Rose oil (from Rosa × damascena Mill.) vapor attenuates depression-induced oxidative toxicity in rat brain

Abstract

Oxidative stress is a critical route of damage in various physiological stress-induced disorders, including depression. Rose oil may be a useful treatment for depression because it contains flavonoids which include free radical antioxidant compounds such as rutin and quercetin. We investigated the effects of absolute rose oil (from Rosa × damascena Mill.) and experimental depression on lipid peroxidation and antioxidant levels in the cerebral cortex of rats. Thirty-two male rats were randomly divided into four groups. The first group was used as control, while depression was induced in the second group using chronic mild stress (CMS). Oral (1.5 ml/kg) and vapor (0.15 ml/kg) rose oil were given for 28 days to CMS depression-induced rats, constituting the third and fourth groups, respectively. The sucrose preference test was used weekly to identify depression-like phenotypes during the experiment. At the end of the experiment, cerebral cortex samples were taken from all groups. The lipid peroxidation levels in the cerebral cortex in the CMS group were higher than in control whereas their levels were decreased by rose oil vapor exposure. The vitamin A, vitamin E, vitamin C and β-carotene concentrations in the cerebral cortex were lower in the CMS group than in the control group whereas their concentrations were higher in the rose oil vapor plus CMS group. The CMS-induced antioxidant vitamin changes were not modulated by oral treatment. Glutathione peroxidase activity and reduced glutathione did not change statistically in the four groups following CMS or either treatment. In conclusion, experimental depression is associated with elevated oxidative stress while treatment with rose oil vapor induced protective effects on oxidative stress in depression.

Full text

ORIGINAL PAPER
Rose oil (from Rosa 3damascena Mill.) vapor attenuates
depression-induced oxidative toxicity in rat brain
Mustafa Nazırog
˘lu •Su
¨leyman Kozlu •
Emre Yorgancıgil •Abdu
¨lhadi Cihangir Ug
˘uz •
Kadir Karakus¸
Received: 31 January 2012 / Accepted: 14 March 2012 / Published online: 8 April 2012
ÓThe Japanese Society of Pharmacognosy and Springer 2012
Abstract Oxidative stress is a critical route of damage in
various physiological stress-induced disorders, including
depression. Rose oil may be a useful treatment for
depression because it contains flavonoids which include
free radical antioxidant compounds such as rutin and
quercetin. We investigated the effects of absolute rose oil
(from Rosa 9damascena Mill.) and experimental depres-
sion on lipid peroxidation and antioxidant levels in the
cerebral cortex of rats. Thirty-two male rats were randomly
divided into four groups. The first group was used as
control, while depression was induced in the second group
using chronic mild stress (CMS). Oral (1.5 ml/kg) and
vapor (0.15 ml/kg) rose oil were given for 28 days to CMS
depression-induced rats, constituting the third and fourth
groups, respectively. The sucrose preference test was used
weekly to identify depression-like phenotypes during the
experiment. At the end of the experiment, cerebral cortex
samples were taken from all groups. The lipid peroxidation
levels in the cerebral cortex in the CMS group were higher
than in control whereas their levels were decreased by rose
oil vapor exposure. The vitamin A, vitamin E, vitamin C
and b-carotene concentrations in the cerebral cortex were
lower in the CMS group than in the control group whereas
their concentrations were higher in the rose oil vapor plus
CMS group. The CMS-induced antioxidant vitamin chan-
ges were not modulated by oral treatment. Glutathione
peroxidase activity and reduced glutathione did not change
statistically in the four groups following CMS or either
treatment. In conclusion, experimental depression is asso-
ciated with elevated oxidative stress while treatment with
rose oil vapor induced protective effects on oxidative stress
in depression.
