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Rose geranium essential oil as a source of new and safe
anti-inflammatory drugs
Mohamed Nadjib Boukhatem
1,2
*, Abdelkrim Kameli
1
, Mohamed Amine
Ferhat
3
, Fairouz Saidi
2
and Maamar Mekarnia
4
1
Laboratoire Eco-Physiologie Ve
´
ge
´
tale, De
´
partement des Sciences Naturelles, Ecole Normale
Supe
´
rieure de Kouba, Alger, Algeria;
2
Laboratoire Biotechnologies Ve
´
ge
´
tales, De
´
partement de
Biologie, Universite
´
Saad Dahleb de Blida, Algeria;
3
Laboratoire de Recherche sur les Produits
Bioactifs et Valorisation de la Biomasse, Ecole Normale Supe
´
rieure de Kouba, Alger, Algeria;
4
Socie
´
te
´
Extral-Bio de Production des Huiles Essentielles et Cosme
´
tiques Bio, route de
Chiffa, Blida, Algeria
Background: Since the available anti-inflammatory drugs exert an extensive variety of side effects, the search
for new anti-inflammatory agents has been a priority of pharmaceutical industries.
Aims: The aim of the present study was to assess the anti-inflammatory activities of the essential oil of rose
geranium (RGEO).
Methods: The chemical composition of the RGEO was investigated by gas chromatography. The major
components were citronellol (29.13%), geraniol (12.62%), and citronellyl formate (8.06%). In the carrageenan-
induced paw edema, five different groups were established and RGEO was administered orally in three
different doses.
Results: RGEO (100 mg/kg) was able to significantly reduce the paw edema with a comparable effect to that
observed with diclofenac, the positive control. In addition, RGEO showed a potent anti-inflammatory
activity by topical treatment in the method of croton oil-induced ear edema. When the dose was 5 or 10 mlof
RGEO per ear, the inflammation was reduced by 73 and 88%, respectively. This is the first report to
demonstrate a significant anti-inflammatory activity of Algerian RGEO. In addition, histological analysis
confirmed that RGEO inhibited the inflammatory responses in the skin.
Conclusion: Our results indicate that RGEO may have significant potential for the development of novel anti-
inflammatory drugs with improved safety profile.
Keywords: essential oils; rose geranium; citronellol; anti-inflammatory effect; skin inflammation; histopathology; carrageenan;
croton
*Correspondence to: Mohamed Nadjib Boukhatem, Laboratoire Eco-Physiologie Ve´ge´tale, De´partement
des Sciences Naturelles, Ecole Normale Supe´rieure de Kouba, BP 92, 16050 Vieux-Kouba, Alger, Algeria,
Tel: 213557283091, Email: mn.boukhatem@yahoo.fr
Received: 2 August 2013; Revised: 16 September 2013; Accepted: 16 September 2013; Published: 7 October 2013
T
he World Health Organization projected that 80%
of people in emerging nations rely on medicinal
plants for primary health care needs. The cost of
acquiring synthetic drugs, their insufficient supplies,
the side effects associated with their uses, and the belief
that plants hold the cure for many disease conditions
(including inflammatory disorders) has led to a reawa-
kening of interest in the utilization of plants and plant
extracts in recent years. There is a need to expand
scientific investigation into medicinal plants especially
those claiming to have beneficial effects in serious
illnesses (1, 2).
Commercially available anti-inflammatory drugs exert a
wide range of side effects and are either too potent or too
weak. Consequently, the search for new anti-inflammatory
compounds has been a priority for the pharmaceutical
industry. Medicinal plants continue to be an important
source of new chemical substances with potential ther-
apeutic effects (3). Numerous natural products have been
tested in various animal models for the development of
new anti-inflammatory agents. Plant essential oils (EO)
are used as folk medicine against various kinds of inflam-
matory diseases. Some of them have also been scientifi-
cally shown to possess medicinal activities, including
(page number not for citation purpose)
æ
ORIGINAL ARTICLE
Libyan Journal of Medicine 2013. # 2013 Mohamed Nadjib Boukhatem et al. This is an Open Access article distributed under the terms of the Creative Commons
Attribution-Noncommercial 3.0 Unported License (http://creativecommons.org/licenses/by-nc/3.0/), permitting all non-commercial use, distribution, and reproduction in
any medium, provided the original work is properly cited.
