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Biological Effects and Modes of Action of Carvacrol in Animal and Poultry Production and Health - A Review

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| The carvacrol compound is an antioxidant nutrient, used to enhance growth and productive performance via modification and activation of gastrointestinal tract structure and function and to inhibit/prevent cancer initiations. Numerous studies performed on animal diets supplemented with phytogenic supplements/feed additives containing natural antioxidants such as carvacrol demonstrated its capability to improve performance indices, feed utilization, immune functions and health of livestock as well as reducing the risks of different animal diseases like cancer and other diseases. Such properties could be due to its ability as antimicrobial, antioxidant, antifungal, immunomodulatory, anticancer and anti-inflammatory agents by preventing free radicals and hazardous compounds from interacting with cellular DNA and its ability to change the gut microflora, improving digestion coefficient and absorption of nutrient compounds. The present review illustrates the chemical and physical proprieties, modes of action, metabolism and excretion, biological properties, natural sources and beneficial aspects of carvacrol in animal and poultry production and health.
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INTRODUCTION
Carvacrol is a monoterpenoid phenol predom-
inantly found in oregano (Origanum vulgare),
thyme (ymus vulgaris), pepperwort (Lepidium a-
vum) and wild bergamot, also produced naturally by
isolation of essential oil from some plants (Kintzios,
2002; Sokmen et al., 2004; Barnes et al., 2007; Tang
et al., 2011; Jamali et al., 2012; Kim et al., 2013). e
carvacrol amount in marjoram and hop marjoram
(Dittany of Crete) are 50 and 70%, respectively. While,
the oil extracted from thyme plant contains carvacrol
percentage between 5 -75 (León-Rodríguez, 2008).
Several in vitro and in vivo studies described dierent
bioactivity of carvacrol nutrient, including antibac-
terial, antioxidant, antiseptic, antispasmodic, growth
promoter, antifungal, antiviral, anti-inammatory,
expectorant, antitussive, immunomodulatory and
Review Article
Abstract | e carvacrol compound is an antioxidant nutrient, used to enhance growth and pro-
ductive performance via modication and activation of gastrointestinal tract structure and function
and to inhibit/prevent cancer initiations. Numerous studies performed on animal diets supplement-
ed with phytogenic supplements/feed additives containing natural antioxidants such as carvacrol
demonstrated its capability to improve performance indices, feed utilization, immune functions and
health of livestock as well as reducing the risks of dierent animal diseases like cancer and other
diseases. Such properties could be due to its ability as antimicrobial, antioxidant, antifungal, immu-
nomodulatory, anticancer and anti-inammatory agents by preventing free radicals and hazardous
compounds from interacting with cellular DNA and its ability to change the gut microora, improv-
ing digestion coecient and absorption of nutrient compounds. e present review illustrates the
chemical and physical proprieties, modes of action, metabolism and excretion, biological properties,
natural sources and benecial aspects of carvacrol in animal and poultry production and health.
Keywords | Carvacrol, Nutrition, Antioxidant, Antimicrobial, Anticancer, Immunity, Health, Pro-
duction performance, Animal, Poultry, Human
MahMoud alagawany1*, MohaMed ezzat abd el-hack1, Mayada Ragab FaRag2, Ruchi
tiwaRi3, kuldeep dhaMa4
Biological Eects and Modes of Action of Carvacrol in Animal
and Poultry Production and Health - A Review
Editor | Ruchi Tiwari, College of Veterinary Sciences, Department of Veterinary Microbiology and Immunology Uttar Pradesh Pandit Deen Dayal Upadhayay
Pashu Chikitsa, Vigyan Vishvidhyalaya Evum Go-Anusandhan Sansthan (DUVASU), Mathura (U.P.) – 281001, India.
Special Issue | 2 (2015) “Reviews on Trends and Advances in Safeguarding Terrestrial /Aquatic Animal Health and Production”
Received | February 17, 2015; Revised | March 18, 2015; Accepted | March 19, 2015; Published | March 23, 2015
*Correspondence | Mahmoud Alagawany, Zagazig University, Zagazig, Egypt; Email: dr.mahmoud.alagwany@gmail.com
Citation | Alagawany M, El-Hack MEA, Farag MR, Tiwari R, Dhama K (2015). Biological eects and modes of action of carvacrol in animal and poultry pro-
duction and health - a review. Adv. Anim. Vet. Sci. 3(2s): 73-84.
DOI | http://dx.doi.org/10.14737/journal.aavs/2015/3.2s.73.84
ISSN (Online) | 2307-8316; ISSN (Print) | 2309-3331
Copyright © 2015 Alagawany 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.
1Poultry Department, Faculty of Agriculture; 2Forensic Medicine and Toxicology Department, Veterinary Medicine
Faculty, Zagazig University, Zagazig 44111, Egypt; 3Department of Veterinary Microbiology, College of Veterinary
Sciences, Uttar Pradesh Pandit Deen Dayal Upadhayay Pashu Chikitsa Vigyan VishwaVidyalaya Evam Go-Anu-
sandhan Sansthan (DUVASU), Mathura (Uttar Pradesh) – 281001, India; 4Division of Pathology, Indian Veteri-
nary Research Institute, Izatnagar, Bareilly, 243122,Uttar Pradesh, India.
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chemopreventive as well as modier of rumen micro-
bial fermentation and reduction of methane emission
(Luna et al., 2010; Soltanab et al., 2011; Hashemipo-
ur et al., 2013; Bravo et al., 2014).
Carvacrol is molecule that has crucial bioactivities on
poultry and animal physiology and metabolism (Rein-
er et al., 2009), this compound could have antioxidant
action on poultry meat when added in the diet. Car-
vacrol plays a critical role as natural antioxidant in the
reduction of lipid peroxidation which leading to oxi-
dative destruction of cellular membranes (Rhee et al.,
1996; Yanishlieva et al., 1999). Moreover, the delete-
rious eect of these compounds may lead to increase
in the production of toxic metabolites (free radicals)
and also to apoptosis. On the other hand, Bavadekar
(2012) reported that carvacrol promotes cell death in
prostate cancer cells.
