Send Ord ers for R eprints to firstname.lastname@example.org
Current Pharmaceutical Biotechnology, 2014, 15, 173-181 173
α-(-)-bisabolol Reduces Pro-inflammatory Cytokine Production and
Ameliorates Skin Inflammation
Anil K. Maurya, Monika Singh, Vijaya Dubey, Suchita Srivastava, Suaib Luqman and
Dnyaneshwar U. Bawankule*
Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow-226015,
Abstract: α-(-)-bisabolol is a natural monocyclic sesquiterpene present in the essential oil has generated considerable in-
terest in the chemical and pharmaceutical industries and currently in use in various formulations, mainly in cosmetics.
This study was undertaken to evaluate its therapeutic profile against skin inflammation using in-vitro, in-vivo and in-silico
assays. Lipopolysachharide (LPS) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced production of pro-
inflammatory cytokines (TNF-α and IL-6) in macrophage cells as well as in TPA-induced skin inflammation in mice was
significantly inhibited by α-(-)-bisabolol. TPA-induced ear thickness, ear weight and lipid peroxidation and histopa-
thological damage in the ear tissue were also significantly inhibited by topical application of α-(-)-bisabolol in a dose de-
pendent manner. In-vitro and in-vivo toxicity profiles indicate that it is safe for topical application on skin. Molecular
docking study also revealed its strong binding affinity to the active site of the pro-inflammatory proteins. These findings
suggested that α-(-)-bisabolol may be a useful therapeutic candidate for the treatment of skin inflammation.
Keywords: α-(-)-bisabolol, anti-inflammatory, macrophage, 12-O-tetradecanoylphorbol-13-acetate, mice, LPS.
Inflammation is the common biological reaction to a va-
riety of stimuli and local injury . It is a complex patho-
physiological process mediated by a variety of signaling
molecules produced by activated leukocytes, which bring
edema formation as a result of extravasation of fluid and
cells at the inflammatory site . Skin plays a central role in
host defenses and regulation of defense mechanism is vital
for immunity . Skin diseases linked with inflammation are
the most common problem in dermatology. They are in
many forms, from occasional rashes accompanied by skin
itching and redness, to chronic conditions such as dermatitis,
rosacea, seborrheic dermatitis, and psoriasis . Pathogene-
sis of psoriasis is not fully understood. Several researches
have demonstrated that keratinocytes are known to partici-
pate in inflammatory reactions by producing a variety of
inflammatory cytokines. Psoriasis is a non-contagious skin
disorder which has a physical impact includes itching to the
skin, pain and restricted motion in their joints, but also ad-
versely affects the psychological feelings of the sufferers
leading to anxiety, anger, embarrassment, low self-esteem
and even depression . Experimental evidences has shown
that exposure of skin to 12-O-tetradecanoylphorbol-13-
acetate (TPA) induces a pleiotropic tissue response encom-
passing a strong inflammatory reaction similar to that ob-
served in skin diseases .
*Address correspondence to this author at the Molecular Bioprospection
Department, CSIR-Central Institute of Medicinal and Aromatic Plants
(CSIR-CIMAP), Lucknow, India; Tel: +91-522-2718646;
Fax: +91-522-2342666; E-mail: email@example.com
α-(-)-bisabolol is an unsaturated, optically active ses-
quiterpene alcohol found as a major component of essential
oil of chamomile. Chamomile, one of the most recognized
herbs to mankind which has been used traditionally as an
anti-inflammatory, antispasmodic, carminative, mild astrin-
gent and healing medicine . Pharmacological study re-
vealed that α-(-)-bisabolol has anti-microbial , nematicidal
and gastroprotective effect against ethanol and indometha-
cin-induced ulcer in mice , and skin inflammation .
In this study, we examined the impact of α-(-)-bisabolol
on the production of pro-inflammatory cytokine in macro-
phage cells stimulated with lipopolysaccharide (LPS) and
12-O-tetradecanoylphorbol-13-acetate (TPA) as an in-vitro
study. We have further validated our finding in in-vivo sys-
tem in TPA-induced skin inflammation in mice as well as
molecular docking interaction study with pro-inflammatory
cytokines. We also examined the safety study (in-vitro and
in-vivo) of α-(-)-bisabolol. Our results reveal that α-(-)-
bisabolol reduces pro-inflammatory cytokine production and
ameliorates skin inflammation without any toxic effect.
