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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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... Growing interest among researchers has focused on the utilization of plant-derived natural antioxidants, including curcuminoids, flavonoids, phenolics, xanthones, tannins, coumarins, lignans, and terpenoids (Kheradmand et al. 2021). Herbal products provide viable and cost-efficient options to conventional medical treatments, such as surgery and pharmaceutical therapy, in addressing male infertility (Alagawany et al. 2015). Due to their antioxidant phytochemical content, herbal drugs have been suggested by the European Association of Urology as a potential therapy to develop sperm quality by mitigating oxidative stress (Daghigh Kia et al. 2016). ...
... Carvacrol, a potent antioxidant with demonstrated antibacterial, antifungal, food preservative, and antiaging properties in mammals, exhibits significantly higher antioxidant action compared to many synthetic antioxidants (Suntres et al. 2015;Kaeidi et al. 2020). Additionally, carvacrol has been shown to exhibit strong antimutagenic and anticancer activities in previous studies (Alagawany et al. 2015;Shoorei et al. 2019). ...
... Free radicals or reactive oxygen species are created through cells during normal metabolism. Excessive accumulation of free radicals leads to tissue damage and impairment of many cellular functions (Alagawany et al. 2015). Our results indicated that the MDA level was increased, and TAC was decreased upon freezing semen compared to the fresh. ...
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Nowadays, the cryopreservation process can produce reactive oxygen species (ROS), which cause damage to the motility, cell membrane, and DNA integrity of sperm. This study is aimed at evaluating the impact of carvacrol, as a powerful antioxidant, on sperm features and improving oxidative stress throughout the cryopreservation procedure. In this prospective study, semen samples from 25 patients with asthenozoospermia were separated into three groups: fresh, freezing, and freezing + carvacrol (a dose of 100 µM). The subsequent parameters were evaluated using standard methods in all three groups: sperm motility according to WHO criteria, sperm morphology using Papanicolaou staining, sperm viability with eosin-nigrosin staining, DNA integrity with acridine orange staining, levels of antioxidant enzymes (catalase, glutathione, and superoxide dismutase), total antioxidant capacity (TAC), and malondialdehyde (MDA) using ELISA. Also, DNA fragmentation was analyzed by the SDFA kit, and mitochondrial membrane potential (MMP) was assessed by rhodamine staining. Average sperm viability, motility, mitochondrial membrane potentiality, integrity of sperm membrane, and antioxidant enzyme levels are meaningfully reduced in the freezing group in contrast to the control group. The freezing group showed a meaningful rise in the mean MDA levels and DNA fragmentation compared to the control group. In the freezing group supplemented with carvacrol, a meaningful rise could be visible in mean percentages of viability, motility, and antioxidant enzyme levels, whereas mean levels of MDA and DNA fragmentation meaningfully declined in contrast to the freezing group. The results demonstrate that carvacrol, a potent antioxidant, offers significant protection against the loss generated by the freeze–thaw procedure, thereby improving sperm quality.
... L. graveolens is enriched with a variety of flavonoids (pinocembrin, quercetin O-hexoside) (Lin et al., 2007;Du et al., 2018), and terpenes, such as thymol and carvacrol, which are the major phytochemical components of its EO (Reyes-Jurado et al., 2019). Additive, antioxidant, antibacterial, antifungal, analgesic, anti-inflammatory, anticancer, and antidiabetic properties of L. graveolens EO have been reported in the literature, among others (Alagawany et al., 2015;González-Trujano et al., 2017;Gutiérrez-Grijalva et 2 al., 2017). Extraction of EO by the industry generates large amounts of the total weight of the plant (Martínez-Natarén et al., 2013). ...
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Mexican oregano (Lippia graveolens Kunth) is one of the most important species worldwide due to its human health benefit properties and high economic value. Oregano leaves are primarily used for essential oil extraction, generating substantial agro-industrial waste known as bagasse (OB). It has been reported that OB still contains several bioactive compounds with high antioxidant activity. This study aimed to evaluate the extraction conditions to recover phenolic compounds and assess their antioxidant capacity in OB extracts obtained through ultrasound. A 3k Box-Behnken design was employed to explore the effects of temperature, mass/volume ratio, and [EtOH]. Total phenolic content and antioxidant capacity against DPPH· and ABTS·+ radicals were determined. The increase in temperature and m/v ratio promoted the extraction of phenolic compounds, with strong correlations to antioxidant activity by DPPH· (0.81) and ABTS·+ (0.82) assays. A quadratic effect by [EtOH] was observed, with a maximum value of 50% ethanol. The highest value of total phenolic content (35.66 mgGAE/gdm), and antioxidant capacity against DPPH· (100.94 mgTE/gdm) and ABTS (93.02 mgTE/gdm) radicals were achieved in treatment 13 (0.02 mg/mL, 50% EtOH, and 90°C). The OB is a potential source of bioactive compounds with potential applications in functional food development.