Several studies have been reported the addition of
some phytogenic additives or their products such as
cold pressed oil, essential oil or extracts to animal
and poultry diets that improved live body weight,
body weight gain, feed conversion ratio, immune re-
sponse, antioxidant status, carcass traits and quality,
and lowered morbidity and mortality rates (Ashour et
al., 2014; Farag et al., 2014; Alagawany et al., 2015a,
2015b; Dhama et al., 2015). e current review covers
many important aspects including the mechanisms of
action, metabolism and excretion, biological activities
and benecial applications of carvacrol in animal and
poultry production and health.
caRVacRol SouRceS
Carvacrol is a component of some medicinal plants,
such as black cumin (Nigella sativa), oregano (Ori-
ganum compactum), Monarda didyma, Origanum
dictamnus, Origanum microphyllum, Origanum onites,
Origanum scabrum, Origanum vulgare, thyme (ymus
glandulosus), savory (Satureja hortensis) (Aligiannis et
al., 2001; De Vincenzi et al., 2004; Coskun et al., 2008;
Liolios et al., 2009; Figiel et al., 2010). Also, carvacrol
has been produced by chemical and biotechnological
synthesis via metabolic engineered microorganisms
(More et al., 2007).
CHEMICAL AND PHYSICAL
CHARACTERISTICS
Carvacrol is an isomer and derivative of phenol,
the chemical formula of carvacrol (cymophenol) is
C6H3CH3 (OH) (C3H7), a monoterpenoid phe-
nol (Bouchra et al., 2003; De Vincenzi et al., 2004).
Carvacrol is also named 5-isopropyl-2-methylphenol
or 2-Methyl-5-(1-methylethyl)-phenol according to
International Union of Pure and Applied Chemis-
try (IUPAC). e structural formula of carvacrol is
shown in Figure 1.
Figure 1: Basic structural formula of carvacrol and its
derivative
Carvacrol is a liquid and has the same taste of thy-
mol. e density of carvacrol ranges from 0.976g/
cm3 at 20°C to 0.975g/cm3 at 25°C. Carvacrol boils
at 237~238°C, while its melting point is 1. It can be
volatile with steam. Carvacrol is highly lipophilic; the
solubility of carvacrol is very high in carbon tetrachlo-
ride, ethanol, diethyl ether, acetone; but insoluble in
water (Ultee et al., 2000). Yadav and Kamble (2009)
reported that formation of carvacrol could be resulted
from alkylation of o-cresol with propylene or isopro-
pyl alcohol (IPA) over solid acid catalysts.
MODES OF ACTION AND
BIOLOGICAL ACTIVITIES
Several modes of action could be obtained by using
phytogenic additives, such as aecting feed consump-
tion, enhancing digestive enzymes secretion and in-
creasing the motility of the digestive tract; antimi-
crobial activity, antiviral activity, antioxidative activity,
endocrine and immune stimulation; anthelminthic,
coccidiostat and anti-inammatory activity (Akyu-
rek and Yel, 2011). Basmacioğlu et al. (2010) armed
that antioxidative and antimicrobial ecacy of the ac-
tive component of plant extracts or essential oils had
been used in a lot of in vitro or in vivo experiments,
but some questions still remain unanswered concern-
ing the mode of action, optimal dosage, and pathway
of metabolism of these additives in poultry.
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Figure 2: Modes of action and biological activities of carvacrol
In fact, carvacrol component is added to various in-
gredients, such as nonalcoholic beverages (28.54 mg/
kg), baked goods (15.75 mg/kg), chewing gum (8.42
mg/kg), etc. (Fenaroli, 1995). However, the mode of
action of this compound was unknown by many re-
searchers. A good knowledge of carvacrol mode of
action is very required regarding application in nutri-
tional systems. Formerly, Ultee et al. (1998) reported
the antimicrobial activity of carvacrol on pathogen
Bacillus cereus. Carvacrol is a hydrophobic compound
and has an eective impact on biological membranes.
e modes of action and benecial aspects of carvac-
rol are shown in Figure 2.
METABOLISM AND EXCRETION
e metabolism and excretion of carvacrol in the
body is very quick. e major metabolic pathway of
carvacrol is related to the esterication of phenolic
group with glucuronic acid (C6H10O7) and sulfuric
acid (H2SO4). But, a minor route of carvacrol metab-
olism is transformation of the end methyl groups to
primary alcohols. In an experiment on male albino
rats, Austgulen et al. (1987) found that rats excreted
a major percent of administered carvacrol (1 mmol/
kg) in urine, as its sulphate and glucuronide conju-
gates, with extensive oxidation of the methyl groups
mainly and this gave derivatives of benzyl alcohol and
2- phenylpropanol in addition to their corresponding
carboxylic acids. A minor metabolite resulting from
ring hydroxylation has also been detected. Moreover,
the residual of carvacrol or its derivatives in urine was
very small after one day only; this phenomenon is a
strong indicator of the high speed of the carvacrol
metabolism and excretion during the rst day.
Michiels et al. (2008) carried out some experiment
with gastric fermentation simulation of pig. Results
reported 29% degradation of carvacrol in cecum, while
jejunum was not aected. When piglets received oral
feeding of 13.0, 13.2, 12.5 and 12.7 mg carvacrol /kg
body weight, they showed half-life between 1.84 and
2.05 hours in the whole digestive tract. Carvacrol was
almost absorbed completely in the proximal small in-
testine and the stomach. e concentrations of plasma
(total of free and conjugated compound) maximized
at 1.39 hours and followed by high concentrations in
the urine.
BENEFICIAL ASPECTS OF
CARVACROL
iMpRoVing nutRientS bioaVailability and
gRowth/pRoductiVe peRFoRMance
A number of animal and poultry trials have been
conducted previously to establish the dependency
and functionality of carvacrol and supplementation
of it in animal and poultry diets. Hashemipour et al.
(2013) reported that feed supplementation with thy-
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mol + carvacrol mixture by 60, 100, and 200 mg/kg of
diet improved growth performance, digestive enzyme
activities, and antioxidant enzyme activities besides
inhibiting lipid peroxidation in broiler chicks. e
concentration of IgG in serum was enhanced in the
diet supplemented with dierent plant extracts such
as thyme and oregano compared to the control diet in
mice and pigs (Namkung et al., 2004).
In 17 days old poults which ate a diet with supple-
mentation of a plant extract containing carvacrol at
300 mg/kg diet, Jamroz and Kamel (2002) observed
daily body weight gain and feed conversion ratio to
be improved by 8.1 and 7.7 %, respectively. Lee et al.
(2003a) reported that increased eciency of feed uti-
lization could be the explanation of thymol and car-
vacrol eects on performance. Hernandez et al. (2004)
stated that the improvement of broiler performance
fed diets supplemented with several additives such as
thymol and carvacrol, pepper essential oils (200 mg/
kg), and rosemary extracts (5,000 mg/kg) could be at-
tributed to its benecial eects on digestibility.
