Alavinezhad A, Hedayati M, Boskabady MH.
2017. The effect of Zataria multiflora and
carvacrol on wheezing, FEV1 and plasma
levels of nitrite in asthmatic patients.
Avicenna J Phytomed, 7: 531-541.
Amin F, Memarzia A, Kazerani HR,
Boskabady MH. 2020a. Carvacrol and
Zataria multiflora influenced the PPARγ
agonist effects on systemic inflammation
and oxidative stress induced by inhaled
paraquat in rat. Iran J Basic Med Sci, 23:
930-936.
Amin F, Memarzia A, Rad HK, Kazerani HR,
Boskabady MH. 2021. Carvacrol and
PPARγ agonist, pioglitazone, affects
inhaled paraquat-induced lung injury in
rats. Sci Rep, 11: 8129.
Amin F, Roohbakhsh A, Memarzia A, Kazerani
HR, Boskabady MH. 2020b. Paraquatinduced systemic inflammation and
increased oxidative markers in rats
improved by Zataria multiflora extract and
carvacrol. Avicenna J Phytomed, 10: 513-
522.
Amiresmaeili A, Roohollahi S, Mostafavi A,
Askari N. 2018. Effects of oregano
essential oil on brain TLR4 and TLR2
gene expression and depressive-like
behavior in a rat model. Res Pharm Sci, 13:
130-141.
Arab Z, Hosseini M, Mashayekhi F,
Anaeigoudari A. 2020. Zataria multiflora
extract reverses lipopolysaccharideinduced anxiety and depression behaviors
in rats. Avicenna J Phytomed, 10: 78-88.
Aryanezhad M, Abdi M, Amini S, Hassanzadeh
K, Valadbeigi E, Rahimi K, Izadpanah E,
Moloudi MR. 2021. Cinnamomum
zeylanicum extract has antidepressant-like
effects by increasing brain-derived
neurotrophic factor (BDNF) and its
receptor in prefrontal cortex of rats.
Avicenna J Phytomed, 11: 302-313.
Azizi-Malekabadi H, Hosseini M, Pourganji M,
Zabihi H, Saeedjalali M, Anaeigoudari A.
2015a. Deletion of ovarian hormones
induces a sickness behavior in rats
comparable to the effect of
lipopolysaccharide. Neurol Res Int, 2015:
627642.
Azizi-Malekabadi H, Pourganji M, Zabihi H,
Saeedjalali M, Hosseini M. 2015b.
Tamoxifen antagonizes the effects of
ovarian hormones to induce anxiety and
depression-like behavior in rats. Arq
Neuropsiquiatr, 73: 132-139.
Bakhtiari-Dovvombaygi H, Izadi S, Zare
Moghaddam M, Hashemzehi M, Hosseini
M, Azhdari-Zarmehri H, Dinpanah H,
Beheshti F. 2021. Beneficial effects of
vitamin D on anxiety and depression-like
behaviors induced by unpredictable
chronic mild stress by suppression of brain
oxidative stress and neuroinflammation in
rats. Naunyn Schmiedebergs Arch
Pharmacol, 394: 655-667.
Beheshti F, Hashemzehi M, Hosseini M,
Marefati N, Memarpour S. 2020. Inducible
nitric oxide synthase plays a role in
depression- and anxiety-like behaviors
chronically induced by lipopolysaccharide
in rats: Evidence from inflammation and
oxidative stress. Behav Brain Res, 392:
112720.
Boskabady MH, Jalali S, Yahyazadeh N,
Boskabady M. 2016. Carvacrol attenuates
serum levels of total protein,
phospholipase A2 and histamine in
asthmatic guinea pig. Avicenna J
Phytomed, 6: 636-642.
Cioanca O, Hritcu L, Mihasan M, Trifan A,
Hancianu M. 2014. Inhalation of coriander
volatile oil increased anxiolytic–
antidepressant-like behaviors and
decreased oxidative status in beta-amyloid
(1–42) rat model of Alzheimer's disease.
Physiol Behav, 131: 68-74.
Cunningham C. 2013. Microglia and
neurodegeneration: The role of systemic
inflammation. Glia, 61: 71-90.
Dantzer R, O'Connor JC, Freund GG, Johnson
RW, Kelley KW. 2008. From
inflammation to sickness and depression:
when the immune system subjugates the
brain. Nat Rev Neurosci, 9: 46-56.
Depino AM. 2015. Early prenatal exposure to
LPS results in anxiety-and depressionrelated behaviors in adulthood.
Neuroscience, 299: 56-65.