Keywords Rose oil Depression Glutathione
peroxidase Oxidative stress Antioxidant vitamins
Abbreviations
CMS Chronic mild stress
GSH-Px Glutathione peroxidase
GSH Glutathione
MAO Monoamine oxidase
PUFA Polyunsaturated fatty acid
ROS Reactive oxygen species
SSRI Selective-serotonin reuptake inhibitor
Introduction
Reactive oxygen species (ROS) including superoxide anion,
hydrogen peroxide and singlet oxygen act as subcellular
messengers in pathophysiological complex processes such
as mitogenic signal transduction, gene expression, and reg-
ulation of cell proliferation when they are generated in
excess or when enzymatic and non-enzymatic defense
M. Nazırog
˘lu (&)A. C. Ug
˘uz
Department of Biophysics, Medical Faculty,
Suleyman Demirel University, 32260 Isparta, Turkey
e-mail: mnaziroglu@med.sdu.edu.tr
M. Nazırog
˘lu
Neuroscience Research Center,
Suleyman Demirel University, Isparta, Turkey
S. Kozlu E. Yorgancıgil
Medical Faculty, Suleyman Demirel University,
Isparta, Turkey
K. Karakus¸
Department of Psychiatry, Medical Faculty,
Suleyman Demirel University, Isparta, Turkey
123
J Nat Med (2013) 67:152–158
DOI 10.1007/s11418-012-0666-7

systems are impaired [1,2]. Oxidative stress is a disparity
between the rates of ROS production and elimination
through endogenous enzymatic mechanisms such as gluta-
thione peroxidase (GSH-Px) and catalase as well as the low-
molecular-weight reductants glutathione (GSH), vitamin A,
vitamin C, vitamin E and b-carotene. There are numerous
studies indicating that ROS-induced neuronal damage has an
important role in the pathophysiology of depression, prob-
ably via membrane omega–3 polyunsaturated fatty acids
pathology [1], decreased activity of GSH-Px [3], and anti-
oxidant vitamins [4,5], suggesting oxidative damage. GSH-
Px, one of the major intracellular antioxidant enzymes,
detoxifies hydrogen peroxide (H
2
O
2
) to water and also
scavenges other peroxides. Although most of the oxygen
used in brain tissue is converted to CO
2
and water, small
amounts of oxygen form ROS. The existence of polyunsat-
urated fatty acids (PUFAs) which are targets of the ROS in
the brain make this organ more sensitive to oxidative damage
[1]. In depression-induced stress disorders, ROS induces
several mechanisms of oxidative damage such as mito-
chondrial dysfunction, dysregulation of calcium homeosta-
sis [6,7], disruption of energy pathways, damage to neuronal
precursor impairment of neurogenesis [8] and induction of
signal events in apoptotic cell death [6]. These ROS pro-
duction events make a significant contribution towards the
resultant disease pathophysiology, as evidenced by atrophy/
morphological changes in the brain characteristic of stress-
induced depression [9]. Hence, psychological stress, which
accompanies severe depression, may increase lipid peroxi-
dation [7,10].
Rose oil is produced from Damask rose (Rosa 9da-
mascena Mill.), which is grown in Middle East countries,
especially Iran and Turkey. Rose oil is widely used in
perfumery and the cosmetic industry [11]. One increasingly
popular type of alternative therapy is aromatherapy, but
scientific validation in this field is still rare. Rose oil con-
tains flavonoids such as geraniol and citronellol [11], which
demonstrated a ROS scavenging activity in a model of
autotoxication of rat cerebral membranes [12]. In recent
years, the antidepressant effects of rose oil have also been
demonstrated although the molecular mechanisms of these
effects have not yet been clarified [13]. Rose oil, with a
potential antioxidant activity, may therefore be of value in
psychiatric disorders including depression in which free
radical generation is implicated, and this subject needs to
be investigated.
Rose oil, as an antidepressant medication with a
potential antioxidant activity, was therefore hypothesized
to be a better alternative to other antidepressant flower oils
like jasmine, chamomile and bergamot oils for patients
with depression exhibiting elevated oxidative stress levels.
We therefore aimed at investigating the effects of rose oil
on cerebral cortex lipid peroxidation, and GSH, GSH-Px,
vitamins A, C and E, and b-carotene values in experimental
depression in rats.