1
Citation: Libyan Journal of Medicine 2013, 8: 22520 - http://dx.doi.org/10.3402/ljm.v8i0.22520
anti-inflammatory activities, in experimental systems
in vitro and in vivo (46).
In Algeria, the use of medicinal plants as anti-
inflammatory drugs is a common practice, although in
most cases the active principles of the plants are
unknown. Therefore, the study of plant species should
still be seen as a logical research strategy, in search for
new anti-inflammatory drugs. The variety of climatic and
geographic conditions in Algeria provides a rich source of
vegetation, comprising many species of plants (7).
Among these plants, rose geranium, which belongs to
the Geraniaceae family, has been widely used for its
antibacterial and antifungal actions. The RGEO is
extracted from the leaves and stems of the plant by steam
distillation. The RGEO is composed of various chemical
constituents such as linalool, citronellol, geraniol, and
their esters (8, 9). Rose geranium is one of the most
fragrant species and its EO is used in the perfumery and
cosmetics industry. It is also used as a flavoring agent and
as a spice. Further, the RGEO is non-toxic, non-irritant,
generally non-sensitizing, and it is not known to cause
any other side effects. The therapeutic properties of
RGEO include being an antidepressant, antiseptic and
wound-healing (vulnerary). RGEO may also be one of
the best oils for diverse dermatological problems such as
oily or congested skin, eczema, and dermatitis (10, 11).
Presently, there are no published scientific data to
validate the popular claims of anti-inflammatory activity
of the plant. The purpose of the present study was to
evaluate the anti-inflammatory activities of RGEO using
the carrageenan-induced paw edema and croton oil-
induced ear edema tests. In addition, we describe the
identification of the various constituents of RGEO by gas
chromatographymass spectrometry (GCMS).
Material and methods
Plant material and EO extraction
Rose-scented geranium was cultivated in the aromatic
garden of ‘Extral-Bio’ Company (Blida city, Algeria).
The aerial parts of the plant were collected in September
2012. Identification of the plant was confirmed by the
National Institute of Agronomy (Algiers, Algeria).
EO was obtained by steam distillation of fresh plant
material (Extral-Bio Company) in a stainless steel
distillation apparatus (alembic) for 3 h. The procedure
consists of passing water vapor at low pressure through a
tank containing the aromatic plant parts. The steam
captures the oil trapped in micro-pockets within the plant
tissue. The steam then passes through a cold-water
refrigerated serpentine to be condensed into liquid.
Upon exit, the collected liquid is a mixture of oil
and floral water, which are easily separated using a
Florentine vase. The RGEO thus obtained was dried
over anhydrous sodium sulfate, filtered, and stored at
48C until tested.
GC
MS analyses
GC analyses were performed using a Hewlett-Packard
(HP, Palo Alto, CA, USA) gas chromatograph equipped
with a flame ionization detector and HP5-MS capillary
column (30 m, 0.32 mm, 0.25 mm film thickness). The
oven temperature was programmed isothermally for 8
min at 458C and then 452408Cat28C/min for 15 min.
Injector and detector temperatures were 250 and 2808C,
respectively. Carrier gas was nitrogen at a flow rate of
1.2 ml/min in split mode 1:70 with an injection volume of
1 ml. The composition of RGEO was computed by the
normalization method from the GC peak areas.
GCMS analyses were performed using a Hewlett-
Packard GC system interfaced with a mass spectrometer
equipped with an HP5-MS capillary column (30 m, 0.32
mm, 0.25 mm film thicknesses). For GCMS detection,
electron ionization with ionization energy of 70 eV
was used. Helium was the carrier gas at a flow rate of
1.2 ml/min with an injection volume of 1 ml. Injector
and detector temperatures were set at 250 and 2808 C,
respectively.