Jaafari et al. (2012) fed one day female broilers with
cholesterol-free or cholesterol-rich diets supplement-
ed with 200 ppm carvacrol for four weeks of age and
observed that feed intake and weight gain were re-
duced but feed conversion got improved. Moreover,
plasma concentration of triglyceride was lowered
with no eect on plasma content of cholesterol due to
dietary carvacrol addition. When carvacrol was sup-
plemented with corn-soybean meal basal diet sup-
plemented with carboxymethyl cellulose, there were
no any signicant eects on feed eciency or plasma
content of cholesterol. Lee et al. (2003b) reported a
negative eect on broilers body weight when feeding
on 200 ppm carvacrol /kg diet with the same dose of
cinnamaldehyde. A study of Lee et al. (2004) con-
rmed the non-signicant impact on productive per-
formance traits i.e. live body weight, feed consump-
tion, feed eciency and ileal content of microbiota by
feeding broiler chickens on carvacrol with thymol and
organic acids. ese previous studies showed an inde-
cisive inuence of carvacrol on the eciency of feed
in broiler chickens and additional studies are want-
ed to get assured results as suggested by Umaya and
Manpal (2013). Supplementing the diet of one day
old broilers with 5.0 ppm carvacrol for seven days of
age, caused an improvement in body weight gain and
depressed oocyte shedding, gut lesions in addition
to lowering gene expression of proinammatory cy-
tokine during coccidiosis when challenging birds by
Eimeria acervulina (Lillehoj et al., 2011). Moreover,
lipid metabolism, estrogen and androgen metabolism
in intestinal intraepithelial lymphocytes were reg-
ulated due to carvacrol supplementation in broilers.
Feeding chickens on diet supplemented with 5.0 ppm
carvacrol/ kg altered the expression of 74 genes in in-
testinal intra epithelial lymphocytes. Treatment with
carvacrol also led to an upregualtion of many genes
associated with the metabolic and endocrine system
such as protease serine 3 (PRSS3) and selenoprotein
X, 1 (SEPX1) (Lillehoj et al., 2011). Based on the
aforementioned results, several studies should be tak-
en place to help in understanding the carvacrol mo-
lecular mechanism in the digestive tract of chicken
and simplify the development of novel dietary ways to
immunomodulate host response in disease or normal
cases.
e consumer attention has been raised within the
past decades regarding the quality of meat and its
products. e poultry meat content of polyunsaturat-
ed fatty acids is high; so it is susceptible to oxida-
tive deterioration, which negatively impacts the meat
quality. Broilers fed diet contained 150 ppm of car-
vacrol through the experimental period (1 day - 42
days of age) caused a reduction in thiobarbituric acid
production which is a proof of lipid peroxidation in
samples of thigh (stored for 5-10 days). Similar re-
sults obtained by Yanishlieva et al. (1999); Annalisa
et al. (2009); Mastromatteo et al. (2009); Kim et al.
(2010) and Akalin and Incesu (2011) revealed that
carvacrol supplementation minimized lipid oxidation
and microbial load in chicken patties stored at low
temperature (0-3°C), as well as improving shelf life
and quality of poultry meat. So, using carvacrol as a
natural antioxidant could improve quality of poultry
products.
antiViRal actiVity
Herbal plants and their derivatives or extracts have
been evaluated for their possible antiviral prosperities,
including the cold pressed or essential oils of certain
commonly used culinary herbs ( Jassim and Naji,
2003; Sokovic et al., 2010). Carvacrol plays a key role
as antiviral component against human rotavirus (RV).
On the same context, Mexican oregano (Lippia gra-
veolens) extract and oil as well as carvacrol compo-
nent are able to reduce/inhibit the viral diseases in
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animal and human. Specically, the antiviral activity
of oregano and its phenolic components on acyclovir
resistant herpes simplex virus type 1 (ACVRHHV-1)
and human respiratory syncytial virus (HRSV) and of
carvacrol on RV have been documented (Bernstein,
2009; Pilau et al., 2011).
Oregano essential oils including carvacrol compound
have been strongly promoted as natural antiviral fac-
tors eective against many viral diseases such as the
pandemic H1N1 virus (Vimalanathan and Hudson,
2012). On the contrary, Sokmen et al. (2004) not-
ed that anti-inuenza virus activity was not aected
by supplementation of oils or extracts derived from
oregano. Gilling et al. (2014) reported that carvacrol
as a natural food is very eective in inhibiting human
norovirus within one hour of exposure by acting di-
rectly on the viral capsid.
antiMicRobial actiVity
e antimicrobial eects of essential oils have been
due to the presence of phenolic compounds, such as
carvacrol, thymol, eugenol, curcumin and cinnamal-
dehyde which are presented in essential oils of orega-
no, thyme, clove, turmeric and cinnamon, respectively
(Tsao and Zhou 2000; Lambert et al. 2001; Veldhu-
izen et al., 2006; Alagawany et al., 2015b). Sikkema
et al. (1995), Adam et al. (1998), Weber and de Bont
(1996), Ben-Arfa et al. (2006) and Nostro and Pa-
palia (2012) mentioned that the benecial/inhibitory
eects of phenolic compounds could be attributed to
the interactions between the eective compounds and
cell membrane of microorganisms and is usually asso-
ciated with the hydrophobicity of these compounds.
Arsi et al. (2014) showed that campylobacter numbers
were reduced with 1% carvacrol supplementation, or
a combination of both thymol and carvacrol at 0.5%.
Friedman et al. (2002), Sokovic et al. (2002), Nastro
et al. (2004), and Baser (2008) found antimicrobial
inuences of carvacrol against many species of mi-
crobes such as Pseudomonas, Aspergillus, Salmonella,
Streptococci, Listeria, Bacillus and Fusarium. Burt et al.
