxidation, and the inhibition increased to % at and
𝜇g/mL and reached % at concentrations of and
𝜇g/mL. e calculated IC50 value for PT was . 𝜇g/mL.
e results in Figure show the eects of PT (, ,
and mg/kg, p.o.) and uoxetine ( mg/kg, i.p.) during
the tail suspension test in mice. PT signicantly reduced
the immobility time in the TST ( and mg/kg, p.o.,
𝐹4,40 =48,𝑝 < 0.0001). Fluoxetine signicantly reduced the
immobility time in the TST. e PT ( mg/kg, p.o.) was
compared with uoxetine. e spontaneous locomotion of
groups treated with PT did not dier from the controls (data
not shown).
Figure presents the eect of PT ( mg/kg, p.o.) and
uoxetine ( mg/kg, i.p.) administration on the antioxidant
enzyme activities in the homogenate of mouse brains. PT
and uoxetine did not result in signicant changes in the
SOD (Figure (a)), GPx (Figure (b)), and TrxR (Figure (c))
0
20
40
60
80
Inhibition of lipid peroxidation (%)
010 20 40 80 160
Concentration (𝜇g/mL)
∗
#
#
&&
F : Inhibition of Fenton reaction-induced lipid peroxidation
ofPT.eresultsareexpressedasthemeans±S.E.M. 𝑛=
5.∗Dierent symbols represent dierent results within the PT group
(𝑝 < 0.05,ANOVA/Tukey).
activities compared to the controls; uoxetine signicantly
increased the CAT (Figure (d))activitycomparedtothe
controls.
Figure shows the eect of PT ( mg/kg, p.o.) and u-
oxetine ( mg/kg, i.p.) on the lipid peroxidation and level of
nonprotein thiol groups (NPSH) in the homogenate of mouse
brains. Both the PT extract and the uoxetine attenuated lipid
peroxidation (Figure (a)). e levels of nonprotein thiol in
thePTextractanduoxetine(Figure (b))groupsdidnot
dierfromthatofthecontrol.
Evidence-Based Complementary and Alternative Medicine
0
50
100
150
200
250
Immobility time (s)
∗
∗
∗
FLU 32 PT 200 PT 400 PT 800
C
F : Eects of PT (, , and mg/kg, p.o.) and uoxe-
tine ( mg/kg, i.p.) in the TST. Each column represents the mean ±
S.E.M. 𝑛=7–10.∗𝑝 < 0.0001 × saline. ANOVA/ Tukey.
4. Discussion
Depression has been associated with lowered concentra-
tions of several endogenous antioxidant compounds, such as
coenzyme Q, vitamins C and E, or antioxidant enzymes,
such as GPx []. In addition, ROS and RNS have been
showntomodulateneurotransmittersystemsinvolvedinthe
neurobiology of depression []. In this context, this study
intended to evaluate the antidepressant-like eect of a P.
trunciora (PT) aqueous extract using the TST. Moreover,
considering that jaboticaba species are rich in avonoids and
related polyphenols [], the antioxidant eects of PT were
evaluated by in vitro and ex vivo assays.
OurresultsshowedforthersttimethatoralPT(
and mg/kg) had antidepressant-like activity in the TST.
is eect was dose related (𝑟 = −0.84,𝑝 < 0.001,
Pearson correlation analysis). Furthermore, the eect of PT
( mg/kg) was comparable to that of the antidepressant u-
oxetine ( mg/kg), a selective serotonin reuptake inhibitor.
To avoid false positives in the TST, our results showed that
PT treatment did not alter locomotor activity in the open eld
test (Figure S, in Supplementary Material available online at
http://dx.doi.org/.//).
Although the mechanisms of the antidepressant-like
activity of PT remain unclear, the bioactive compounds
currently identied as well as their antioxidant properties
may be involved in this eect. Flavonoids, such as antho-
cyanins, stand out among the major classes of phenolic
compounds of plants []. e cyanidin--O-glycoside (peak
) was the dominant anthocyanin present in our extract.
Other anthocyanins, such as delphinidin -O-glucoside and
cyanidin- -O-glucoside, were also detected. Importantly, the
antioxidant eects of these compounds have been described
in the literature []. Data of linear regression revealed a
substantial contribution of TPC and TMA for the reducing
antioxidant power of PT assessed by FRAP method (𝑅=
0.96 and 𝑅 = 0.97,𝑝 = 0.00001, resp.; see Figures S-S,
supplementary data). TPC and TMA also contributed to %
inhibition of DPPH and % inhibition of lipid peroxidation
(𝑅 = 0.83 and 𝑅 = 0.93, resp.), as demonstrated
by nonlinear regression (see Figures S–S, supplementary
data).