Identification of the components of rose geranium
volatile oil were made by matching their recorded mass
spectra with the mass spectra data bank (Wiley 7N and
NIST 2002 libraries) and by comparing their reten-
tion indices (RIs) relative to a series of hydrocarbons
(C7C28) with literature values (12).
Experimental animals
Carrageenan-induced paw edema and croton oil-induced
ear edema was carried out on male Swiss mice (2530 g).
Male animals were purchased from the laboratory of
toxicology of Antibiotical Saidal Company (Medea,
Algeria) and were housed in groups of six per standard
cage, on a 12 h light/dark cycle with free access to food
and water. They were acclimatized to laboratory condi-
tions for at least 1 week before testing. The food was
withdrawn on the day before the experiment, but free
access to water was allowed. A minimum of six animals
was used in each group.
Determination of median lethal dose (LD
50
)
LD
50
of the RGEO was estimated in mice by using the
method of Hilan et al. (13). In a preliminary test, animals
in groups of three received 10, 100, or 1,000 mg/kg of
RGEO suspended in the vehicle (1% v/v Tween 80).
Animals were observed for 24 h for signs of toxicity and
number of deaths. The LD
50
was calculated as the
geometric mean of the dose that resulted in 100%
mortality and that which caused no deaths.
Mohamed Nadjib Boukhatem et al.
2
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Citation: Libyan Journal of Medicine 2013, 8: 22520 - http://dx.doi.org/10.3402/ljm.v8i0.22520
In vivo
anti-inflammatory activity assay
Carrageenan-induced paw edema in mice
The anti-inflammatory activity was evaluated by the
carrageenan-induced paw edema test (14). Paw edema
was induced by injecting 0.1 ml of the carrageenan 1%
suspension in isotonic saline (w/v) into the sub-plantar
region of the left hind paw of the mouse.
RGEO doses of 100, 200, or 400 mg/kg and vehicle
(0.2% Tween 80 in 0.9% NaCl) were administrated
(0.5 ml per animal) orally (per os) 30 min before injection
of the edematogenic agent to different groups of mice
for each treatment (n 6 per group). Diclofenac sodium
dissolved in 0.9% NaCl (50 mg/kg, oral) was used as
a reference drug. Paw thickness was measured before the
application of the inflammatory substance and every
30 min for 4 h after induction of inflammation. The
difference in footpad thickness was measured by a gauge
calliper (Facom, Paris, France).
Mean values of treated groups were compared with
those of control group (vehicle) and analyzed statistically.
The data obtained for the various groups are reported as
means9standard deviation (SD) and expressed in mm.
The percentage inhibition of the inflammatory reaction
was determined for each animal by comparison to the
controls and calculated by the formula:
I (%)
1
D(PV)
t
D(PV)
c
100
where I (%) percent inhibition of edema, (DPV)t the
change in paw volume in the treated mice, and (DPV)c
the change in paw volume in the control mice.
Croton oil-induced ear edema in mice
To estimate the anti-inflammatory activity of RGEO in
vivo, we used the acute inflammation model of croton oil-
induced mouse ear edema according to the method
described by Sosa et al. (15). An acetone solution of
croton oil (100 mg/15 ml) was carefully applied to the inner
surface of the left ear of each mouse. The right ear
remained untreated. Vehicle (2 ml/kg) and different doses
of the RGEO (200 or 400 ml/kg) were applied topically to
the left ear about 30 min before the croton oil treatment.
As a reference, we applied 1 mg/ear of the non-steroidal
anti-inflammatory drug, diclofenac sodium 1% gel
(Voltaren Emulgel, Novartis, France). For evaluation of
the activity, two different ways were followed:
1) The thickness of each ear was measured with a
gauge calliper 4 h after induction of inflammation.
The edema was expressed as the difference between
the right and left ears.
2) Four hours after induction of inflammation, the
mice were sacrificed and a tissue sample (a plug 5
mm in diameter) was removed with a Punch Biopsy
(LCH Medical products, Paris, France) from both
treated (left) and untreated (right) ears. The percen-
tage inhibition of the inflammation was determined
for each animal by comparison to the controls and
calculated by the following formula:
I (%)
1
D(WT)
t
D(WT)
c
100
where I (%)percent inhibition of edema, (DWT)t the
change in weight of ear tissue in the treated mice, and
(DWT)cthe change in weight of ear tissue in the control
mice.