Materials and methods
Animals
Thirty-two male Wistar albino rats weighing 200–250 g
(10–12 weeks) were used for the experimental procedures.
Rats were allowed 1 week to acclimatize to their sur-
roundings before beginning any experimentation. Animals
were housed in individual plastic cages with bedding.
Standard rat food and tap water were available ad libitum
for the duration of the experiments. Sucrose (1 %) was
available ad libitum for 1 week preceding the experimental
procedures to allow for adaptation to its taste. The tem-
perature was maintained at 22 ±2°C. A 12/12-h light/
dark cycle was maintained, with lights on at 06:00, unless
otherwise noted. Study protocol (Protocol Number:
2010:07–08) was approved by the local ethical committee
of Suleyman Demirel University. Animals were maintained
and used in accordance with the Animal Welfare Act and
the Guide for the Care and Use of Laboratory Animals
prepared by the Suleyman Demirel University.
Experimental design
Animals were divided equally into four groups. Group I was
control animals and they received placebo. Groups II, III and
IV rats had depression induced by chronic mild stress (CMS).
Rose oil (1.5 ml/kg) was dissolved in ethyl alcohol and made
up to final volume (0.2 ml) with physiological saline (0.9 %,
w/v), and was orally administered via gastric gavage to ani-
mals in the third group each day for 28 days [14]. The fourth
group was exposed to rose oil (0.15 ml/kg) vapor within an
isolated cage for 15 min each day for 28 days [15]. Control
animals were exposed to vapor cage stress and received
physiological saline gastric gavage, respectively.
Analysis of content of rose oil
The pure rose oil was bought from Gulbirlik Inc. (Isparta,
Turkey) and its chemical content was analyzed by a gas
chromatograph (GC)–mass spectrophotometer (MS) sys-
tem (Shimadzu, GC-MS QP 5050, Kyoto, Japan) [11].
Induction of depression
Chronic mild stress (CMS)
The procedures for inducing CMS are summarized in
Table 1. The CMS procedure employed here has been
J Nat Med (2013) 67:152–158 153
123

described previously [4,5] and was designed to maximize
the unpredictable nature of the stressors. The CMS group
was exposed to the following stressors in random order:
continuous overnight illumination, 408cage tilt, paired
housing, damp bedding (300 ml water spilled into bed-
ding), exposure to an empty water bottle immediately
following a period of acute water deprivation, stroboscopic
illumination (300 flashes/min), and white noise (approx.
90 dB). The stressors were presented in the order shown
during the first week and repeated during each of the fol-
lowing weeks for a total of 4 weeks. Control animals were
left undisturbed in the home cages with the exception of
general handling (i.e., regular cage cleaning and measuring
body weight), which was comparable to the activities of the
CMS group.
Sucrose preference tests
Sucrose preference tests as employed previously [16] were
used to operationally define anhedonia. Specifically,
anhedonia was defined as a reduction in sucrose intake and
sucrose preference relative to the intake and preference of
the control group. The sucrose preference test consisted of
first removing the food and water from each rat’s cage
(both CMS and control groups) for a period of 20 h. Water
and 1 % sucrose were then placed on the cages in pre-
weighed glass bottles, and animals were allowed to con-
sume the fluids freely for a period of 1 h. Two baseline
preference tests were performed, separated by at least
5 days, and the results were averaged. A preference test
was also conducted following the 4-week CMS period.
Anesthesia and tissue and blood sampling
Animals were rested and fasted for 12 h after the last
supplementation before killing. Rats were anesthetized
with a cocktail of ketamine hydrochloride (50 mg/kg;
Ketalar, Eczacibasi Inc., Istanbul, Turkey) and xylazine
(5 mg/kg; Rompun, Eczacibasi) administered intraperito-
neally (i.p.) before killing, and the whole brain was
dissected out of the head of the animals and split in the
mid-sagittal plane. The cerebral cortex of the brain was
then dissected from the whole brain.