... In this research, YILMAZ et al. (2017) highlighted that the higher the dose of thymol and carvacrol added to the diet, the better the growth, including final weight and weight gain of the fish. The improvement in growth rate is possible because thymol and carvacrol can prevent free radicals and improve the gut microflora condition of the fish, which eventually improves the digestion coefficient and absorption of nutrient compounds to optimize the growth (Alagawany et al., 2015;Alagawany et al., 2021). However, slightly different from YILMAZ et al. (2017), our results showed that the addition of OEO contain with thymol and carvacrol at doses higher than 0.2% did not have a significant impact on the growth of pangasius fish, whether fed with the topdressing method or fed with experimental formulated feed. ...
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The production efficiency of striped catfish Pangasianodon hypophthalmus is very dependent on the quality of feed, which can increase the fish's growth rate and health condition. Thus, the aimed of this study was to investigate the effects of different levels of Oregano Essential Oil (OEO) contained with thymol and carvacrol, at the concentration level of 0.1, 0.2, and 0.4% OEO, which is applied using top-dressing method and included in feed formulation on the growth rate, body composition, digestive health and resistance of striped catfish P. hypophthalmus against the pathogenic bacteria Aeromonas hydrophila. The results of growth trials using top-dressing method for 122 days using formulated feed method for 70 days showed that the application of OEO yielded better growth than the control, with 0.2% OEO providing better growth performance than 0.1 and 0.4% OEO. The body composition analysis results also showed a better level of nutrient absorption in fish fed the OEO-based diet compared to the control. For the number of bacteria in the digestive tract, OEO supplementation can also significantly reduce the number of bacteria compared to fish-fed control feed. The challenge test results after the fish were given treatment feed for 24 days showed that the application of 0.1% OEO provided better protection against Aeromonas hydrophila. However, there was no significant difference with 0.2% OEO. The application of 0.2% OEO can be recommended to increase the efficiency and productivity of catfish cultivation.
... Carvacrol is a monoterpene phenol originally found in different varieties of Origanum, Thymus, and Satureja plants (Suntres et al. 2015). Carvacrol supplementation in animal feed is a valid strategy to promote gut health due to its antioxidant, antiinflammatory, and antimicrobial properties (Alagawany et al. 2015). MCFAs are molecules characterized by the presence of 6 to 12 carbon atoms (Ferronato and Prandini 2020). ...
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Microbial transformations of cyclic hydrocarbons have received much attention during the past three decades. Interest in the degradation of environmental pollutants as well as in applications of microorganisms in the catalysis of chemical reactions has stimulated research in this area. The metabolic pathways of various aromatics, cycloalkanes, and terpenes in different microorganisms have been elucidated, and the genetics of several of these routes have been clarified. The toxicity of these compounds to microorganisms is very important in the microbial degradation of hydrocarbons, but not many researchers have studied the mechanism of this toxic action. In this review, we present general ideas derived from the various reports mentioning toxic effects. Most importantly, lipophilic hydrocarbons accumulate in the membrane lipid bilayer, affecting the structural and functional properties of these membranes. As a result of accumulated hydrocarbon molecules, the membrane loses its integrity, and an increase in permeability to protons and ions has been observed in several instances. Consequently, dissipation of the proton motive force and impairment of intracellular pH homeostasis occur. In addition to the effects of lipophilic compounds on the lipid part of the membrane, proteins embedded in the membrane are affected. The effects on the membrane-embedded proteins probably result to a large extent from changes in the lipid environment; however, direct effects of lipophilic compounds on membrane proteins have also been observed. Finally, the effectiveness of changes in membrane lipid composition, modification of outer membrane lipopolysaccharide, altered cell wall constituents, and active excretion systems in reducing the membrane concentrations of lipophilic compounds is discussed. Also, the adaptations (e.g., increase in lipid ordering, change in lipid/protein ratio) that compensate for the changes in membrane structure are treated.
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Inhibition/modification of chemical carcinogenesis induced by benzo(a)pyrene in 496 male Wistar rats by treatment with ascorbic acid alone or in combination with α-tocopherol was investigated in this study. The carcinogenic and anticarcinogenic potencies of substances used were calculated by using the animals mean survival time from each studied group. It was proven that ascorbic acid exerts an anticarcinogenic potency of 7.2 units; its combination with α-tocopherol highly enhances the anticarcinogenic potency to 20.1 units. A statistically significant difference was found between the control group and the animal group treated with ascorbic acid as well as between the control group and the group of animals treated with the combination of ascorbic acid/α-tocopherol. Furthermore, a statistically significant difference regarding the mean survival time in days was found between the animal group treated with ascorbic acid alone and the other animal group treated with the ascorbic acid/α-tocopherol combination (p < 0.001). In conclusion, antioxidants like ascorbic acid and α-tocopherol may inhibit or modify chemical carcinogenesis induced by benzo(a)pyrene.