El-Gendy ZA, Ramadan A, El-Batran SA,
Ahmed RF, El-Marasy SA, Abd ElRahman SS, Youssef S. 2021. Carvacrol
hinders the progression of hepatic fibrosis
via targeting autotaxin and thioredoxin in
thioacetamide-induced liver fibrosis in rat.
Hum Exp Toxicol, 40: 2188-2201.
Furtado M, Katzman MA. 2015. Examining the
role of neuroinflammation in major
Salmani et al.
AJP, Vol. 12, No. 5, Sep-Oct 2022 524
depression. Psychiatry Res, 229: 27-36.
Ghorani V, Alavinezhad A, Rajabi O,
Boskabady MH. 2021a. Carvacrol
improves pulmonary function tests,
oxidant/antioxidant parameters and
cytokine levels in asthmatic patients: A
randomized, double-blind, clinical trial.
Phytomedicine, 85: 153539.
Ghorani V, Alavinezhad A, Rajabi O,
Mohammadpour AH, Boskabady MH.
2021b. Safety and tolerability of carvacrol
in healthy subjects: a phase I clinical study.
Drug Chem Toxicol, 44: 177-189.
Ghorani V, Boskabady M, Boskabady MH.
2019. Effect of carvacrol on pulmonary
function tests, and total and differential
white blood cell counts in healthy
volunteers: A randomized clinical trial.
Avicenna J Phytomed, 9: 134-142.
Hakimi Z, Salmani H, Marefati N, Arab Z,
Gholamnezhad Z, Beheshti F, Shafei MN,
Hosseini M. 2020. Protective effects of
carvacrol on brain tissue inflammation and
oxidative stress as well as learning and
memory in lipopolysaccharide-challenged
rats. Neurotox Res, 37: 965-976.
Hilakivi-Clarke LA, Wozniak KM, Durcan MJ,
Linnoila M. 1990. Behavior of
streptozotocin-diabetic mice in tests of
exploration, locomotion, anxiety,
depression and aggression. Physiol Behav,
48: 429-433.
Holmes C. 2013. Review: Systemic
inflammation and Alzheimer's disease.
Neuropathol Appl Neurobiol, 39: 51-68.
Hosseini M, Boskabady MH, Khazdair MR.
2021. Neuroprotective effects of
Coriandrum sativum and its constituent,
linalool: A review. Avicenna J Phytomed,
11: 436-450.
Hritcu L, Gorgan LD. 2014. Intranigral
lipopolysaccharide induced anxiety and
depression by altered BDNF mRNA
expression in rat hippocampus. Prog
Neuropsychopharmacol Biol Psychiatry,
51: 126-132.
Huang Y, Henry CJ, Dantzer R, Johnson RW,
Godbout JP. 2008. Exaggerated sickness
behavior and brain proinflammatory
cytokine expression in aged mice in
response to intracerebroventricular
lipopolysaccharide. Neurobiol Aging, 29:
1744-1753.
Ismail H, Mirza B. 2015. Evaluation of
analgesic, anti-inflammatory, antidepressant and anti-coagulant properties of
Lactuca sativa (CV. Grand Rapids) plant
tissues and cell suspension in rats. BMC
Complement Altern Med, 15: 199.
Khazdair MR, Alavinezhad A, Boskabady MH.
2018. Carvacrol ameliorates
haematological parameters,
oxidant/antioxidant biomarkers and
pulmonary function tests in patients with
sulphur mustard-induced lung disorders: A
randomized double-blind clinical trial. J
Clin Pharm Ther, 43: 664-674.
Khazdair MR, Boskabady MH. 2019a. A
double-blind, randomized, placebocontrolled clinical trial on the effect of
carvacrol on serum cytokine levels and
pulmonary function tests in sulfur mustard
induced lung injury. Cytokine, 113: 311-
318.
Khazdair MR, Boskabady MH. 2019b. The
effect of carvacrol on inflammatory
mediators and respiratory symptoms in
veterans exposed to sulfur mustard, a
randomized, placebo-controlled trial.
Respir Med, 150: 21-29.
Khazdair MR, Boskabady MH, Hosseini M,
Rezaee R, M. Tsatsakis A. 2015. The
effects of Crocus sativus (saffron) and its
constituents on nervous system: A review.
Avicenna J Phytomed, 5: 376-391.
Kianmehr M, Rezaee A, Mahmoudi M,
Ghorani V, Boskabady MH. 2019. T
helper cells subtypes and their cytokine
gene expression affected by carvacrol in
sensitized mice administered during
sensitization period. J Cell Biochem, 120:
5343-5354.