Histopathological examination of mouse ear tissue
For morphological assessment of cutaneous inflamma-
tion, biopsies from control and treated ears of mice in
each treatment group were collected at the end of the
experiment. Samples were fixed in 4% formaldehyde and
decalcified. Fixed tissues were serially sliced at a thick-
ness of 5.0 mm using a microtome (Leica, Nussloch,
Germany). The sections were stained with Harry’s
Hematoxylin-Eosin. The tissues were examined by a light
microscope (Olympus) without blinding and graded for
edema as mild (), moderate (), or severe ().
The tissue samples were also examined for epidermal
hyperplasia and for inflammatory cell infiltration (mono-
nuclear and/or polymorphonuclear cells) in the dermis
inflammation phase.
Statistical analysis
Results of the paw edema of the mice are reported
as mean9SD. Comparison between groups was made
by one-way analysis of variance (ANOVA) followed
by Tukey’s post hoc multiple comparison test. Differences
with P B0.05 were considered statistically significant.
Statistical data analysis was determined by probit analysis
using XLStats 2013 Pros statistical software (Addinsoft,
Paris, France).
Results and discussion
Chemical composition of volatile oil
The EO was obtained by steam distillation in a stainless
steel alembic from fresh aerial part of rose-scented
geranium. The rose geranium oil obtained is a yellowish-
green liquid. It has a strong lemon-rose odor. The EO
was obtained with a yield of 0.15% (v/w). In a recent
study (16), it has been reported that a higher yield is
obtained during spring/summer (0.1%) than during
autumn/winter, with an average yield of 0.06%.
The volatile oil was analyzed by GC-MS. Qualitative
and quantitative studies of the oil volatile profiles are
listed in Table 1 in order of their retention indices.
In total, 20 compounds representing 83.5% of the EO
were identified. Citronellol (29.1%), geraniol (12.6%),
Anti-inflammatory activity of RGEO
Citation: Libyan Journal of Medicine 2013, 8: 22520 - http://dx.doi.org/10.3402/ljm.v8i0.22520 3
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citronellyl formate (8.1%), geranyl tiglate (7.1%), and
linalool (4.5%) were the major compounds in the oil,
with minor quantities of geranyl butyrate (2.0%) and
geranyl acetate (1.6%). Other constituents were found
in smaller amounts ( B2%). The rose geranium oil con-
sisted mainly of oxygenated monoterpenes (76.9%) and
oxygenated sesquiterpenes (3.3%).
The data presented here are consistent with previous
reports (9, 17), which demonstrated that rose geranium oils
are characterized by citronellol (22.032.9%) as the most
important component. However, our results diverge from
those published by other studies (18). Generally, the
observed differences in chemical composition of rose
geranium oils, when compared with those reported in
previous studies could be due to a number of factors,
including differences in climatic conditions and geogra-
phical locations, season at the time of collection, and
fertilization (17, 19). Previous reports revealed that
although the chemical composition of the RGEO differed
owing to the geographical origin, compounds such as
alcohols, ketones, esters, and mainly aldehydes have
consistently been recorded (8, 17).
Determination of median lethal dose (LD
50
)
The RGEO did not cause any mortality in the mice in doses
up to 1,000 mg/kg. Therefore, we suggest that oral LD
50
of
the tested volatile oil 1,000 mg/kg. Thus, this oil can be
considered as highly safe. Geranium oils were granted
GRAS status (Generally Recognized As Safe) and ap-
proved by the US Food and Drug Administration (FDA)
for food use (8).
Anti-inflammatory activity of EO
Carrageenan-induced paw edema in mice
The anti-inflammatory effect of EO was evaluated in
carrageenan-induced paw edema in mice, an animal
model widely employed to assess the anti-edematogenic
effect of natural products. Carrageenan is commonly
used as a phlogistic (inflammation-inducing) agent. The
resulting signs and symptoms of inflammation can be
measured as an increase in paw thickness due to the
edema.