(2005 and 2007) observed that carvacrol supplement
as antimicrobial component has a signicant impact
on harmful bacteria including Escherichia coli and Sal-
monella numbers in chickens, this eect may be attrib-
uted to inhibit the growth of pathogenic bacteria by
carvacrol vapour. Johny et al. (2010) postulated that
carvacrol and eugenol decreased (P≤ 0.05) Salmonella
Enteritidis and C. jejuni counts in chicken cecal con-
tents to <1.0 log10 cfu/ml at 50 and 75 mM and 20
and 30 mM, respectively.
antioxidant actiVity and
ScaVenging oF FRee RadicalS
Free radicals or reactive oxygen intermediates are gen-
erated by cells during the normal metabolism. When
free radicals such as superoxide radical (O2.-), hy-
drogen peroxide (H2O2) and hydroxyl radical (OH.)
are accumulated excessively, this leads to a damage in
tissue and privation of many cellular functions. Car-
vacrol as an antioxidant protects the cells against free
radicals. Moreover, antioxidants inhibit prostaglandin
synthesis and induct drug-metabolizing enzymes in
addition to many biological activities as reported by
Azirak and Rencuzogullari (2008).
Some studies assured the eciency of carvacrol in
scavenging free radicals i.e. nitric oxide, superoxide
radicals, peroxyl radicals and hydrogen peroxide (Ko-
hen and Nyska, 2002; Aristatile et al., 2010). e ex-
istence of hydroxyl group (OH) which linked to aro-
matic ring is suggested to be the reason for the highly
antioxidant activity of carvacrol either in vitro or in
vivo as explained by Aeschbach et al. (1994) and Gui-
maraes et al. (2010). e reaction of carvacrol with a
free radical is facilitated due to its weak acid character,
so donating hydrogen atoms to an unpaired electron,
producing another radical that is stabilized by electron
scattering generated at a molecule resonance structure
(Aristatile et al., 2010).
Supplemental oregano by 50 to 100 mg/kg to broiler
chick diets exerted an antioxidant eect in the broiler
tissues (Botsoglou et al., 2002). Ruberto et al. (2000),
Alma et al. (2003), and Luna et al. (2010) reported
that the diet unsupplemented with carvacrol or thy-
mol has similar eectiveness to inhibit the oxidation
of lipids than the synthetic antioxidant supplementa-
tion such as butylated hydroxytoluene, ascorbic acid
and vitamin E, and could be considered good natural
additives to be applied in animal and poultry industry
to improve the performance and health. Animals fed
diet supplemented with carvacrol had greater concen-
trations of SOD and GSH-PX and more level of poly
unsaturated fatty acids (PUFA) in the brain phospho-
lipids than the unsupplemented control (Youdim and
Deans, 2000).
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iMMunoModulatoRy eFFect
Improving poultry immunity is one of the main goals
to prevent infectious diseases. Immunodeciency
could occurr by several factors including abuse of anti-
biotics, vaccination failure or immune-suppressive in-
fectious diseases. To improve the bird’s immunity and
decrease the susceptibility to infectious diseases, im-
mune stimulators could be used. Acamovic and Brooker
(2005) and Silveira et al. (2013) reported that herbs
rich in avonoids such as thyme and carvacrol could
improve the immune functions through acting as an-
tioxidants and extending the activity of vitamin C.
Botsoglou et al. (2002) expected to nd an improve-
ment in the immune responses of chicks because of
the assured antioxidant, antibacterial and antiviral
activities of carvacrol which had been reported by
many researchers. Lillehoj et al. (2011) pointed out
that feeding birds with diets containing plant-derived
phytonutrients such as carvacrol, thymol, cinnamalde-
hyde, capsicum and oleoresin signicantly improved
the immune response in chickens and lowered poul-
try infectious diseases. Furthermore, Hashemipour
et al. (2013) reported that feeding birds with diets
contained carvacrol plus thymol linearly increased
(P<0.01) the primary and secondary response against
SRBC antigen and IgG.
anti-caRcinogenic and
antiplatelet eFFectS
Some natural antioxidants such as carvacrol exert an-
ticarcinogenic and platelet antiaggregating impacts
(Karkabounas et al., 1997 and 2002; Evangelou et
al., 1998; Liasko et al., 1998; Ipeka et al., 2005). Also,
Karkabounas et al. (2006) and Michiels et al. (2008)
armed the eect of carvacrol as anticancer and an-
tiplatelet in vivo and in vitro during hepatocellular
carcinoma, pulmonary tumors and chemical induced
carcinogenesis. As well, Aydin et al. (2007) and Jay-
akumar et al. (2012) suggested that carvacrol exhib-
its antigenotoxic activity at nontoxic concentrations
(<0.05 mM) but it needs more investigation.
Arunasree (2010), Yin et al. (2012), and Al-Fatlawi et
al. (2014) pointed out genomic DNA fragmentations
and caspase-3, -6 or -9 enzymes gene expression were
induced by carvacrol supplementation; also carvacrol
addition induced apoptosis regulatory genes in hu-
man breast cancer cell line (MCF-7) cells and retard-
ed growth. Carvacrol plays an important therapeutic
role in treating cancer including cervical cancer cells
(Arunasree, 2010; Mehdi et al., 2011).
hepatopRotectiVe eFFect
In a D-galactosamine induced rat model, carvacrol
exhibited a hepatoprotective role either in vivo or ex
vivo. Aeschbach et al. (1994), Aristatile et al. (2009a)
and Guimaraes et al. (2010) revealed that using car-
vacrol at the level of 80 mg/kg body weight in rat
helped restoring the concentrations of lipid peroxida-
tion products, lipids content in kidney, liver and blood
plasma to its normal values. In addition, enzymic and
non-enzymic antioxidants concentrations induced by
D- galactosamine also restored to normal by carvacrol.
e aforementioned authors added that the treatment
with carvacrol restored and controlled the damage of
DNA and the reductions in mitochondrial enzymes
which induced by D-galactosamine.
In fact, lake of glucose and oxygen needed for me-
tabolism of the cell could be happened if blood ow
to an organ was insucient or stopped resulting in
ischemia. Reperfusion is a term of the restoration of
blood ow to the tissue after the elimination of the
causative agent for ischemia. As a result to reperfu-
sion, toxic products pass to the circulation system.
During liver surgery, renal I/R injury and liver trans-
plantations, hepatic ischemia is a frequent problem.
Canbek et al. (2008), Aristatile et al. (2009b) reported
that carvacrol protects liver during renal I/R injury
and hepatic I/R injury through improving liver anti-
oxidant defence and minimizing the products of lipid
peroxidation.
anti-inFlaMMatoRy and anti-
hypeRnociceptiVe eFFectS
Hypersensitivity of nociceptive pathways causes in-
ammatory hyperalgesia or it could be called hy-
pernociception. e immune system cells release the
mediators such as interleukins, cytokines or tumor
necrosis factor-α during inammation. e previous
action activates the higher order neurons which ex-
ist in the transmission of the nociceptive input and
also activates the primary nociceptors. Trabace et al.