Kianmehr M, Rezaei A, Boskabady MH. 2016.
Effect of carvacrol on various cytokines
genes expression in splenocytes of
asthmatic mice. Iran J Basic Med Sci, 19:
402-410.
Kianmehr M, Rezaei A, Hosseini M, Khazdair
MR, Rezaee R, Askari VR, Boskabady
MH. 2017. Immunomodulatory effect of
characterized extract of Zataria multiflora
on Th(1), Th(2) and Th(17) in normal and
Th(2) polarization state. Food Chem
Toxicol, 99: 119-127.
Kohler-Forsberg O, Lydholm CN, Hjorthoj C,
Nordentoft M, Mors O, Benros ME. 2019.
Efficacy of anti-inflammatory treatment
on major depressive disorder or depressive
symptoms: meta-analysis of clinical trials.
Acta Psychiatr Scand, 139: 404-419.
Carvacrol improved brain consequences of LPS
AJP, Vol. 12, No. 5, Sep-Oct 2022 525
Landa P, Kokoska L, Pribylova M, Vanek T,
Marsik P. 2009. In vitro anti-inflammatory
activity of carvacrol: Inhibitory effect on
COX-2 catalyzed prostaglandin E 2
biosynthesisb. Arch Pharm Res, 32: 75-78.
Lima Mda S, Quintans-Júnior LJ, de Santana
WA, Martins Kaneto C, Pereira Soares
MB, Villarreal CF. 2013. Antiinflammatory effects of carvacrol:
evidence for a key role of interleukin-10.
Eur J Pharmacol, 699: 112-117.
Marefati N, Beheshti F, Memarpour S, Rezaei
M, Hosseini M. 2021. The effects of pretreatment with olibanum and its
constituent, boswellic acid on synaptic
plasticity impairments induced by
lipopolysaccharide in rats. Avicenna J
Phytomed, 11: 68-78.
Melo FH, Moura BA, de Sousa DP, de
Vasconcelos SM, Macedo DS, Fonteles
MM, Viana GS, de Sousa FC. 2011.
Antidepressant-like effect of carvacrol (5-
Isopropyl-2-methylphenol) in mice:
involvement of dopaminergic system.
Fundam Clin Pharmacol, 25: 362-367.
Melo FH, Venâncio ET, de Sousa DP, de
França Fonteles MM, de Vasconcelos SM,
Viana GS, de Sousa FC. 2010. Anxiolytic‐
like effect of Carvacrol (5‐isopropyl‐2‐
methylphenol) in mice: involvement with
GABAergic transmission. Fundam Clin
Pharmacol, 24: 437-443.
Miller AH, Maletic V, Raison CL. 2009.
Inflammation and its discontents: the role
of cytokines in the pathophysiology of
major depression. Biol Psychiatry, 65:
732-741.
Miller AH, Raison CL. 2015. The role of
inflammation in depression: from
evolutionary imperative to modern
treatment target. Nat Rev Immunol, 16:
22-34.
Mogenson GJ, Jones DL, Yim CY. 1980. From
motivation to action: functional interface
between the limbic system and the motor
system. Prog Neurobiol, 14: 69-97.
Mortazavi A, Mohammad Pour Kargar H,
Beheshti F, Anaeigoudari A, Vaezi G,
Hosseini M. 2021. The effects of carvacrol
on oxidative stress, inflammation, and
liver function indicators in a systemic
inflammation model induced by
lipopolysaccharide in rats. Int J Vitam
Nutr Res, 1-11.
Norouzi F, Abareshi A, Anaeigoudari A, Shafei
MN, Gholamnezhad Z, Saeedjalali M,
Mohebbati R, Hosseini M. 2016. The
effects of Nigella sativa on sickness
behavior induced by lipopolysaccharide in
male Wistar rats. Avicenna J Phytomed, 6:
104-116.
O'Connor JC, André C, Wang Y, Lawson MA,
Szegedi SS, Lestage J, Castanon N, Kelley
KW, Dantzer R. 2009. Interferon-γ and
tumor necrosis factor-α mediate the
upregulation of indoleamine 2, 3-
dioxygenase and the induction of
depressive-like behavior in mice in
response to bacillus Calmette-Guérin. J
Neurosci, 29: 4200-4209.
Patro G, Kumar Bhattamisra S, Kumar
Mohanty B. 2016. Effects of Mimosa
pudica L. leaves extract on anxiety,
depression and memory. Avicenna J
Phytomed, 6: 696-710.
Patterson SL. 2015. Immune dysregulation and
cognitive vulnerability in the aging brain:
Interactions of microglia, IL-1β, BDNF
and synaptic plasticity.