e FRAP assay measures the ability of an antioxidant
substance to donate one electron []. Because the antioxi-
dant activity of a substance correlates with its reducing prop-
erties, the reduction of the ,,-tripyridyl-s-triazine-Fe(III)
complex due to PT indicates the presence of compounds that
candonateelectrons,suchasphenoliccompounds.Accord-
ingly, the antioxidant properties of the Syzygium cumini fruit
skin may in part be due to the antioxidant vitamins, tannins,
phenolics, and anthocyanin compounds present in the fruit
[].
e reducing power of PT was corroborated by the
DPPH radical scavenging assay, which also evaluates the
ability of antioxidants to transfer a single electron. is
armation is based on the fact that both the reducing and
the scavenging DPPH abilities of the extract were observed
in the entire evaluated concentration range (–𝜇g/mL).
erefore, these results strongly suggest that the DPPH
radical scavenging capacity of PT is related to its reducing
properties, as evidenced in the FRAP assay. Conversely, PT
could not remove H2O2or O2∙− nor avoid the H2O2-induced
oxidation of GSH (data not shown).
Lipid peroxidation is an index of oxidative stress and
may result in damage to components of the cell membrane,
which may lead to calcium inux and cell death. Lipid
peroxidation is associated with several diseases, including
neurodegenerative disorders [], and antioxidants may pro-
tect against lipid peroxidation by scavenging the free radicals
[]. e in vitro resultsofthecurrentstudyshowedthat
PT inhibited the lipid peroxidation at all concentrations.
is protective eect suggests that other possible mechanisms
of action of the antioxidant activity are associated with
the ability of this extract to scavenge the hydroxyl (∙OH)
radical. Interestingly, PT ( mg/kg) also attenuated lipid
peroxidation when administered to mice. is protection
was similar to that observed for uoxetine (mg/kg) and
occurred at a dose that showed an antidepressant-like eect.
Fluoxetine decreased lipid peroxidation probably due to the
increased CAT activity, which removes H2O2to reduce its
availability for the formation of the ∙OH radical. Similarly,
uoxetine exerted a restorative action on the oxidative
eects in the peripheral defense cells of animals submitted
to the restraint stress model, which was also associated
with enhanced endogenous antioxidant defenses (CAT and
SOD) and the restoration of GSH levels []. Oxidative
damage to lipids and decreased antioxidant enzyme activ-
ity have been reported in patients with major depressive
disorder [], and preclinical studies have suggested that
antioxidants may have antidepressant properties []. Taking
into account these ndings, the inhibition of lipid perox-
idation by PT as well as the ability of PT to scavenge
free radicals strongly suggests a link between the antiox-
idant activity and the antidepressant-like eects observed
here.
e present study showed the in vitro and ex vivo antiox-
idant and antidepressant-like eects of PT in mice. ese
antioxidant properties might be related to the antidepressant-
like activity of Plinia trunciora.
Evidence-Based Complementary and Alternative Medicine
0
10
20
30
40
SOD (U/mg protein)
FLU PT 800
C
(a)
0.00
0.02
0.04
0.06
0.08
0.10
GPx (nmol NADPH/min/mg protein)
FLU PT 800
C
(b)
0
10
20
30
40
TrxR (nmol DTNB/min/mg protein)
FLU PT 800
C
(c)
0
2
4
6
CAT (k/g protein)
∗
FLU PT 800
C
(d)
F : Eects of PT ( mg/kg, p.o.) and uoxetine ( mg/kg, i.p.) treatment on antioxidant enzyme activities SOD (a), GPx (b), TrxR
(c), and CAT (d) in homogenate of brain mice. e results are expressed as the means ±S.E.M. 𝑛=6.∗𝑝 < 0.05 × saline. ANOVA/Tukey.
∗
∗
0.0
0.1
0.2
0.3
TBARS (nmol MDA/mg protein)
FLU PT 800
C
(a)
0
5
10
15
20
NPSH (nmol NPSH/mg protein)
FLU PT 800
C
(b)
F : Eects of PT ( mg/kg, p.o.) and uoxetine ( mg/kg, i.p.) on lipid peroxidation (a) and nonprotein thiol groups (NPSH) level
(b). e results are expressed as the means ±S.E.M. 𝑛=6.∗𝑝 < 0.05 × saline. ANOVA/Tukey.
Evidence-Based Complementary and Alternative Medicine
Conflict of Interests
eauthorshavedeclaredthatnocompetinginterestsexist.
References
[] A.J.Ferrari,F.J.Charlson,R.E.Normanetal.,“Burdenof
depressive disorders by country, sex, age, and year: ndings
from the global burden of disease study ,” PLoS Medicine,
vol. , no. , Article ID e, .
[] A.J.Smith,I.Sketris,C.Cooke,D.Gardner,S.Kisely,andS.