The anti-inflammatory effect of the EO (100400 mg/kg)
was evaluated in the paw edema model (n 6 per group).
As shown in Table 2, the oral administration of EO at
doses of 100, 200 and 400 mg/kg resulted in 30, 38 and
73% reduction in paw edema, respectively. Furthermore,
the inhibition of paw edema resulting from a 100-mg/kg
EO dose was not significantly different from that of
diclofenac (50 mg/kg) (73.1% vs. 80.8%, P0.05). This
is the first demonstration that oral administration of
RGEO produces significant anti-inflammatory effects.
This evidence allows us to suggest that the anti-
inflammatory actions of RGEO are related to the
inhibition of one or more intracellular signaling pathways
involved in the effects of several inflammatory mediators.
A study carried out by Abe et al. (20) showed that the EO
of geranium suppressed the adherence response of human
neutrophils in vitro, and the intra-peritoneal administra-
tion of this oil to mice lowered induced neutrophil
recruitment into the peritoneal cavity.
Results from an investigation carried out on a number
of EOs established that a single intra-peritoneal injection
of RGEO clearly suppressed the carrageenan-induced
foot paw edema, and repeated administration of the oil
suppressed collagen-induced arthritis. These results re-
vealed that RGEO suppressed both acute and chronic
inflammatory responses in mice (21, 22).
Attempts have been made to identify the component(s)
responsible for such bioactivities (23). Some plant con-
stituents, particularly alcohol terpenoids (geraniol and
citronellol), have been reported to be useful in the manage-
ment of inflammatory processes (2326). Our results are
in agreement with those reported in the literature for
other EOs rich in monoterpenic alcohol and showing
Table 1
. Chemical profile of rose geranium essential oil
extracted by steam distillation
No. Compounds
a
RI Content %
1 a-Pinene 926 0.85
2 Linalool 1,125 4.52
3 cis-Rose oxide 1,129 0.92
4 trans-Rose oxide 1,131 0.36
5 Menthone 1,156 4.21
6 Citronellol 1,167 29.13
7 Geraniol 1,271 12.62
8 Citronellyl formate 1,275 8.06
9 Geranyl formate 1,300 3.46
10 Citronellyl acetate 1,342 0.43
11 a-Copaene 1,356 1.13
12 Geranyl acetate 1,366 1.58
13 Caryophellene 1,391 1.76
14 Citronellyl propanoate 1,444 0.66
15 a-Agarofuran 1,545 0.4
16 Geranyl N-butyrate 1,562 2.02
17 Phenylethyl tiglate 1,584 1.26
18 10-epi-gamma-Eudesmol 1,619 3.31
19 Citronellyl tiglate 1,667 0.48
20 Geranyl tiglate 1,700 7.14
Total identified 83.45
Oxygenated monoterpenes 76.85
Monoterpene hydrocarbons 1.13
Oxygenated sesquiterpenes 3.31
Sesquiterpene hydrocarbons 2.16
RIs (retention indices) were calculated on the HP-5 MS column
relative to C7-C28 n-alkanes.
a
Compounds listed in order of elution from an HP-5 MS column.
Mohamed Nadjib Boukhatem et al.
4
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Citation: Libyan Journal of Medicine 2013, 8: 22520 - http://dx.doi.org/10.3402/ljm.v8i0.22520
a very strong anti-inflammatory effect. Further, the
major constituents of the oil, namely citronellol, geraniol,
and linalool, were previously shown to possess anti-
inflammatory activities (20, 27). It has been reported
(24) that RGEO might be beneficial in the prevention/
treatment of neurodegenerative diseases in which inflam-
mation is part of the pathophysiology.
Croton oil-induced ear edema in mice
Since we found that RGEO has anti-inflammatory
activity in carrageenan-induced edema, we evaluated its
activity further in croton oil-induced ear edema to assess
the potential anti-inflammatory effect of topically applied
RGEO in vivo. The results showed dose-dependent
reduction of ear edema (Table 3). RGEO at doses of
200 or 400 ml/kg applied topically produced 73 and 88%
inhibition of ear edema, respectively. Diclofenac sodium
(40 mg/kg) produced 85% inhibition of croton oil-
induced inflammation, and this effect was not statistically
different from that observed with the maximum dose of
RGEO. To the best of our knowledge, this is the first
report to demonstrate that Algerian RGEO possesses
significant anti-inflammatory activity.