Neuropharmacology, 96: 11-18.
Pires LF, Costa LM, Silva OA, de Almeida AA,
Cerqueira GS, de Sousa DP, de Freitas
RM. 2013. Anxiolytic-like effects of
carvacryl acetate, a derivative of carvacrol,
in mice. Pharmacol Biochem Behav, 112:
42-48.
Puffenbarger RA, Boothe AC, Cabral GA.
2000. Cannabinoids inhibit LPS‐inducible
cytokine mRNA expression in rat
microglial cells. Glia, 29: 58-69.
Raison CL, Capuron L, Miller AH. 2006.
Cytokines sing the blues: inflammation
and the pathogenesis of depression. Trends
Immunol, 27: 24-31.
Roth J, Harre EM, Rummel C, Gerstberger R,
Hubschle T. 2004. Signaling the brain in
systemic inflammation: role of sensory
circumventricular organs. Front Biosci, 9:
290-300.
Salmani H, Hosseini M, Baghcheghi Y,
Moradi-Marjaneh R, Mokhtari-Zaer A.
2020. Losartan modulates brain
inflammation and improves mood
disorders and memory impairment induced
by innate immune activation: The role of
PPAR-γ activation. Cytokine, 125:
154860.
Samarghandian S, Farkhondeh T, Samini F.
2018. A review on possible therapeutic
effect of Nigella sativa and thymoquinone
Salmani et al.
AJP, Vol. 12, No. 5, Sep-Oct 2022 526
in neurodegenerative diseases. CNS
Neurol Disord Drug Targets, 17: 412-420.
Samarghandian S, Farkhondeh T, Samini F,
Borji A. 2016. Protective effects of
carvacrol against oxidative stress induced
by chronic stress in rat's brain, liver, and
kidney. Biochem Res Int, 2016: 2645237.
Seibenhener ML, Wooten MC. 2015. Use of the
open field maze to measure locomotor and
anxiety-like behavior in mice. J Vis Exp,
e52434.
Silva FV. Guimarães AG, Silva ER, SousaNeto BP, Machado FD, Quintans-Júnior
LJ, Arcanjo DD, Oliveira FA, Oliveira RC.
2012. Anti-inflammatory and anti-ulcer
activities of carvacrol, a monoterpene
present in the essential oil of oregano. J
Med Food, 15: 984-991.
Silva N, Fernandes JA. 2010. Biological
properties of medicinal plants: a review of
their antimicrobial activity. J Venom Anim
Toxins incl Trop Dis, 16: 402-413.
Swiergiel AH, Dunn AJ. 2007. Effects of
interleukin-1beta and lipopolysaccharide
on behavior of mice in the elevated plusmaze and open field tests. Pharmacol
Biochem Behav, 86: 651-659.
Taksande BG, Chopde CT, Umekar MJ,
Kotagale NR. 2015. Agmatine attenuates
lipopolysaccharide induced anorexia and
sickness behavior in rats. Pharmacol
Biochem Behav, 132: 108-114.
Teeling JL, Perry VH. 2009. Systemic infection
and inflammation in acute CNS injury and
chronic neurodegeneration: Underlying
mechanisms. Neuroscience, 158: 1062-
1073.
Thomson CA, McColl A, Cavanagh J, Graham
GJ. 2014. Peripheral inflammation is
associated with remote global gene
expression changes in the brain. J
Neuroinflammation, 11: 73.
Yang C, Wardenaar KJ, Bosker FJ, Li J,
Schoevers RA. 2019. Inflammatory
markers and treatment outcome in
treatment resistant depression: A
systematic review. J Affect Disord, 257:
640-649.
Yanishlieva NV, Marinova EM, Gordon MH,
Raneva VG. 1999. Antioxidant activity
and mechanism of action of thymol and
carvacrol in two lipid systems. Food
Chem, 64: 59-66.
Yin QH, Yan FX, Zu XY, Wu YH, Wu XP,
Liao MC, Deng SW, Yin LL, Zhuang YZ.
2012. Anti-proliferative and pro-apoptotic
effect of carvacrol on human
hepatocellular carcinoma cell line HepG2. Cytotechnology, 64: 43-51.
Zhao Y, Shang P, Wang M, Xie M, Liu J. 2020.
Neuroprotective effects of fluoxetine
against chronic stress-induced neural
inflammation and apoptosis: Involvement
of the p38 activity. Front Physiol, 11: 351.
Zung WW. 1965. A self-rating depression
scale. Arch Gen Psychiatry, 12: 63-70.