2. MATERIALS AND METHODS
α-(-)-bisabolol, RPMI 1640 medium, dexamethasone and
12-o-tetradecanoylphorbol-13-acetate (TPA) were purchased
from Sigma- Aldrich USA. TNF-α and IL-6 were from BD
Biosciences, USA, and fetal bovine serum was from Gibco,
18-/14 $58.00+.00 © 2014 Bentham Science Publishers
174 Current Pharmaceutical Biotechnology, 2014, Vol. 15, No. 2 Maurya et al.
2.2. In-vitro Study
2.2.1. Primary Cell Culture
Isolation of peritoneal macrophage cells was done as
described previously . In brief, the macrophage cells
were isolated from the peritoneal cavities of female Swiss
albino mice after an intra-peritoneal injection of 1.0 mL of
1% peptone (BD Biosciences, USA) 3 days before harvest-
ing. Mice were euthanized by cervical dislocation under
ether anesthesia and peritoneal macrophage cells were ob-
tained by intra-peritoneal injection of phosphate buffer saline
(PBS). Cell viability was determined by trypan blue exclu-
sion and the concentration of 0.5 × 106 live cells/mL was
used for the study. The cells were suspended in RPMI 1640
medium (Sigma–Aldrich, USA) containing 10% heat-
inactivated fetal bovine serum (Gibco, USA), 100 U/mL of
penicillin and 100 µg/mL of streptomycin and incubated in a
culture plate (Nunc, Germany) at 370 C in 5% CO2 in an in-
cubator. Non-adherent cells were removed after 4 h by re-
moving the culture media and the adherent cells were re-
suspended in the media without antibiotic.
2.2.2. Cell Toxicity
Effect of α-(-)-bisabolol on cell cytotoxicity was carried
out in peritoneal macrophage cells using 3-(4, 5-
dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay
as described by Sharma et al., (2012). Peritoneal macrophage
cells (0.5 x 106 cells/well) isolated from mice were sus-
pended in RPMI 1640 medium (Sigma, USA) containing
10% heat-inactivated fetal bovine serum (Gibco, USA) and
incubated in a 96 well plate at 37ºC in 5% CO2 in an incuba-
tor and left overnight to get attached. Cells treated with 1%
DMSO served as a vehicle control for cell cytotoxicity study.
α-(-)-bisabolol was dissolved in DMSO. Cells were treated
(1, 3, 10, 30 and 100µg/mL) and incubated for 24 h at 37ºC
in 5% CO2. After incubation 20 μL of MTT solution
(5mg/mL in PBS) were added to each well and left for 4 h
followed by media removal and cell solubilization in DMSO
(100µL) for 10 min. Absorbance was measured at 570nm
using micro-plate reader (Spectramax; Molecular Devices,
USA). The amount of color produced is directly proportional
to the number of viable cells. Cytotoxicity was calculated as
follows: Percentage (%) of survival = (mean experimental
absorbance/mean control absorbance×100).
2.2.3. Quantification of Pro-inflammatory Cytokines
Culture macrophage cells were pre-treated with 1, 3 and
10 µg/mL of α-(-)-bisabolol and/or dexamethasone, a stan-
dard anti-inflammatory drug (Sigma Aldrich, USA) at
1µg/mL for 30 min. The in-vitro anti-inflammatory study
was performed in two sets. The cells were stimulated with
LPS (0.5µg/mL) and TPA (10µg/mL), respectively for 24 h,
and collected supernatants were immediately frozen at
−80oC. Pro-inflammatory mediators (TNF-α and IL-6) were
quantified from supernatant using ELISA method according
to the manufacturer’s instructions (BD Biosciences, USA).
The values of TNF-α, and IL-6 were expressed as pg/mL.
2.3. In-vivo Study
2.3.1. Experimental Animals
Female BALB/c mice (25–35g), housed at 22±2oC (60–
80% humidity) under a 12h light/12h dark cycle and with
access to food and water ad libitum, were used for this study.