Increased skin thickness is often the first hallmark
of skin irritation and local inflammation. This parameter
is an indicator of a number of processes that occur dur-
ing skin inflammation, including increased vascular per-
meability, edema and swelling within the dermis, and
proliferation of epidermal keratinocytes. In our study,
treatment with EO (200 or 400 ml/kg) caused signifi-
cant decreases in edematous ear thickness of 0.19 and
0.15 mm, respectively.
In accordance with our results, Abe et al. (20) reported
that cutaneous application of EOs, especially RGEO, can
suppress inflammatory symptoms observed as reductions
in neutrophil accumulation and edema. More recently,
the efficacy of RGEO and geraniol was tested against
vaginal candidiasis as well as vaginal inflammation and
Candida growth form. The vaginal application of RGEO
successfully suppressed Candida cell growth in the vagina
and its local inflammation when combined with vaginal
washing, demonstrating the protective effect of RGEO
and its main monoterpene against vaginal inflammation
in mice (25).
Topical application of certain EOs, including RGEO,
is popular in the practice of aromatherapy and body
massage. Several of these oils are used to treat inflam-
matory conditions with neutrophil accumulation: rheu-
matoid arthritis, aphthous stomatitis, and bacterial or
fungal infections (20).
Histopathology analyses of ear tissue
We examined H&E-stained ear sections from croton oil
treated animals. Local application of croton oil resulted
in a marked increase in ear thickness with clear evidence
of epidermal hyperplasia, edema, and substantial inflam-
matory cell infiltration in the dermis with associated
connective tissue disturbance (Fig. 1C and D). Based on
the histological assessment, RGEO treatment reduced
edematous ear thickness and associated pathological
indicators to an extent comparable to the positive
control, diclofenac (Fig. 1B). The results of the histo-
pathology analysis were similar in carrageenan and
croton oil-induced edema methods. These results directly
Table 2
. Effect of rose geranium essential oil on carrageenan-induced paw edema in mice (n6)
Treatment Dose (mg/kg) Thickness of the left hind paw (mm), mean9SD Inhibition of paw edema (%)
Negative control 20 3.190.15
d
RGEO 400 390.05
c
30.76
RGEO 200 2.8890.11
b
38.46
RGEO 100 2.8190.17
a
73.07
Diclofenac 50 2.7690.12
a
80.76
Groups if mice were pretreated with vehicle (control group, 20 mg/kg, p.o., n6) diclofenac (50 mg/kg) or rose geranium essential oil at
doses of 100, 200 and 400 mg/Kg (p.o., n6/group) 30 min before carrageenan-induced paw edema. Means within the same column
followed by the same small letter are not significantly different (P 0.05) according to ANOVA one-way analysis followed by Tukey’s post
hoc multiple comparison test.
Table 3
. Topical application of rose geranium essential oil
prevents croton oil-induced ear edema in mice
Treatment Dose (ml/kg)
Weight edema
(mg) mean9SD Inhibition (%)
Negative Control 50 23.7597.67
c
RGEO 200 11.2593.30
b
73.52
RGEO 400 8.7592.21
a
88.23
Diclofenac 40 9.2593.09
a
85.29
Data are presented as mean (mm)9standard deviation (SD)
(n6 per group).
Means within the same column followed by the same small letter
are not significantly different (P0.05) according to ANOVA one-
way analysis followed by Tukey’s post hoc multiple comparison
test.
Anti-inflammatory activity of RGEO
Citation: Libyan Journal of Medicine 2013, 8: 22520 - http://dx.doi.org/10.3402/ljm.v8i0.22520 5
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illustrate the effects of RGEO within the target tissue,
providing further evidence that RGEO ameliorates cro-
ton oil-induced contact dermatitis. Our results are in
agreement with a study by Al-Reza et al. (28), whose
histological analysis revealed that Jujuba fruit oil inhi-
bited the inflammatory responses of skin inflammation.