(2011) stated that pain sensitivity increased in labo-
ratory animals as a result to the aforementioned hy-
persensitivity of nociceptive pathways which contrib-
utes to hypernociception. e threshold sensitivity of
mice exposed to carrageenan was improved by using
carvacrol at the dose of 50 and 100 mg/kg compar-
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ing to indomethacin and standard drug. Marchand el
al. (2005) reported that the method of carvacrol in
inhibiting hypernociception is to inhibit the migra-
tion of mononuclear cells and neutrophils concluded
in the production of proinammatory cytokines such
as nitric oxide and consequently a decrease in prosta-
glandins. e morphology of the cells did not aect
due to carvacrol treatment excepting a decrease in the
TNF-α levels in pleural lavage. Hotta et al. (2010),
and Guimaraes et al. (2012) found an anti-hyperno-
ciceptive eect of carvacrol by decreasing the levels of
enzyme responsible for inducing nitric oxide synthase
and in turns the macrophages content of nitric oxide.
Marchand et al. (2005), Kaufmann et al. (2011), and
Uyanoglu et al. (2011) had contradicting reports re-
garding including the antioxidant eect of carvacrol
in controlling nitric oxide production and lipid perox-
idation during hypernociception.
anti-obeSity eFFect
Obesity is a medical condition in which excess body
fat accumulates to the extent that it may have a nega-
tive eect on health, leading to increased health prob-
lems. It is like other chronic diseases such as hyper-
lipidemia, cancers and diabetes. Umaya and Manpal
(2013) stated that the main factor in enhancing obesi-
ty and attributed to the metabolic diseases in humans
and animal models is the consumption of high levels
of fat in the diet and they found that carvacrol caused
an inhabiting of fat accumulation between cells and
adipocyte dierentiation in mouse embryo 3T3- L1
cells. Also, results showed that diet high in fat and
supplemented with carvacrol decreased total visceral
fat, plasma and liver total cholesterol, HDL-choles-
terol, triglyceride and free fatty acids of mice. Moreo-
ver, carvacrol decreased the expression of adipogene-
sis related genes- broblast growth factor receptor in
visceral adipose tissues. Also, carvacrol decreased the
expression of receptors which stimulates the intake of
fat rich diet such as galanin receptor 1 and 2.
Wieten et al. (2010), and Cho et al. (2012) found that
free fatty acid levels and the mRNA and protein levels
of toll-like receptors were reduced by carvacrol. Free
fatty acids in high levels are reported in obese ani-
mals, because of their release either from high fat diet
or from adipose tissues. Carvacrol as anti-obese drug
needs for more detailed studies to be recommended
for this purpose.
CONCLUSION
is review highlights the benecial applications of
the dietary addition of carvacrol as a natural antioxi-
dant or growth enhancer with useful activities on feed
eciency, nutrient bioavailability, immunity, oxidative
status, egg quality parameters and growth/productive
performances. Furthermore, useful impacts of lowered
serum and meat MDA, lipid peroxidation have been
noted in poultry and animal fed rations supplement-
ed with carvacrol, indicating the benecial eects and
important role of carvacrol dietary supplementation
which could be due to its pharmacological eects and
benecial health eects, such as antimicrobial, anti-
oxidant, anticancer, antiplatelet, antiviral, anti-inam-
matory, antifungal, and growth promoting properties.
Exploration of the carvacrol modes of action like nu-
tritional, pharmacological, health benets and biolog-
ical properties may play crucial role in its benecial
usages in poultry farm and animal management sys-
tems by providing further understanding of the health
applications and increasing performance parameters
in agriculture species.
ACKNOWLEDGEMENTS
All the authors of the manuscript thank and acknowl-
edge their respective Universities and Institutes.
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... Scavenging of free radicals, inhibit prostaglandin synthesis and induct drug-metabolising enzymes. The reaction of carvacrol with a free radical is facilitated due to its weak acid character, so donating hydrogen atoms to an unpaired electron, producing another radical that is stabilised by electron scattering generated at a molecule resonance structure Alagawany et al. (2015) Immunomodulatory Acting as antioxidants and extending the activity of vitamin C. Improvement in the immune responses of chicks because of the assured antioxidant, antibacterial and antiviral activities of carvacrol. Alagawany et al. (2015) Anti-carcinogenic Genomic DNA fragmentations and caspase-3, -6 or -9 enzymes gene expression were induced by carvacrol; also carvacrol induces apoptosis regulatory genes in human cancer and retarded growth Zeytun and Ozkorkmaz (2021) Anti-inflammatory and anti-hypernociceptive Inhibit the migration of mononuclear cells and neutrophils concluded in the production of pro-inflammatory cytokines such as nitric oxide and consequently a decrease in prostaglandins. ...
... The reaction of carvacrol with a free radical is facilitated due to its weak acid character, so donating hydrogen atoms to an unpaired electron, producing another radical that is stabilised by electron scattering generated at a molecule resonance structure Alagawany et al. (2015) Immunomodulatory Acting as antioxidants and extending the activity of vitamin C. Improvement in the immune responses of chicks because of the assured antioxidant, antibacterial and antiviral activities of carvacrol. Alagawany et al. (2015) Anti-carcinogenic Genomic DNA fragmentations and caspase-3, -6 or -9 enzymes gene expression were induced by carvacrol; also carvacrol induces apoptosis regulatory genes in human cancer and retarded growth Zeytun and Ozkorkmaz (2021) Anti-inflammatory and anti-hypernociceptive Inhibit the migration of mononuclear cells and neutrophils concluded in the production of pro-inflammatory cytokines such as nitric oxide and consequently a decrease in prostaglandins. Carvacrol decreases the levels of enzyme responsible for inducing nitric oxide synthase and in turns the macrophages content of nitric oxide. ...
... Guimarães et al. (2010) Anti-obesity Carvacrol decreased the expression of adipogenesis related genes fibroblast growth factor receptor in visceral adipose tissues. Also, carvacrol decreased the expression of receptors which stimulates the intake of fat-rich diet such as galanin receptors 1 and 2. Alagawany et al. (2015) carvacrol has been produced by chemical and biotechnological synthesis via metabolic-engineered microorganisms (More et al., 2007). ...