The animals were allowed to adapt to the laboratory for a
week before testing. Experiments were performed according
to the ethical guidelines suggested by the Institutional Ani-
mal Ethics Committee (IAEC) and Committee for the Pur-
pose of Control and Supervision of Experiments on Animals
(CPCSEA), Government of India.
2.3.2. TPA-induced Mouse Ear Inflammation
Topical inflammation was induced in right ears of female
BALB/c mice by the topical application of TPA (2.5μg) dis-
solved in acetone (20μL). A volume of 10μL was delivered
to both the inner and outer surface of the ear. α-(-)-bisabolol
was diluted in acetone in the ratio of 0.1%, 0.3% and 1.0%
for topical anti-inflammatory study. α-(-)-bisabolol was ap-
plied to the right ears at the dose of 20μL/ear/time 30 min
after TPA administration. For comparison, two other groups
were treated with TPA (vehicle control and dexamethasone
2.3.3. Ear Edema and Tissue Weight Measurement
Ear ed ema was expressed as the increase in ear thickness
due to the inflammatory challenge. Ear thickness was meas-
ured before and after induction of the inflammatory response
by using an electronic digital micrometer (Aerospace In-
struments). At 6 h, when TPA-induced inflammation was
maximal, animals were euth anized by ether anesthesia and
1cm diameter punch of ear tissue wet weight was taken for
quantification of inflammatory mediators from tissue ho-
mogenate. These tissues were quickly placed in a beaker
containing ice-cold Tris- HCl buffer (pH 7.4) and minced
into small pieces on ice and homogenized immediately in
tissue homogenizer (Pro Scientific Inc, USA). The ho-
mogenate (5%) was frozen and stored at -80°C till it’s used
for biochemical estimation. The tissue homogenate was
processed for the estimation of malondialdehyde (MDA) and
2.3.4. Quantification of Lipid Peroxidation and Inflamma-
Quantification of lipid peroxidation was performed fol-
lowing the thiobarbituric acid (TBA) test. The amount of
MDA formed was quantitated by reaction with TBA and
used as an index of lipid peroxidation. The results were
expressed as µM MDA/mL tissue homogenate. Pro-
inflammatory cytokines (TNF-α and IL-6) were quantified
from tissue homogenate using commercially available mouse
specific enzyme immune assay (EIA) k its (BD Biosciences,
USA) as per the manufactures instructions.
After fixation of the ear tissues in 10% buffered formalin.
The tissues were rinsed with water, dehydrated with graded
concentration of ethanol and embedded in paraffin wax. The
samples were sectioned into 4-5 μm thickness and mounted
α-(-)-bisabolol Reduces Pro-inflammatory Cytokine Production Current Pharmaceutical Biotechnology, 2014, Vol. 15, No. 2 175
on glass slides and stained with hematoxylin and eosin (H&E
stain). A representative area was selected for qualitative light
microscopic analysis (200× magnification).
2.3.6. Primary Skin Irritation
Primary skin irritation study was performed for the topi-
cal application of α-(-)-bisabolol in four healthy New Zea-
land white rabbits (1500±250g body weight) as per the ap-
proved protocol by the Institutional Animal Ethical Commit-
tee of CSIR-CIMAP, Lucknow, India.
α-(-)-bisabolol @ 1% was applied to the previously
shaved skin of rabbits on one inch square area. Normal saline
(1%) was applied as vehicle control at opposite side of skin.
Observations were made at 1, 4, 24, 48 and 72 h to assess
individual erythema and edema. The primary irritation index
(PII) was determined using the following formula; PII = Test
site score – Control site score .
2.4. In-silico Study
2.4.1. Molecular Docking
The methodology utilized was previously described 
for automated docking of flexible ligands with receptor using
Lamarckian genetic algorithm. The binding interaction of
α-(-)-bisabolol and dexamethasone was calculated by using
the freely available software AUTODOCK TOOLS 1.5.4.
The 3D structure of receptor (protein) was obtained from
protein data bank (http://www.rcsb.org/pdb/home/home.do).