Conclusions
RGEO is used as an antibacterial and antifungal
agent in folk medicine as well as a food preservative.
The results of our present study together with those
of other researchers give strong impetus to the considera-
tion of RGEO as a potentially useful anti-inflammatory
agent both for the prevention and treatment of acute
or chronic inflammatory skin diseases. In addition,
study of the major chemical constituents of RGEO might
accelerate the development of new, effective, and safe
anti-inflammatory drugs.
Conflict of interest and funding
The authors have not received any funding or benefits
from industry or elsewhere to conduct this study.
References
1. Taher YA. Antinociceptive activity of Mentha piperita leaf
aqueous extract in mice. Libyan J Med. 2012; 7: 16205.
2. Dub AM, Dugani AM. Antithrombotic effect of repeated doses
of the ethanolic extract of local olive (Olea europaea L.) leaves in
rabbits. Libyan J Med. 2013; 8: 20947.
3. Mahdi EJ. Aspirin and its related non-steroidal anti-inflamma-
tory drugs. Libyan J Med. 2013; 8: 21569.
4. Bakkali F, Averbeck S, Averbeck D, Idaomar M. Biological
effects of essential oils a review. Food Chem Toxicol. 2008; 46:
44675.
5. Chou ST, Lai CP, Lin CC, Shih Y. Study of the chemical
composition, antioxidant activity and anti-inflammatory activ-
ity of essential oil from Vetiveria zizanioides. Food Chem. 2012;
134: 2628.
6. Suntar I, Tumen I, Ustun O, Keles H, Akkol EK. Appraisal
on the wound healing and anti-inflammatory activities of
the essential oils obtained from the cones and needles of
Pinus species by in vivo and in vitro experimental models.
J Ethnopharmacol. 2012; 139: 53340.
7. Boukhatem MN, Saidi F, Hamaidi MS, Hakim Y, Mekarnia M.
Culture et exploitation industrielle du ge´ranium rosat (Pelargo-
nium graveolens) en Alge´rie: e´tat des lieux et perspectives.
Phytothe´rapie. 2011; 9: 3049.
8. Lis-Balchin M. Geranium and Pelargonium: the genera
Geranium and Pelargonium. London: CRC Press, Taylor &
Francis; 2002.
9. Boukhris M, Bouaziz M, Feki I, Jemai H, El Feki A, Sayadi S.
Hypoglycemic and antioxidant effects of leaf essential oil of
Fig. 1. Histopathology sections of mouse ear biopsies representing keratin, epidermal, dermal, and cartilage layers
(magnification xl00). Harry’s hematoxylin-eosin stained sections were scored as mild (), moderate (), and severe ()
for edema and substantial inflammatory mononuclear and/or polymorphonuclear cell infiltration in the dermis inflammation
phase. (A) no treatment; (B) rose geranium essential oil treatment: edema ( ); inflammatory cell infiltration (), inflammation
phase (9). (C) and (D) croton oil: edema (); inflammatory cell infiltration (), inflammation phase ().
Ke: keratin; Ep: epidermal layer; De: dermal layer; Mu: muscle; Ca: cartilage layer; Od: edema; Pc: polymorphonuclear
cell infiltration.
Mohamed Nadjib Boukhatem et al.
6
(page number not for citation purpose)
Citation: Libyan Journal of Medicine 2013, 8: 22520 - http://dx.doi.org/10.3402/ljm.v8i0.22520
Pelargonium graveolens L’He´r. Inalloxan induced diabetic rats.
Lipids Health Dis. 2012; 11: 110.
10. Lis-Balchin M, Hart S, Deans SG, Eaglesham E. Com-
parison of the pharmacological and antimicrobial action
of commercial plant essential oils. J Herbs Spices Med. 1996;
4: 6986.
11. Zore GB, Archana D, Thakre V, Rathod S, Karuppayil M.
Evaluation of anti-Candida potential of geranium oil constitu-
ents against clinical isolates of Candida albicans differentially
sensitive to fluconazole: inhibition of growth, dimorphism and
sensitization. Mycoses. 2010; 54: 99109.