The cortex of the brain was washed twice with cold
saline solution, placed into glass bottles, labeled and stored
in a deep freeze (-33 °C) until processing (maximum
10 h). After weighing, the cortex was placed on ice, cut
into small pieces using scissors, and homogenized (2 min
at 5000 rpm) in five volumes (1:5, w/v) of ice-cold Tris–
HCl buffer (50 mM, pH 7.4) using a glass ultrasonic
homogenizer. All preparation procedures were performed
at 4 °C.
Lipid peroxidation level determination
Malondialdehyde is a secondary product of lipid peroxi-
dation and is used as an index of lipid peroxidation. Lipid
peroxidation levels as malondialdehyde in the brain cortex
homogenate were measured by the method of Placer et al.
[17] as described in previous studies [4,5]. The samples
were incubated at 100 °C for 30 min in acid medium
containing 0.45 % sodium dodecyl sulfate and 0.67 %
thiobarbituric acid. Quantification of thiobarbituric acid
reactive substances was done by comparing the absorption
to the standard curve of malondialdehyde equivalents
generated by acid catalyzed hydrolysis of 1,1,3,3-tetra-
methoxypropane. The values of lipid peroxidation in the
cerebral cortex were expressed as lmol/g protein.
Reduced glutathione (GSH), glutathione peroxidase
(GSH-Px) and protein assay
Cerebral cortex GSH levels were measured as nonprotein
thiols based on the protocol developed by Sedlak and
Lindsay [18]. Cerebral cortex homogenates were precipi-
tated in cooled trichloroacetic acid 10 % and centrifuged at
15,000gfor 2 min, and the supernatant was incubated with
DTNB in a 1 M phosphate buffer, pH 7.0. Absorbances
were measured at 412 nm. A standard curve of reduced
glutathione was used to calculate GSH levels.
Table 1 Procedures for inducing chronic mild stress in rats
Sunday Monday Tuesday Wednesday Thursday Friday Saturday
Taking water bottles (h) 16:00 ?08:00
Adding empty water bottles (h) 08:00–09:00
Continuous illumination (h) 16:00 ?08:00 17:00 ?10:00
408cage tilt 11:00–17:00
Paired housing ??? 08:00 18:00 ?14:00 10:00 ???
Damp bedding (300 ml) 17:00 ?10:00 (h)
White noise (90 dB) 10:00–13:00 (h)
Stroboscopic illumination
(300 flashes/min)
11:00–16:00 (h) 13:00–15:00
154 J Nat Med (2013) 67:152–158
123

GSH-Px activities of cerebral cortex were measured
spectrophotometrically (UV-1800, Shimadzu, Kyoto, Japan)
at 37 °C and 412 nm according to the method of Lawrence
and Burk [19]. GSH-Px uses GSH to reduce tert-butyl
hydroperoxide, producing oxidized glutathione, which is
readily reduced to GSH by GSH reductase using NADPH as
a reducing equivalent donor. The protein content in the
cerebral cortex was measured by the method of Lowry et al.
[20] with bovine serum albumin as the standard.
Determination of vitamins A, E and C
and b-carotene concentrations
Vitamins A (retinol) and E (a-tocopherol) were determined
in the cerebral cortex samples by a modification of the
method described by Desai [21] and Suzuki and Katoh
[22]. Cerebral cortex samples (250 mg) were saponified by
the addition of 0.3 ml 60 % (w/v in water) KOH, followed
by heating at 70 °C for 30 min. After cooling the samples
on ice, 2 ml of water and 1 ml of n-hexane were added and
mixed with the samples and then rested for 10 min to allow
phase separation. An aliquot of 0.5 ml of n-hexane extract
was taken and vitamin A concentrations were measured at
325 nm. Reactants were then added and the absorbance
value of hexane was measured in a spectrophotometer at
535 nm. Calibration was performed using standard solu-
tions of all-trans-retinol and a-tocopherol in hexane.
The concentrations of b-carotene in the brain samples
were determined according to the method of Suzuki and
Katoh [22]. Two ml of hexane were mixed with 250 mg
cerebral cortex sample. The concentration of b-carotene in
hexane was measured at 453 nm in a spectrophotometer.