The 3D structure of ligand (molecule) in sdf format was ob-
tained from Pubchem (http://pubchem.ncbi.nlm.nih.gov/)
and converted into 3D PDB structure by Open Babel Soft-
ware 2.0.2. Grid parameter file of the dimensions (60 X 60 X
60) for the receptor was prepared. Docking parameter file
based on Lamarckian genetic algorithm was prepared.
Command for docking was given on cygwin terminal (pro-
vides Unix/Linux like environment and command interface
for windows) supported by autogrid4 and autodock4 exten-
sion files. Results of the full run of a docking experiment
were collected from the dlg file obtained on full completion
of the single run of the software. The docking score in terms
of binding energy and inhibition constant values were ob-
tained for the ligand and receptor interaction. Usually, more
negative binding energy (Kcal/mol) is considered good for
effective interaction of the ligand with the receptor.
2.5. Statistical Analysis
Results are presented as th e Mean±SE and analysed using
GraphPad Prism 4. The one-way ANOVA followed by
Tukey’s multiple comparison test was used to assess the sta-
tistical significance of vehicle vs treatment groups. Probabil-
ity (P) values less than 0.05 were considered significant.
3.1. In-vitro Study
3.1.1. Cell Toxicity
Effect of α-(-)-bisabolol on cell viability in peritoneal
macrophage cells was evaluated using MTT assay. The sig-
nificant change in percent cell survival was not observed at
any concentration of the treatment when compared with
normal cells. Results are summarized in (Fig. 1).
3.1.2. Quantification of Pro-inflammatory Cytokines
Production of pro-inflammatory cytokines was signifi-
cantly decreased (p < 0.05) in α-(-)-bisabolol treated cells in
LPS as well as TPA-induced inflammation in macrophage
cells in a dose dependent manner. Representative results ar e
depicted in (Fig. 2).
Table 1. Grading score for primary skin irritation test in rabbit.
Skin Irritation score Score
• No erythema
• Very slight erythema (barely perceptible)
• Well defines erythema
• Moderate erythema
• Severe erythema (beet redness)
• No edema
• Very slight edema (barely perceptible)
• Well defined edema (edges of area well defined by definite raising)
• Moderate edema (raised approximately 1 mm)
• Severe edema (raised more than 1 mm and extending beyond exposure area)
176 Current Pharmaceutical Biotechnology, 2014, Vol. 15, No. 2 Maurya et al.
Fig. (2). % Cell viability of α-(-)-bisabolol using MTT assay.
3.2. In-vivo Study
3.2.1. Ear Thickness and Ear Weight
Ear edema was observed in all TPA-treated animals at 6h
after treatment. Mice treated with vehicle (Acetone), initial
ear thickness was 0.22mm. Ear thickness increased to
0.47mm by 6 h after TPA treatment. α -(-)-bisabolol treated
experimental mice showed significant reduction of ear
edema when compared with vehicle treated mice. α -(-)-
bisabolol and dexamethasone treatment exhibited the signifi-
cant reduction in ear edema when comp ared with the mice
treated with vehicle (Fig. 3 A). Ear punch biopsy weight at
6h was significantly lower in α-(-)-bisabolol and dexametha-
sone treated mice groups compared to the TPA treated vehi-
cle control group (Fig. 3 B).
3.2.2. Pro-inflammatory Cytokines
The mice treated with vehicle in TPA-induced ear in-
flammation showed the significant (P<0.05) increase in pro-
inflammatory cytokines (TNF-α and IL-6) production when
compared with the normal mice treated with vehicle,
whereas α -(-)-bisabolol showed the inhibition of pro-
inflammatory cytokines levels. Significant (P<0.05) inhibi-
tion of pro-inflammatory cytokines production was observed
in 1.0% α -(-)-bisabolol and dexamethasone treated mice
3.2.3. Lipid Peroxidation
MDA was measured from the homogenate of ear punch
biopsies taken 6h after TPA administration as an index
of lipid peroxidation. The ears treated with 0.3%, 1.0%
α-(-)-bisabolol and dexamethasone doses had significantly
reduced the MDA activity (Fig. 5).