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One hundred eighty newly weaned pigs were used to investigate effects of feeding organic acids and herbal extracts on growth performance, gut morphology and microbiota, and immune response in newly weaned pigs during a 4-wk period. There were five dietary treatments: control, Acid 1 (acetic, propionic, phosphoric and citric acid; 1.1% inclusion), Acid 2 (Acid 1 + 1.0% lactic acid), herbal extracts (0.75% inclusion; containing cinnamon, thyme and oregano extract), and antibiotic (110 ppm lincomycin). As compared to the control, pigs on antibiotic and Acid 2 showed higher (P < 0.05) ADG only during week 2 post-weaning, whereas pigs on herbal extract showed lower (P < 0.05) ADG only during week 3 post-weaning. Fecal coliform counts were lower (P < 0.08) in pigs on Acid 1 and 2 on day 4 post-weaning and in pigs on antibiotic and herbal extract on day 14 post-weaning. Fecal lactobacilli counts were lower (P < 0.05) in pigs on antibiotic on day 14 post-weaning. Based on PCR-DGGE, treatment influenced the composition of gut microbiota. The pH of the colon was lower (P < 0.05) in pigs on acid treatments and serum IgG was lower (P < 0.05) in pigs on antibiotic. Dietary treatment did not affect (P > 0.10) intestinal morphology. These results show that the inclusion of antibiotic in the diet reduced the proliferation of both potentially harmful coliform bacteria and potentially beneficial lactobacilli in the pig's gut, while herbal extract and organic acids appeared to reduce the proliferation of coliform bacteria. Blends of organic acids can serve as an alternative to in-feed antibiotics during the first few weeks post-weaning for pigs.
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The major goals of this study were to determine the impact of sugar beet pulp (SBP) levels and Avizyme® 1500 (xylanase, protease and amylase) enzyme addition on productive and reproductive performance as well as egg quality, apparent digestibility of nutrients and nitrogen balance in laying Japanese quail from 12 to 20 wks of age. The experimental design consisted of a 3 × 3 factorial arrangement with 3 levels of SBP (0, 20 and 40 g/ kg diet) and 3 concentrations of avizyme (0, 1 and 2 g/ kg diet). There were no differences in feed consumption, feed conversion ratio, egg number, egg weight and egg mass due to treatments. Final body weight was significantly (P≤0.01) decreased by increasing SBP levels. Increasing SBP level from 20 to 40g/kg in laying quails diet led to significant reduction in fertility percentage by 2.67 and 7.01 and 4.60% during periods 12 - 16, 16 - 20 and 12-20 wks of age, respectively. Hatchability percentages (from fertile eggs) elevated gradually with decreasing SBP level in the diets, during the overall period. Different levels of SBP and avizyme or their interaction insignificantly affected external and internal egg quality of laying quails during the overall experimental period (12-20 wks of age). Meanwhile, the different levels of SBP had a significant effect on all digestion coefficients in of nutrients except for nitrogen (N) digestibility. The N consumption (g/d), N in egg (g/d), N excretion (g/d), N fecal: N intake and N retention were not significantly affected either by SBP inclusion or avizyme supplementation. The overall results indicated that, inclusion of SBP and avizyme in quail diets did not affect productive performance, egg quality criteria and nitrogen balance, but reproductive parameters and nutrient digestibilities were statistically decreased with increasing SBP up to 40 g/kg diet throughout the overall period (12 to 20 wks of age).
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The present study was planned to evaluate the effects of turmeric (Curcuma longa) for protection against alterations resulted from exposure to endosulfan in broiler chicks. A total of 180 day old chicks were divided into 6 groups of 30 chicks with 3 replicates. First group was fed basal diet while the other five groups were fed basal diet supplemented with 5 g turmeric, 10 g turmeric, 30 mg endosulfan, 30 mg endosulfan plus 5 g turmeric and 30 mg endosulfan plus 10 g turmeric/kg diet during the experimental period. Growth performance, carcass traits, blood parameters, oxidative status and viability of the broilers chicks were used as criteria of response. The results showed that endosulfan significantly decreased the levels of Total Protein (TP), albumin (ALB), globulin (GLB), HDL-cholesterol, catalase (CAT), superoxide dismutase (SOD) activity and reduced glutathione (GSH) concentration but significantly increased albumin/globulin (A/G) ratio, total cholesterol (TCHO), LDL-cholesterol, triglyceride (TRG), malondialdehyde (MDA) concentration and hepatic transaminases (alanine amino-transferase, ALT and aspartate amino-transferase, AST) and exhibited different alterations to the hepatic structure in comparison with control and both turmeric groups. Dietary supplementation of turmeric at different levels could ameliorate these effects but not restored to control level. It is recommended that regular consumption of turmeric in the diet of broiler chicks provides a constant supply of potential antioxidants that could reduce these alterations.