12. Adams PP. Identification of essential oil components by
gas chromatography/quadrupole mass spectroscopy. Illinois:
Allured Publishing Corporation; 2004.
13. Hilan C, Bouaoun D, Aoun J, Sfeir R, Garabeth F. Antimicro-
bial properties and toxicity by LD50 determination of an
essential oil of Prangosa sperula Boissier. Phytothe´rapie. 2009;
7: 814.
14. Winter CA, Risley EA, Nuss GW. Carrageenin induced edema
in hind paw of the rat as an assay for anti-inflammatory drugs.
Proc Soc Exp Biol Med. 1962; 1: 5447.
15. Sosa S, Altinier G, Politi M, Braca A, Morelli I, Della Loggia R.
Extracts and constituents of Lavandula multifida with topical
anti-inflammatory activity. Phytomedicine. 2005; 12: 2717.
16. Mosta NM, Puffy S, Martin SJ. Plant shoot age and tempera-
ture effects on essential oil yield and oil composition of rose-
scented geranium (Pelargonium sp.) grown in South Africa.
J Essent Oil Res. 2006; 18: 10610.
17. Rajeswara Rao BR, Kaul PN, Syamasundar KV, Ramesh S.
Water soluble fractions of rose-scented geranium (Pelargonium
species) essential oil. Bioressour Technol. 2002; 84: 2436.
18. Juliani HR, Koroch A, Simon JE, Hitimana N, Daka A,
Ranarivelo L, et al. Quality of geranium oils (Pelargonium
species): case studies in Southern and Eastern Africa. J Essent
Oil Res. 2006; 18: 11621.
19. Verma RS, Rahman LU, Verma RK, Chauhan A, Singh A.
Essential oil composition of Pelargonium graveolens L’Her ex
Ait. cultivars harvested in different seasons. J Essent Oil Res.
2013; 6: 18.
20. Abe S, Maruyama N, Hayama K, Inouye S, Oshima H,
Yamaguchi H. Suppression of neutrophil recruitment in mice
by geranium essential oil. Mediat Inflamm. 2004; 13: 214.
21. Maruyama N, Sekimoto Y, Ishibashi H, Inouye S, Oshima H,
Yamaguchi H, et al. Suppression of neutrophil accumulation
in mice by cutaneous application of geranium essential oil.
J Inflamm. 2005; 2: 111.
22. Maruyama N, Ishibashi H, Hu W, Morofuji S, Inouye S,
Yamaguchi H, et al. Suppression of carrageenan-and collagen
II-induced inflammation in mice by geranium oil. Mediators
Inflamm. 2006; 2006: 62537.
23. Su YW, Chao SH, Lee MH, Ou TY, Tsai YC. Inhibitory effects
of citronellol andgeraniol on nitric oxide and prostaglandin E2
production in macrophages. Plant Med. 2010; 76: 166671.
24. Elmann A, Mordechay S, Rindner M, Ravid U. Anti-
neuroinflammatory effects of geranium oil in microglial cells.
J Funct Foods. 2010; 2: 1722.
25. Maruyama N, Takizawa T, Ishibashi H. Protective activity of
geranium oil and its component, geraniol, in combination with
vaginal washing against vaginal candidiasis in mice. Biol Pharm
Bull. 2008; 31: 15016.
26. Pe´rez GS, Zavala SM, Arias GL, Ramos LM. Anti-
inflammatory activity of some essential oils. J Essent Oil Res.
2011; 23: 3844.
27. Chen W, Viljoen AM. Geraniol a review of a commercially
important fragrance material. S Afr J Bot. 2010; 76: 64351.
28. Al-Reza SM, Yoon JI, Kim HJ, Kim JS, Kang SC. Anti-
inflammatory activity of seed essential oil from Zizyphus jujuba.
Food Chem Toxicol. 2010; 48: 63943.
Anti-inflammatory activity of RGEO
Citation: Libyan Journal of Medicine 2013, 8: 22520 - http://dx.doi.org/10.3402/ljm.v8i0.22520 7
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