Ear sections obtained from vehicle treated mice resulted
in a marked increase in ear thickness with clear evidence of
edema, and inflammatory cell (infiltrated leukocyte) infiltra-
tion in the dermis with accompanying connective tissue dis-
ruption. By histological comparison, the ears treated with
α-(-)-bisabolol 1.0% and dexamethasone doses had shown
significant changes in ear section (Fig. 6).
Fig. (1). Dose-response effect of α -(-)-bisabolol on LPS and TPA induced inflammation in Macrophages. (A) LPS induced (B) TPA in-
duced. Results are Mean±SEM; n= 4; * P<0.05 (Vehicle vs Treatment).
α-(-)-bisabolol Reduces Pro-inflammatory Cytokine Production Current Pharmaceutical Biotechnology, 2014, Vol. 15, No. 2 177
Fig. (3). Dose-response effect of α-(-)-bisabolol on TPA-induced inflammatory ear swelling in BALB/c mice (A) Change in ear thickness (B)
Ear weight. Results are Mean±SEM; n=8; * P<0.05 (Vehicle vs Treatment).
Fig. (4). Effect of α-(-)-bisabolol on inflammatory mediators on TPA-induced ear inflammation in BALB/c mice (A) Ear homogenateTNF-α
(B) Ear homogenate IL-6. Data are expressed as Mean±SEM; n= 4; * P<0.05 (Vehicle vs Treatment).
178 Current Pharmaceutical Biotechnology, 2014, Vol. 15, No. 2 Maurya et al.
Fig. (5). Dose-response effect of α-(-)-bisabolol on TPA-induced oxidative stress mediators quantification from ear tissue homogenate, MDA
formation expressed in μM/ml tissue homogenate. Results are Mean±SEM; n= 4; * P<0.05 (Vehicle vs Treatment).
Fig. (6). Representative photomicrograph of transverse sections of mice ears sensitized with topical application of TPA stained with hema-
toxylin–eosin and examined under light microscopy (magnification: 200×). Treatments: (A) Normal (B) Vehicle (C) α-(-)-bisabolol 0.1%,
(D) α-(-)-bisabolol 0.3%, (E) α-(-)-bisabolol 1% and (F) Dexamethasone 0.1 % . Arrows indicate the epidermis and arrowheads indicate the
inflammatory cells (infiltrated leukocyte). The shown sections are representative of five animals per group.
3.2.5. Primary Skin Irritation
Skin Irritation test was conducted to determine the
primary skin irritation on rabbit skin. 72 hr after the applica-
tion of α -(-)-bisabolol on rabbit skin. Significant erythema
and odema formation were observed in α-(-)-bisabolol treat-
ment site compared to vehicle treated site (Table 2). Pigmen-
tation, blood oozing and rough skin were also not observed
in both the control and treatment site. According to Federal
Hazardous Substances Act (FHSA) regulations, a material
with a PII of less than 5.00 is generally not considered a pri-
mary irritant to the skin. The PII result concluded that the
application of α-(-)-bisabolol is not irritant to the rabbit skin.
3.3. Molecular Docking
Molecular interaction study revealed that α -(-)-bisabolol
and dexamethasone when docked with pro-inflammatory
targets (IL-6 and TNF-α) show good docking scores in terms
of Binding energy and Inhibition constant (Ki) values. Thus
both the ligands possess high affinity for the receptors
(Table 3). Several previous reports also concluded that the
α-(-)-bisabolol Reduces Pro-inflammatory Cytokine Production Current Pharmaceutical Biotechnology, 2014, Vol. 15, No. 2 179
molecules having high binding affinity with targeted protein
exhibited therapeutic efficacy.
Treatment of most inflammatory skin diseases are domi-
nated by topical or oral corticosteroids. These are typically
used for only short periods of time because they exert some
negative side effects on skin, including immunosuppression,
hyperglycemia etc .