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Background Thymol and carvacrol as natural essential oils and phenol compounds are components derived from some medicinal plants, such as thyme and oregano species. Objectives The increasing demands in organic and healthy meat and egg consumption in human society have made it necessary to consider alternative natural compounds for the replacement of chemical compounds in poultry production. The chemical compounds can remain in meat and eggs and cause complications in human health. Therefore, these natural compounds can be fed with a higher safety in poultry production with specific effects. In this regard, the role of thymol and carvacrol as natural compounds in the poultry production has been discussed in the review. Methods In this study, by searching for keywords related to thymol and carvacrol in poultry production in Google Scholar database, the articles related to different aspects of the biological effects of these two phytogenes in poultry production were selected and analyzed. Results A review of previous studies has shown that thymol and carvacrol possess a wide range of biological activities, including antibacterial, antiviral, antioxidant, anti-inflammatory, modulating of immunity response and regulating of the gut microbial population. Also, in meat type chickens can promote growth and influence feed utilization. The beneficial effect of this compound was evaluated in hepatic toxicity and demonstrated as a hepatoprotective compound in chickens. Furthermore, these compounds can affect the behavior of layers and influence egg composition, eggshell thickness, and the sensory quality of eggs. Conclusion It seems that with the increasing demand for healthy protein products, these compounds can be used to improve performance as a substitute alternative for chemical compounds in healthy poultry farms.
... Ionophores/polyether antibiotics are lipid-soluble compounds (with multiple cyclic ether groups) mainly produced as a by-product from the fermentation process of Streptomyces spp. Table 7. Thymus vulgare Alagawany et al. (2015) Lepidium flavum Alagawany et al. (2015) Thymol ...
... Ionophores/polyether antibiotics are lipid-soluble compounds (with multiple cyclic ether groups) mainly produced as a by-product from the fermentation process of Streptomyces spp. Table 7. Thymus vulgare Alagawany et al. (2015) Lepidium flavum Alagawany et al. (2015) Thymol ...
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Coccidiosis is a major parasitic disease in the poultry industry, with great economic implications worldwide. It is a ubiquitous protozoan infection caused by several species of the genus Eimeria (host-specific) that colonize and reproduce in the intestine of birds, ultimately altering the health and performance of the flock. At present, several methods are used to diagnose coccidiosis in poultry, including field and laboratory techniques (intestinal lesion scoring, oocyst counting in feces, and biochemical and molecular diagnosis). Traditionally, diagnosed flocks have been treated either by vaccination to improve the active immunity of the birds against coccidiosis or supplementation of prophylactic anticoccidials to ameliorate the deleterious effects of coccidiosis. However, these methods has certain drawbacks such as vaccine-induced coccidiosis, drug resistance, and residual drug accumulation in the host. Consequently, alternative safe anti-coccidial agents, including the use of phytogenic compounds, have been explored for preventing coccidiosis. Here, we provide a simple overview of the literature on poultry coccidiosis by focusing on the etiology, diagnostic practices, and preventive measures.
... Essential oils are aromatic oily liquids obtained by distillation from different plant parts [17]. Carvacrol (2-methyl-5-(1-methylethyl)-phenol) is a phenolic monoterpene mainly found in essential oils extracted from thyme (Thymus vulgaris), oregano (Origanum vulgare) and essential oil of some plants [18]. Carvacrol nutrient has pivotal bioactivities including antiviral, antioxidant, anti-inflammatory and immunomodulatory activities [18,19]. ...
... Carvacrol (2-methyl-5-(1-methylethyl)-phenol) is a phenolic monoterpene mainly found in essential oils extracted from thyme (Thymus vulgaris), oregano (Origanum vulgare) and essential oil of some plants [18]. Carvacrol nutrient has pivotal bioactivities including antiviral, antioxidant, anti-inflammatory and immunomodulatory activities [18,19]. Anti-IBV activity of fifteen plant extracts including Origanum vulgare and Thymus vulgaris was investigated in vitro using Vero cells and the results showed that the extract of Origanum vulgare and Thymus vulgaris had antiviral activity before and during infection [20]. ...
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Infectious bronchitis virus (IBV) is one of the major respiratory diseases of broiler causing huge economic losses. The inability to control IBV using different vaccination programs owing to the high mutation rate and recombination ability of the RNA genome generates IBV variants. This study was designed to give a specific perspective of carvacrol effect on early immune response, viral shedding titer, oxidative stress, serum biochemical parameters and clinical consequences in broilers experimentally infected by IBV. One hundred and twenty-one-day old commercial broiler chicks were equally divided into 4 groups. First group was considered as control. Second group was given carvacrol, third group was infected with IBV and fourth group was given carvacrol and infected with IBV. Infection with variant IBV induced significant upregulation of chicken interferon-inducible transmembrane protein 3 (chIFITM3) gene in trachea, elevations in serum levels of Alpha-1 acid glycoprotein (α1-AGP) and Interleukin 6 (IL-6), total leucocytic count (TLC), heterophil/lymphocyte (H/L) ratio and oxidative stress in lung and kidney tissues. Beside, histopathological changes in trachea, lung and kidney induced by IBV, elevation of kidney function tests was detected. The pretreatment with carvacrol significantly reduced viral shedding titer, chIFITM3 gene expression, IL-6 and α1-AGP levels, leucocytic response and H/L ratio with minimization of clinical signs intensity. Also, carvacrol relieved oxidative stress, ameliorated the increased uric acid level and histopathological alterations in kidney and lung caused by viral infection.
... Thymol is a main constituent of commonly used EOs, such as oregano and thyme oils (Bassol e and Juliani, 2012). Carvacrol is a constituent of several medicinal plants, such as thyme, black cumin, and oregano (Alagawany et al., 2015). Carvacrol and thymol can inhibit the growth of both gram-positive and gram-negative bacteria. ...
... In our previous study, we also found that HDV increased the T-AOC and decreased MDA content in small intestine of layers under high stocking density (Wang et al., 2021). On the other hand, it has demonstrated that natural plant supplements, such as resveratrol, hesperidin, genistein, thymol and carvacrol and herbs, can be used to enhance antioxidant defense mechanisms and reduce the intensity of oxidation processes to improve quality of poultry products (eggs and meat) (Alagawany et al., 2015;Ogenik et al., 2016). Similarly, Luna et al., (2010) and Hashemipour et al. (2013) have reported that feed supplementation with 150 to 200 mg/kg thymol and carvacrol enhanced SOD and GST activities and decreased MDA concentration in thigh and breast muscle of broilers. ...