E. Tett, “A comparison of antidepressant use in Nova Scotia,
Canada and Australia,” Pharmacoepidemiology and Drug Safety,
vol.,no.,pp.–,.
[] J. J. Schildkraut, E. K. Gordon, and J. Durell, “Catecholamine
metabolism in aective disorders. I. Normetanephrine and
VMA excretion in depressed patients treated with imipramine,”
Journal of Psychiatric Research,vol.,no.,pp.–,.
[] T. M. Michel, S. Frangou, D. iemeyer et al., “Evidence for
oxidative stress in the frontal cortex in patients with recurrent
depressive disorder—a postmortem study,” Psychiatry Research,
vol. , no. -, pp. –, .
[] J. Nordberg and E. S. J. Arn´
er, “Reactive oxygen species,
antioxidants, and the mammalian thioredoxin system,” Free
Radical Biology and Medicine, vol. , no. , pp. –, .
[] B. Halliwell, “Role of free radicals in the neurodegenerative
diseases: therapeutic implications for antioxidant treatment,”
Drugs and Aging,vol.,no.,pp.–,.
[] S. V. Avery, “Molecular targets of oxidative stress,” Biochemical
Journal,vol.,no.,pp.–,.
[] P. Mecocci and M. C. Polidori, “Antioxidant clinical trials in
mild cognitive impairment and Alzheimer’s disease,” Biochim-
ica et Biophysica Acta,vol.,no.,pp.–,.
[] M. Valko, D. Leibfritz, J. Moncol, M. T. D. Cronin, M. Mazur,
and J. Telser, “Free radicals and antioxidants in normal physi-
ological functions and human disease,” International Journal of
Biochemistry and Cell Biology,vol.,no.,pp.–,.
[] C. Vollert, M. Zagaar, I. Hovatta et al., “Exercise prevents sleep
deprivation-associated anxiety-like behavior in rats: poten-
tial role of oxidative stress mechanisms,” Behavioural Brain
Research,vol.,no.,pp.–,.
[] D. J. Mabberley, e Plant Book, Cambridge University Press,
Cambridge, UK, nd edition, .
[] L. C. Stasi and C. A. Hiruma-Lima, “Myrtales medicinais,” in
Plantas Medicinais na Amazˆ
oniaenaMataAtl
ˆ
antica,L.C.Stasi
and C. A. Hiruma-Lima, Eds., pp. –, Editora UNESP, S˜
ao
Paulo, Brazil, nd edition, .
[] E. M. Kuskoski, A. G. Asuero, A. M. Troncoso, J. Mancini-Filho,
and R. Fett, “Aplicaci´
on de diversos m´
etodos qu´
ımicos para
determinar actividad antioxidante en pulpa de frutos,” Ciˆ
encia
eTecnologiadeAlimentos,vol.,no.,pp.–,.
[] V. L. Singleton and J. A. J. Rossi, “Colorimetry of total phenolics
with phosphomolybdic-phosphotungstic acid reagents,” Ameri-
can Journal of Enology and Viticulture, vol. , no. , pp. –,
.
[]J.Lee,R.W.Durst,andR.E.Wrolstad,“Determinationof
total monomeric anthocyanin pigment content of fruit juices,
beverages, natural colorants, and wines by the pH dierential
method: collaborative study,” Journal of AOAC International,
vol. , no. , pp. –, .
[] J. P. Kamdem, E. O. Olalekan, W. Hassan et al., “Trichilia catigua
(Catuaba) bark extract exerts neuroprotection against oxidative
stress induced by dierent neurotoxic agents in rat hippocampal
slices,” Industrial Crops and Products,vol.,pp.–,.
[] A. A. Boligon, T. F. Kubic
¸a, D. N. Mario et al., “Antimicrobial
and antiviral activity-guided fractionation from Scutia buxifolia
Reissek extracts,” Acta Physiologiae Plantarum,vol.,no.,pp.
–, .
[] I. F. F. Benzie and J. J. Strain, “e ferric reducing ability of
plasma (FRAP) as a measure of ‘antioxidant power’: the FRAP
assay,” Analytical Biochemistry,vol.,no.,pp.–,.
[] W.Brand-Williams,M.E.Cuvelier,andC.Berset,“Useofafree
radical method to evaluate antioxidant activity,” LWT—Food
Science and Technology,vol.,no.,pp.–,.
[] H. Ohkawa, N. Ohishi, and K. Yagi, “Assay for lipid peroxides
in animal tissues by thiobarbituric acid reaction,” Analytical
Biochemistry,vol.,no.,pp.–,.
[] L. Steru, R. Chermat, B. ierry, and P. Simon, “e tail
suspension test: a new method for screening antidepressants in
mice,” Psychopharmacology,vol.,no.,pp.–,.