α-(-)-bisabolol is a natural monocyclic sesquiterpene pre-
sent in the essential oil of different plants, including chamo-
mile flowers. α-(-)-bisabolol has generated considerable eco-
nomic interest because it possesses a delicate floral odour
and has been shown to have several pharmacological activi-
ties . Pharmaceutical industries currently use α-(-)-
bisabolol in various formulations, mainly in cosmetics as
aftershave lotions, moisturisers, emulsions for sensitive skin
and creams for children. In this study, we examined the im-
pact of α-(-)-bisabolol on the production of pro-inflammatory
cytokine in macrophage cells stimulated with lipopolysac-
charide (LPS) and 12-O-tetradecanoylphorbol-13-acetate
(TPA) as an in-vitro study. We have further validated our
finding in in-vivo system in TPA-induced skin inflammation
in mice as well as molecular docking interaction study with
pro-inflammatory cytokines as well as its safety profile.
In-vitro results demonstrate that the production of pro-
inflammatory cytokines was significantly decreased (p <
0.05) in α-(-)-bisabolol treated cells in LPS as well as TPA-
induced inflammation in macrophage in dose dependant
manner without any cytotoxic effect. Our findings are similar
with the previous observation that α-(-)-bisabolol can inhibit
the production of pro-inflammatory cytokines . The con-
trol of overproduction of the inflammatory mediators may
greatly facilitate the treatment of many inflammation linked
To substantiate its efficacy to make it best suited for
clinical indications that can be treated with topical therapeu-
tics, we examined its therapeutic efficacy in TPA-induced
skin inflammation in mouse model. The induction of ear skin
inflammation in mice by TPA represents a promising animal
model for elucidating the mechanism of clinical dysfunctio n
and for evaluating the efficacy of topical anti-inflammatory
agents [17, 18]. The results of the study exhibits that the
topical application of TPA increased the ear thickness and
ear weight significantly when compared to the normal mice
treated with acetone alone. Increased skin thickening is often
the first hallmark of skin irritation and local inflammation.
This parameter is indicative of a number of processes that
occur during skin inflammation, including increased vascular
permeability, edema and swelling within the dermis, and
proliferation of the epidermal keratinocytes. The mice
treated with α-(-)-bisabolol exhibited the reduction of oxida-
tive stress and pro-inflammatory markers level . An im-
balance between oxidants and antioxidants can lead to oxida-
tive stress, characterized by escalating cell damage .
Oxidative stress is characterized by increased lipid peroxida-
tion and/or altered non enzymatic and enzymatic antioxidant
systems . Pro-inflammatory cytokines (TNF-α and IL-6)
in ear tissue homogenate was significantly increased in TPA
challenged vehicle treated mice when compared with normal
mice. Topical application of α-(-)-bisabolol is able to reduce
(p<0.05) the production of pro-inflammatory cytokines
(TNF-α and IL-6) in dose dependant manner when compared
with vehicle treated mice. It is widely recognized that the
secretions of cytokines by keratinocytes in response to injury
Table 2. Effects of α-(-)-bisabolol on primary skin irritation in rabbit.
Hours After treatment
Control site Treatment Site
1 0 0 No
4 0.25 0.75 No
24 0 0.75 No
48 0 0 No
72 0 0 No
Table 3. Binding affinity score of α-(-)-bisabolol w ith resp ect to th e inflammatory targets; IL-6 and TNF-α.
Ligand Details Receptors
Mice Interleukin 6 (2L3Y) Tumor Necrosis Factor- α
Name CID Code
BE Ki BE Ki
α-(-)-bisabolol 1549992 -5.7 65.82 -4.73 341.75
Dexamethasone 5743 -5.88 48.56 -6.31 28.83
BE: Binding energy expressed in terms of Kcal/mol; Inhibition constant (Ki): Expressed in μM.
180 Current Pharmaceutical Biotechnology, 2014, Vol. 15, No. 2 Maurya et al.
are key mediators of the cutaneous inflammatory response
. In this study, it has been clearly demonstrated topical
treatment with α-(-)-bisabolol inhibits the secretion of TNF-α
and IL-6. Primary skin irritation study in rabbits revealed
that it is safe for topical application on skin.
In-vitro and in-vivo anti-inflammatory profile of α -(-)-
bisabolol was further confirmed by molecular docking study.
The aim of the molecular interaction study was to explore
the interaction of α -(-)-bisabolol with pro-inflammatory cy-
tokine receptors. The interaction study was compared with
dexamethasone, a standard steroidal anti-inflammatory drug.