Quantification of ascorbic acid in the brain samples was
performed using the method of Jagota and Dani [23]. The
absorbance of the samples was measured spectrophoto-
metrically at 760 nm.
Statistical analyses
All results are expressed as means ±SD. To determine the
effect of treatment, data were analyzed using the LSD test.
p-Values of less than 0.05 were regarded as significant.
Significant values were assessed with the Mann–Whitney
Utest. Data were analyzed using the SPSS statistical pro-
gram (version 9.05, SPSS Inc. Chicago, IL, USA).
Results
Among the 15 chemical constituents identified by GC-MS
analysis of rose essential oil, citronellol was found to be the
major compound (33.74 %), followed by geraniol
(24.85 %), nerol (10.77 %) and nonadecene (9.30 %).
Trace amounts of other chemical compounds were also
identified. These results are in agreement with previous
studies [11] (Table 2).
Table 2 Major components of rose oil
Compounds %
Ethanol 0.65
a-Pinene 0.81
b-Pinene 0.21
Myrcene 0.47
PEA 1.12
Linalool 0.85
Terpinen-4-ol 0.39
Nerol 10.77
Citronellol 33.74
Geraniol 24.85
Eugenol 0.89
Citronellyl acetate 0.82
Geranyl acetate 3.18
Methyl eugenol 2.04
Germacrane-D 0.39
Farnesol 0.56
Heptadecane 1.25
9-Nonadecene 2.18
Nonadecene 9.30
Eicosane 0.62
Heneicosane 3.63
Table 3 Sucrose (1 %, w/v) test results in the control, chronic mild stress (CMS) depression, depression plus oral and vapor rose oil supple-
mented groups (n=8, mean ±SD)
Weeks Control (ml/kg) CMS (ml/kg) CMS ?oral rose
oil (ml/kg)
CMS ?vapor rose
oil (ml/kg)
Basal 25.18 ±4.05 28.97 ±8.78 28.65 ±10.26 25.66 ±10.11
1st 25.31 ±6.47 25.30 ±6.47 25.00 ±10.20 21.70 ±10.70
2nd 24.56 ±8.07 29.60 ±5.16 27.80 ±6.57 30.70 ±13.50
3rd 23.93 ±9.45 19.56 ±7.53
a
26.56 ±8.53 33.00 ±9.94
a
4th 21.43 ±9.69 18.94 ±8.37
a
22.80 ±9.76 35.40 ±8.63
a
a
p\0.05 versus basal values
J Nat Med (2013) 67:152–158 155
123

Sucrose (1 %, w/v) test results are shown in Table 3;
consumption of water with sucrose at 3rd and 4th weeks in
ml/kg body weight was significantly (p\0.05) lower in
the depression group than basal values. In addition, con-
sumption of water with sucrose at 3rd and 4th weeks in ml/kg
body weight was significantly (p\0.05) higher in the rose
vapor supplemented groups than in the basal group.
The mean lipid peroxidation values in the cerebral
cortex of the four groups are shown in Fig. 1. The results
showed that the lipid peroxidation levels in CMS and CMS
plus oral rose oil groups were significantly (p\0.05)
higher than in control. Exposure to rose oil vapor in
depressed rats caused a decrease in the lipid peroxidation
levels (p\0.001) compared to the depression-only group.
The mean vitamin A, vitamin C, vitamin E and b-car-
otene concentrations in the cerebral cortex of the four
groups are shown in Table 4. The results showed that
vitamin A, vitamin C, vitamin E and b-carotene concen-
trations in the cerebral cortex of the depression and oral
rose oil groups were significantly (p\0.001) lower than in
control. The vitamin A, vitamin C, vitamin E and b-caro-
tene concentrations in the cerebral cortex in CMS plus rose
oil vapor group were significantly (p\0.001) higher than
in the CMS group.
The mean GSH and GSH-Px values in the cortex of the
brain in the four groups are also shown in Table 4. There
were no statistically significance differences in GSH and
GSH-Px values between the groups.