[] H. P. Misra and I. Fridovich, “e role of superoxide anion in the
autoxidation of epinephrine and a simple assay for superoxide
dismutase,” Journal of Biological Chemistry,vol.,no.,pp.
–, .
[] H. Aebi, “Catalase in vitro,” Methods in Enzymology,vol.,pp.
–, .
[] D. E. Paglia and W. N. Valentine, “Studies on the quantitative
and qualitative characterization of erythrocyte glutathione per-
oxidase,” e Journal of Laboratory and Clinical Medicine,vol.
,no.,pp.–,.
[] A. Holmgren and M. Bj¨
ornstedt, “ioredoxin and thioredoxin
reductase,” Methods in Enzymology,vol.,pp.–,.
[] Y. Omata, M. Folan, M. Shaw et al., “Sublethal concentrations of
diverse gold compounds inhibit mammalian cytosolic thiore-
doxin reductase (TrxR),” Toxicol o g y I n Vit r o ,vol.,no.,pp.
–, .
[] G. L. Ellman, “Tissue sulydryl groups,” Archives of Biochem-
istry and Biophysics,vol.,no.,pp.–,.
[] O.H.Lowry,N.J.Rosebrough,A.L.Farr,andR.J.Randall,
“Protein measurement with the Folin phenol reagent,” e
JournalofBiologicalChemistry,vol.,no.,pp.–,.
[]M.Maes,P.Galecki,Y.S.Chang,andM.Berk,“Areview
on the oxidative and nitrosative stress (O&NS) pathways
in major depression and their possible contribution to the
(neuro)degenerative processes in that illness,” Progress in
Neuro-Psychopharmacology and Biological Psychiatry,vol.,
no.,pp.–,.
[] V. O. Kotan, E. Sarandol, E. Kirhan, G. Ozkaya, and S. Kirli,
“Eects of long-term antidepressant treatment on oxidative
status in major depressive disorder: a -week follow-up study,”
Progress in Neuro-Psychopharmacology and Biological Psychia-
try,vol.,no.,pp.–,.
[] K. A. Reynertson, A. M. Wallace, S. Adachi et al., “Bioac-
tive depsides and anthocyanins from jaboticaba (Myrciaria
cauliora),” Journal of Natural Products,vol.,no.,pp.–
, .
[]S.AparecidadeAssis,J.C.R.Vellosa,I.L.Brunettietal.,
“Antioxidant activity, ascorbic acid and total phenol of exotic
fruits occurring in Brazil,” International Journal of Food Sciences
and Nutrition, vol. , no. , pp. –, .
Evidence-Based Complementary and Alternative Medicine
[] A. Casta˜
neda-Ovando, M. D. L. Pacheco-Hern´
andez, M. E.
P´
aez-Hern´
andez, J. A. Rodr´
ıguez, and C. A. Gal´
an-Vidal,
“Chemical studies of anthocyanins: a review,” Food Chemistry,
vol.,no.,pp.–,.
[] A. Banerjee, N. Dasgupta, and B. De, “In vitro study of
antioxidant activity of Syzygium cumini fruit,” Food Chemistry,
vol.,no.,pp.–,.
[]B.Uttara,A.V.Singh,P.Zamboni,andR.T.Mahajan,
“Oxidative stress and neurodegenerative diseases: a review of
upstream and downstream antioxidant therapeutic options,”
Current Neuropharmacology,vol.,no.,pp.–,.
[] M. Z. Gul, L. M. Bhakshu, F. Ahmad, A. K. Kondapi, I.
A. Qureshi, and I. A. Ghazi, “Evaluation of Abelmoschus
moschatus extracts for antioxidant, free radical scavenging,
antimicrobial and antiproliferative activities using in vitro
assays,” BMC Complementary and Alternative Medicine, vol. ,
article , .
[] S. Nov´
ıo,M.J.N
´
u˜
nez, G. Amigo, and M. Freire-Garabal,
“Eects of uoxetine on the oxidative status of peripheral
blood leucocytes of restraint-stressed mice,” Basic and Clinical
Pharmacology and Toxicology,vol.,no.,pp.–,.
[] A. Sarandol, E. Sarandol, S. S. Eker, S. Erdinc, E. Vatansever, and
S. Kirli, “Major depressive disorder is accompanied with oxida-
tive stress: short-term antidepressant treatment does not alter
oxidative–antioxidative systems,” Human Psychopharmacology,
vol. , no. , pp. –, .
[]A.Zar,A.Ara,andN.Banu,“In vivo antioxidant status: a
putative target of antidepressant action,” Progress in Neuro-
Psychopharmacology and Biological Psychiatry,vol.,no.,pp.
–, .
Content uploaded by Walter roman junior
Author content
All content in this area was uploaded by Walter roman junior on Sep 02, 2015
Content may be subject to copyright.