Molecular interaction study of α -(-)-bisabolol with pro-
inflammatory cytokines through docking showed high bind-
ing affinity i.e. low docking energy with pro-inflammatory
cytokines. Several previous reports also conclude that the
molecules having high binding affinity with targeted protein
exhibited therapeutic efficacy .
The present work conclude through in-vitro, in-vivo and
in-silico study that α-(-)-bisabolol reduces pro-inflammatory
cytokine production and ameliorates skin inflammation. This
study confirms the suitability of α -(-)-bisabolol as a candi-
date for further studies to obtain a suitable prototype drug for
chronic skin inflammatory disorders.
CONFLICT OF INTEREST
The authors confirm that this article content has no con-
flict of interest.
The study was financially supported by CSIR-CIMAP
under OLP-17 project. The authors are grateful to the Direc-
tor of the institute for kind support during the progress of the
 Sosa, S.; Balick, M.J.; Arvigo, R.; Esposito, R.G.; Pizza, C.; Alti-
nier, G.; Tubaro, A. Screening of the topical anti-inflammatory ac-
tivity of some Central American plants. J. Ethnopharmacol., 2002,
 Gokhle, A.B.; Damre, A.S.; Kulkarni, K.R.; Saraf, M.N. Prelimi-
nary evaluation of anti-in flammatory and anti-arthiritic activity of
S. lappa, A. speciosa and A. aspera. Phytomedicine, 2002, 9(5).
 DeVry, G.C.; Valdez, M.; Lazarov, M.; Muhr, E.; Buelow, R.; Fong,
T.; Iye, S. Topical application of a novel immunomodulatory pe ptide,
RDP58, reduces skin inflammation in the phorbol ester-induced der-
matitis model. J. Investigat. Dermatol., 2005, 125, 473-481.
 Kupper, T.S.; Fuhlbrigge, R.C. Immune surveillance in the skin:
mechanisms and clinical consequences. Nat. Rev. Immunol., 2004,
 Kock, A.; Schwarz, T.; Kirnbauer, R.;Urbanski, A.; Perry, P.; An-
sel, J.C.; Luger, T.A. Human keratinocytes are a source for tumor
necrosis factor alpha: evidence for synthesis and release upon
stimulation with endotoxin or ultraviolet light. J. Experiment. Med.,
1990, 172, 1609-1614.
 Hvid, H., Teige, I., Kvist, P.H., Svensson, L., Kemp, K. TPA in-
duction leads to a Th17-like response in transgenic K14/VEGF
mice: a novel in vivo screening model of psoriasis. Int. Immunol.,
2008, 20, 1097-1106.
 Reynolds, J.E.F. (Ed.). Martindale, the Extra Pharmacopoeia. The
Pharmaceutical Press, London, 1996.
 Forrer, M.; Kulik, E.M.; Filippi, A.; Waltimo, T . The antimicro bial
activity of alpha-bisabolol and tea tree oil against Solobacterium
moorei, a Gram-positive bacterium associated with halitosis. Arch.
Oral Biol., 2013, 58(1), 10-6.
 Rocha, N.F.; Oliveira, G.V.; Araújo, F.Y.; Rios, E.R.; Carvalho,
A.M.; Vasconcelos, L.F.; Macêdo, D.S.; Soares, P.M.; Sousa, D.P.;
Sousa, F.C. (-)-a-Bisabolol-induced gastroprotection is associated
with reduction in lipid peroxidation, superoxide dismutase activity
and neutrophil migration. Eur. J. Pharm. Sci., 2011, 44(4), 455-61.
 Leitea, O.G.; Leitea, L.H.I.; Sampaioa, R.S.; Ararunaa, M.K.;
Menezesa, I.R.; Costaa, J.G.; Camposb, A.R. (−)-α-Bisabolol at-
Fig. (7). α-(-)-bisabolol and dexamethasone docked on target protein; TNF-α (1TNF), IL-6 (1ALU).
α-(-)-bisabolol Reduces Pro-inflammatory Cytokine Production Current Pharmaceutical Biotechnology, 2014, Vol. 15, No. 2 181
tenuates visceral nociception and inflammation in mice. Fitoterapia,
2011, 82(2), 208-211.