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This study was conducted to determine the effect of 25-hydroxyvitamin D (HDV) and essential oils (EO) on the uterus antioxidant capacity, egg quality and eggshell ultrastructure in laying hens. A total of 400 48-wk-old Lohmann laying hens were randomly allocated into 2 groups and fed a basal diet (control) or a basal diet supplemented with a combination of 69 μg/kg HDV and EO (including 200 mg/kg thymol and 50 mg/kg carvacrol) for 12 wk. There are 10 replicates of 20 hens each. Compared with the control, dietary HDV+EO supplementation improved (P < 0.05) egg production rate, feed efficiency, eggshell thickness and strength, and decreased (P < 0.05) the translucent egg score. Ultrastructural changes indicated that dietary HDV+EO supplementation decreased (P < 0.05) mammillary knob width, mammillary thickness and the proportion of mammillary thickness, and increased (P < 0.05) the proportion of effective thickness and total thickness of the eggshells compared with the control. Supplementation with HDV+EO complex led to higher serum HDV concentration and increased antioxidant capacity in the uterus, indicated by higher (P < 0.05) antioxidant enzyme activities [catalase (CAT), total antioxidant capacity (T-AOC) and glutathione S-transferases (GST)] and lower malondialdehyde (MDA) content. Therefore, dietary HDV and EO complex (including thymol and carvacrol) supplementation can improve the productive performance and the eggshell quality in laying hens, and the improving effect on eggshell quality may through enhancing eggshell ultrastructure and antioxidant capacity of uterus.
... Carvacrol has also been synthesized using the alkylation of Friedel-Crafts ortho-cresol with isopropyl alcohol on the substrate of solid superacid catalysts (Yadav and Kamble 2009). Carvacrol has several biological properties such as antimicrobial, antiinflammatory, antioxidant, antiseptic, and anti-cancer properties (Sharifi-Rad et al. 2018;Dai et al. 2016;Yadav and Kamble 2009;Alagawany et al. 2015). In addition, carvacrol has been reported to have good anti-cancer effects on lung cancer, breast cancer, stomach cancer, and colon cancer cell lines, but the apoptotic effects of carvacrol still need further investigation (Guimarães et al. 2015). ...
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Cancer is a complex of malignant cell growth and is one of the most challenging issues worldwide. This study aimed to design, determine, and synthesize a modified carvacrol-containing anticancer peptide sequence and its anti-cancer properties investigated against gastric cancer cell line by Real-Time RT PCR technique. Anticancer peptide sequence designed by ACAN bioinformatics software. Modified carvacrol structure designed by bioinformatics software and the anti-cancer sequence added to it. After determining the chemical and structural properties and modeling by bioinformatics software the compound was synthesized. Then, an MTT test was performed on the gastric cancer cell line. In the next step, the AGS cancer cell is exposed to the MTT concentration of the compound in a culture medium. Then, mRNA is extracted from treatment-exposed cancer cells and treatment-free cell lines, and cDNA was then synthesized from mRNA. The effect of the compound on caspase3 and bcl2 apoptosis genes is investigated by Real-Time RT PCR. Alkylation of o-cresol with isopropanol over AlCl3 as an efficient catalyst leads to the appropriate preparation of carvacrol with proper yields (75.6%). Results showed that carvacrol accompanied by Anticancer peptide at a concentration of 2.5 mg/ml had cytotoxic effects on the cervical. The inhibitory effects of carvacrol and anticancer peptide increased against inhibition of the Bax gene by 256-fold and caspase 3 by 32-fold and bcl2 decreased by eightfold. Because of the anti-apoptotic properties of modified carvacrol-containing anticancer peptide, it can be used to inhibit cancer cells as a therapeutic supplement and prevention.
... On the other hand, the current data show that the addition of BPO at 0.5 g/kg had a positive effect on the growth performance of broiler chickens. The results were corroborated by [63], reporting that black pepper enhanced the performance, feed conversion ratio, and carcass-meat safety and quality in animals. Black pepper improved nutrient digestibility by increasing digestive liquids in the stomach and decreasing pathogenic microorganisms in broiler chickens [17]. ...
Article
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Optimal combinations of essential oils (EOs) can enhance performance and maintain poultry productivity. The effects of EOs with black pepper oil (BPO) or radish seed oil (RSO) on performance and the expression of digestive enzymes, lipogenesis, immunity, and autophagy-related genes in broiler chickens were explored. Six dietary treatments for 300 one-day-old chicks were allocated as follows: controls were fed a basal diet, one group was fed an EO-supplemented diet (1.5 g/kg diet of parsley, mint, and carrot seed oils (1:1:1)), and other groups received Eos + BPO0.25, Eos + BPO0.5, Eos + RSO0.25, and Eos + RSO0.5 treatments, with a basal diet containing EOs plus BPO or RSO at the level of 0.25 or 0.5 g/kg, respectively. Supplementation with 0.5 g/kg of EOs plus BPO or RSO resulted in the most improved maximum BWG and FCR in broiler chickens. The lactobacilli population was increased in Eos + BPO0.5, followed by EOs + RSO0.5, unlike in the control. The highest expression of the CCK and PNLIP genes was identified in the Eos + BPO group. The FAS and ACC genes were upregulated, while the IgA and IL-10 genes were downregulated, with EOs plus RSO or BPO. The group that received Eos + BPO0.5, followed by Eos + RSO0.5, displayed patterns of higher expression for atg5, atg7, and atg12, with lower expression of mTOR. In summary, a new combination of EOs with 0.5 g/kg BPO had potential growth-promoting and immune-boosting effects in broiler chickens.
... Carvacrol is a structural isomer of thymol and a constituent of N. sativa that is abundant in a wide variety of herbs. It possesses antitumor, antiinflammatory, angiogenic, antiparasitic, analgesic, and antimicrobial activities (Baser, 2008), and it is also highly beneficial for animals and poultry health (Alagawany et al., 2015). Both thymol and carvacrol exert their antimicrobial activity by disintegrating the outer membrane, thereby damaging the cell membrane. ...
... The major compounds found in thyme were carvacrol and thymol; both have anti-inflammatory, antimicrobial, anti-inflammatory, and antioxidant properties (Abu-Lafi et al. 2008). Thyme EO was used to enhance growth and productive performance via modification and activation of gastrointestinal tract structures and functions, as well as inhibiting and preventing cancer (Alagawany et al. 2015). It was also found to have insecticidal and acaricidal activities (Chaieb et al. 2007). ...