Discussion
We observed that lipid peroxidation levels in cerebral
cortex were increased by CMS-induced experimental
depression and oral rose oil supplementation, while the
antioxidant vitamins A, C and E and b-carotene levels
decreased. Therefore, CMS-induced depression in the
animals is characterized by decreased antioxidants and
increased lipid peroxidation levels. As another novel result
of the current study, 28 days’ rose oil vapor supplemen-
tation caused a decrease in lipid peroxidation levels, and
the antioxidant values increased.
Numerous attempts have been made to set up an animal
model for depression or at least for some disease aspects.
The weekly sucrose preference tests revealed that control
animals typically exhibited a high preference for palatable
sucrose solutions [16], while this preference was markedly
reduced following exposure to uncontrollable restraint
stress, in agreement with previous studies [4,5,10]. This
progressive decline in the sensitivity to a rewarding stim-
ulus (sucrose) observed due to chronic stress exposure is
thought to represent anhedonia (the loss of interest or
pleasure) in animals, one of the two core symptoms
required for diagnosis of a major depressive episode in
human and rodents [16].
Exposure to stress can induce psychiatric conditions,
including depression. Alterations in oxidative stress are
increasingly being recognized as a critical route of damage
towards the pathology of stress-induced psychiatric disor-
ders [24]. Significant correlations were found between the
severity of depression, as well as length of index episode
50
75
100
125
150
175
200
225
250
Control Depression Depression+oral Depression+vapor
(µmol/g protein)
a
b
a
a p<0.05 versus control.
b
p
<0.001 versus de
p
ression
g
rou
p
.
Fig. 1 The effects of oral and vapor rose oil administrations on lipid
peroxidation levels in brain of control and rats with depression
induced by chronic mild stress (CMS) (mean ±SD, n=8)
Table 4 The effects of oral and vapor rose oil supplementation on glutathione peroxidase (GSH-Px), reduced glutathione (GSH) and antioxidant
vitamin values in cerebral cortex of rats with chronic mild stress (CMS)-induced depression (mean ±SD)
Parameters Control (n=8) Depression (n=8) CMS ?oral (n=8) CMS ?vapor
GSH (lmol/g protein) 9.78 ±0.95 8.69 ±0.49 9.60 ±0.66 9.36 ±0.36
GSH-Px (IU/g protein) 64.84 ±6.63 62.31 ±2.99 64.98 ±3.41 66.78 ±4.17
Vitamin A (lmol/g tissue) 2.42 ±0.21 0.73 ±0.13
a
0.72 ±0.11
a
2.27 ±0.36
b
Vitamin C (lmol/g tissue) 83.04 ±16.33 41.16 ±5.87
a
33.36 ±6.39
a
89.14 ±18.74
b
Vitamin E (lmol/g tissue) 20.10 ±1.74 7.63 ±1.04
a
7.57 ±0.98
a
20.4 ±1.68
b
b-Carotene (lmol/g tissue) 1.21 ±0.08 0.65 ±0.10
a
0.59 ±0.08
a
1.10 ±0.10
b
a
p\0.001 versus control
b
p\0.001 versus depression group
156 J Nat Med (2013) 67:152–158
123

and duration of illness, and alterations in superoxide dis-
mutase and lipid peroxidation levels [3]. Increased oxida-
tive stress occurs in depression, as evidenced by defective
cerebral cortex antioxidant defenses in conjunction with
enhanced lipid peroxidation in patients [3] and experi-
mental animals [4,5,24]. In stress disorders, several routes
of damage are triggered, such as mitochondrial dysfunction
[1,6] and abnormalities of Ca
2?
influx [7] and the
phagocyte immune system [6]. These events make a sig-
nificant contribution towards the resultant pathophysiology
in brain characteristics in stress-induced depression.