 Bawankule, D.U.; Chattopadhyay, S. K.; Pal, A.; Saxena, K.;
Yadav, S.; Faridi, U.; Darokar, M.P.; Gupta A.K.; Khanuja, S.P.S.
Modulation of inflammatory mediators by coumarinolignoids from
Cleome viscose in female swiss albino mice. Inflammopharmacol-
ogy, 2008, 16, 272-277.
 Yadav, N.P.; Meher, J.G.; Pandey, N.; Luqman, S.; Yadav, K.S.;
Chanda, D. Enrichment, development, and assessment of indian
basil oil based antiseptic cream formulation utilizing hydrophilic-
lipophilic balance approach. BioMed. Res . Int., 2013, 410686, 9.
 Morris, G.M.; Goodsell, D.S.; Halliday, R.S.; Huey, R.; Hart, W.
E.; Belew, R. K.; Olson, A.J. Automated Docking Using a La-
marckian Genetic Algorithm and Empirical Binding Free Energy
Function. J. Comput. Chem., 1998, 19, 1639-1662.
 Perez, A.; Jansen-Chaparro, S.; Saigi, I.; Bernal-Lopez, M.R.;
Minambres, I.; Gomez-Huelgas, R. Glucocorticoid-induced hyper-
glycemia. J. Diabetes, 2014, 6, 9-20.
 Torrado, S.; Torrado, S.; Agis, A.; Jimenez, M.E.; Cadórniga, R.
Effect of dissolution profile and (−)-α-bisabolol on the gastrotoxic-
ity of acetylsalicylic acid. Pharmazie, 1995, 50, 141-143.
 Shishodia, S.; Aggarwal, B.B. Diosgenin inhibits osteoclastogene-
sis, invasion, and proliferation through the downregulation of Akt, I
kappa B kinase activation and NF-kappa B-regulated gene expres-
sion. Oncogene, 2006, 25, 1463-1473.
 Boller, S.; Soldi, C.; Marques, M.C.; Santos, E.P.; Cabrini, D.A.;
Pizzolatti, M.G.; Zampronio, A.R.; Otuki, M.F. Anti-inflammato ry
effect of crude extract and isolated compounds from Baccharis il-
linita DC in acute skin inflammation. J. Ethnopharmacology, 2010,
 Murakawa, M.; Yamaoka, K.; Tanaka, Y.; Fukuda, Y. Involvement
of tumor necrosis factor (TNF)-alpha in phorbol ester 12-O-
tetradecanoylphorbol-13-acetate (TPA)-induced skin edema in
mice. Biochem. Pharmacol., 2006, 9, 1331-1336.
 Kim, E.J.; Park, H.; Kim, J.; Park, J.H. 3,3'-diindolylmethane sup-
presses 12-Otetradecanoylphorbol- 13-acetate-induced inflamma-
tion and tumor promotion in mouse skin via the downregulation of
inflammatory mediators. Molecul. Carcinogen., 2010, 49, 672-683.
 Zima, T.; Fialova, L.; Mestek, O.; Janebova, M.; Crkovska, J.;
Malbohan, I.; Stipek, S.; Mikulikova, L.; Popov, P. Oxidative
stress, metabolism of ethanol and alcohol related diseases. J. Bio-
medic. Sci., 2001, 8, 59-70.
 Scott, J.A.; King, G.L. Oxidative stress and antioxidant treatment
in diabetes. Ann. NY Acad. Sci., 2004, 1031, 204-13.
 Murphy, M., Carmichael, A.J. Transdermal drug delivery systems
and skin sensitivity reactions. Incidence and management. Amer. J.
Clin. Dermatol., 2000, 1, 361-618.
 Yadav, D.K.; Mudgal, V.; Agrawal, J.; Maurya, A.K.; Bawankule,
D.U.; Chanotiya, C.S.; Khan, F.; Thul, S.T. Molecular d ocking and
ADME studies of natural compounds of Agarwood oil for topical
anti-inflammatory activity. Curr. Comput. Aided Drug Design,
2013, 9, 360-370.
Received: April 14, 20 14 Revised: May 23, 2014 Accepted: May 26, 2014