Article
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The current study was conducted to evaluate the effect of eight Palestinian indigenous plant essential oils (EOs) under in vitro and in vivo conditions against Botrytis cinerea Pers.: Fr., Penicillium italicum Wehmer, and Penicillium digitatum (Pers.) Sacc., three common post- harvest pathogens of tomato and strawberry fruits. In vivo tests showed that thyme, sesame and sage EOs exhibited high antifungal activity against B. cinerea on strawberry and toma- to fruits, compared with rosemary, mint and eucalyptus. In vitro agar, disk-diffusion tests showed that B. cinerea, P. digitatum and P. italicum mycelium growth was completely inhi- bited when treated with clove and sage EOs caused 50% inhibition of B. cinerea and P. itali- cum mycelium growth. Fruit decay and fruit quality index values measured in total soluble solids and fruit flesh firmness showed that EO coated strawberries had significantly less fruit decaying and ripping compared to control, while EO coated tomatoes showed no sig- nificant difference compared to control. EO constituents fall into different chemical classes, including sterols, caffeoylquinic acids, flavonoids, terpenoids, coumarins, and acetylenes. Chemical analysis of the EO preparations using gas chromatography-mass spectrometry determined that the main components in sesame oil were octadecenoic acid-(56%) and hexadecanoic acid (26%), while clove oil consisted of eugenol (53%). In the other EOs, the principal compounds were: menthol (44% in mint oil), eucalyptol (37% in sage oil), while bornanone (18% in rosemary oil) and γ-terpinene (21% in thyme oil) were present at lower concentrations. The EO of sage plants could potentially be a useful alternative to synthetic pesticides to control post-harvest diseases and prolong the shelf life of fruit products.
Chapter
The intense poultry production with large flocks concentrated on restricted productive areas results in high bacterial loads within the poultry houses while additional administration of antibiotics to the hens negatively impacts the composition of intestinal microbiota and immunity, and, in turn, the efficiency and profitability of egg production on the farms. The composition of cecal microbiota and its sensitivity to antibiotics were studied in commercial laying hens (cross Hyline Brown) fed phytobiotics Activo and Activo Liquid at the onset of lay and at the peak of egg production and fed the diets without antibiotics. It was found that at the start (24 weeks of age) and peak (32 weeks) of egg production the phytobiotics decreased the percentages of opportunistic microbial species in the ceca in compare to control resulting in better efficiency of the digestion and better productive performance and health status in the layers. The phytobiotics also improved the sensitivity of the pathogenic and opportunistic species to different antibiotics.
Chapter
Due to the lack of prophylactic vaccines and effective treatment strategies against numerous public health conditions, viral infections remain a serious threat to global public health and socioeconomic development. The current ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, against which there is no prophylactic vaccine or licensed antiviral agents, underscores the need to continuously identify novel/effective treatment strategies against these infectious agents. Plants and plant-derived compounds have immensely contributed to the fight against numerous health conditions by providing bioactives that possess potent antimicrobial attributes, including antiviral activities. One such plant that has gathered much interest, due to its multiple medicinal properties, is the Nigella sativa plant, a flowering plant belonging to the family Ranunculacea, which is native to various regions of the world. In this chapter, we discuss the antiviral activities of N. sativa against critical viral pathogens, focusing more on the SARS-CoV-2 virus, the etiologic agent of the current unparalleled coronavirus disease (COVID-19) pandemic.
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Monoterpenes have been identifi ed as responsible of important therapeutic effects of plant-extracts. In this work, we try to compare the cytotoxic effect of six monoterpenes (carvacrol, thymol, carveol, carvone, eugenol and isopulegol) as well as their molecular mechanisms. The in vitro antitumor activity of the tested products, evaluated against fi ve tumor cell lines, show that the carvacrol is the most cytotoxic monoterpene. The investigation of an eventual synergistic effect of the six natural monoterpenes with two anticancer drugs revealed that there is a signifi cant synergy between them (p<5%). On the other hand, the effect of the tested products on cell cycle progression was examined by fl ow cytometry after DNA staining in order to investigate the molecular mechanism of their cytotoxic activity. The results revealed that carvacrol and carveol stopped the cell cycle progression in S phase; however, thymol and isopulegol stopped it in G0/G1 phase. Regarding carvone and eugenol, no effect on cell cycle was observed.
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Mexican oregano (Lippia graveolens) is a plant found in Mexico and Central America that is traditionally used as a medicinal herb. In the present study, we investigated the antiviral activity of the essential oil of Mexican oregano and its major component, carvacrol, against different human and animal viruses. The MTT test (3-4,5-dimethythiazol-2yl)-2,5-diphenyl tetrazolium bromide) was conducted to determine the selectivity index (SI) of the essential oil, which was equal to 13.1, 7.4, 10.8, 9.7, and 7.2 for acyclovir-resistant herpes simplex virus type 1 (ACVR-HHV-1), acyclovir-sensitive HHV-1, human respiratory syncytial virus (HRSV), bovine herpesvirus type 2 (BoHV-2), and bovine viral diarrhoea virus (BVDV), respectively. The human rotavirus (RV) and BoHV-1 and 5 were not inhibited by the essential oil. Carvacrol alone exhibited high antiviral activity against RV with a SI of 33, but it was less efficient than the oil for the other viruses. Thus, Mexican oregano oil and its main component, carvacrol, are able to inhibit different human and animal viruses in vitro. Specifically, the antiviral effects of Mexican oregano oil on ACVR-HHV-1 and HRSV and of carvacrol on RV justify more detailed studies.
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Carvacrol is a phenolic monoterpen found in Thyme plant which is used as a source of flavour in food. The aim of this study was to investigate apoptotic effects of carvacrol on H-ras transformed 5RP7 and N-ras transformed CO25 cell lines and possibilities of carvacrol as being a chemoterapeutic drug. The data was shown that carvacrol has cytotoxic effects on both cell lines upon time- and concentrations. IC50 values were determined 0.04 mg/mL for 5RP7 and 0.1 mg/mL for CO25 cell lines. Depending on the IC50 values, although carvacrol induced morphological changes on both cell types, mobility of phosphatidilserine localisation analysed by flow cytometry was only detected on 5RP7 cells. Beside, DNA laddering which is the late apoptotic determinant was seen on H-ras transformed cells but not on N-ras transformed cells at concentration IC50 value and below. These results indicated that H-ras transformed cells are more sensitive to carvacrol than N-ras tranformed cells. This investigation suggests the possibility that carvacrol may find application in cancer therapy as an antineoplastic drug.
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