Depression is also characterized by oxidative stress
production pathways such as mitochondrial dysfunction,
dysregulation of Ca
2?
homeostasis [6,7], disruption of
energy pathways, damage to neuronal precursor impair-
ment neurogenesis [8] and induction of signal events in
apoptotic cell death [6]. Lipid peroxidation levels such as
malondialdehyde is a major oxidative degradation product
of membrane unsaturated fatty acid and has been shown to
be biologically active with ROS properties [1,2]. In the
current study, CMS-induced depression enhanced cerebral
cortex lipid peroxidation levels in the animal system,
although fat-soluble antioxidants (vitamin A, vitamin E and
b-carotene) concentrations decreased. The brain has a high
content of oxidizable polyunsaturated fatty acids and pre-
vention of lipid peroxidation by antioxidants serves to
maintain membrane integrity by protecting membrane
phospholipids from damage, which is the result of a com-
plex cascade involving impairment of membrane-transport
protein function and cation channels that, in turn, mediates
membrane lipid peroxidation-induced disruption of neuro-
nal ion homeostasis [24,25].
Treatment of the CMS-induced depressed rats with rose
oil vapor effectively protected the rats against depression-
induced brain damage, as shown by increased antioxidant
concentrations and decreased lipid peroxidation levels
in the cerebral cortex. Rose oil showed antioxidant and
antinociceptive properties in the treatment of recurrent
aphthous stomatitis [26]. The destruction of membrane
phospholipids alters membrane viscosity and it is supposed
to influence several stages in biogenic amine function, such
as receptor density or function of serotonergic/catechola-
minergic receptors [3]. The oxidation of catecholamines
such as dopamine and serotonin by monoamine oxidase
(MAO) may result in an increased radical burden. The
inhibitory effects of serotonin on depression are very well
documented [27]; this effect has been attributed to a
serotonin-induced decrease in dopamine in the central
nervous system [28]. Selective serotonin reuptake inhibi-
tors (SSRIs) are effective in the treatment of depression;
the probable mechanism of these drugs is the enhancement
of net serotonergic transmission by blocking presynaptic
5-hydroxytryptamine (5-HT) uptake sites [29]. It is well
known that antioxidant flavonoids induce modulator effects
in SSRIs [10,30]. Rose oil contains flavonoids such as
geraniol and citronellol which demonstrated ROS scav-
enging activity in a model of auto-oxidation of rat cerebral
membranes [12]. Therefore, rose oil, with potential anti-
oxidant activity and regulator effects on SSRIs, may be of
value in depression. Furthermore, membrane lipid peroxi-
dation also modifies neurotransmitter release and uptake,
ion-channel activity, the function of ATPases and glucose
transporters, and the coupling of cell surface receptors to
GTP-binding proteins, to impair mitochondrial function
and promote a cascade of events that culminates in apop-
totic cell death [31,32]. Prevention of these potentially
damaging factors during CMS-induced lipid peroxidation
may possibly be a target of the antioxidant action of rose
oil, relevant to its therapeutic benefits.
This reported antidepressant-like effect of rose oil vapor
may be also dependent on different properties of this flower
oil, such as its neuromodulatory and antioxidant actions.
Studies report that in the central nervous system (particu-
larly in neurons) flavonoid is maintained at elevated con-
centrations and may act as a neuromodulator, facilitating
the release of some neurotransmitters and inhibiting neu-
rotransmitter binding to receptors, including responses
mediated by the glutamatergic system [12,33], which is
proposed to play a key role in the pathophysiology of
depression [13].
In conclusion, oxidative stress plays a role in the path-
ogenesis of CMS-induced depression in rat brain. The
beneficial effect of rose oil vapor on antioxidant vitamin
systems in CMS-induced depression was shown by
upregulation of vitamins A, vitamin C, vitamin E and
b-carotene concentrations in the cerebral cortex. The
results may be helpful to physicians and for the treatment
of depression with rose oil vapor, as well as to scientists for
clarification of the etiology of depression.
Acknowledgments The study was partially supported as a graduate
student project by TUBITAK, Ankara, Turkey.
Conflict of interest All authors reported that they have no conflicts
of interest.
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