The effects of Artemisia absinthium L. on scopolamine-induced learning and memory impairment and brain tissue oxidative damage in adult rats

Document Type : Original Research Article


1 Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Physiology and Medical Physics, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran

3 Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran

4 Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

5 Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran

6 Psychiatry and Behavioral Sciences Research Center, Mashhad Universityof Medical Sciences, Mashhad, Iran


Objective: The present study examined the effects of Artemisia absinthium L. on scopolamine-induced memory dysfunction and brain tissue oxidative damage in rats.
Materials and Methods: Fifty rats were used in five groups: Control: received dimethyl sulfoxide (DMSO)/saline, Scopolamine: scopolamine (2 mg/kg) was administered along with DMSO/saline, and Scopolamine-Ext 50, Scopolamine-Ext 100, and Scopolamine-Ext 200 groups: A. absinthium hydroalcoholic extract 50, 100 and 200 mg/kg were administered before scopolamine. The Morris water maze (MWM) and passive avoidance (PA) tasks were used for assessment of behavioral parameters. Malondialdehyde (MDA), nitric oxide (NO) metabolites, total thiol, catalase (CAT), and superoxide dismutase (SOD) were measured in the cortex and hippocampus.
Results: A. absinthium decreased the delay time and distance traveled to reach the platform in the MWM test (p<0.05-p<0.001). Besides, the extract increased the delay time to pass in the dark and the light time while decreasing the number of entrances and the dark time in the PA task (p<0.05-p<0.001). In biochemical assessments, A. absinthium attenuated NO metabolites (p<0.001) and MDA (p<0.05- p<0.001) while enhanced total thiol (p<0.001), CAT and SOD (both p<0.05-p<0.001).
Conclusion: This study revealed that A. absinthium improved memory and learning impairment and brain tissue oxidative damage in scopolamine-treated rats. 


Abareshi A, Anaeigoudari A, Norouzi F,
Marefati N, Beheshti F, Saeedjalali M,
Hosseini M. 2019. The effects of captopril
on lipopolysaccharide-induced sickness
behaviors in rats. Vet Res Forum, 10: 199-
Akbari HR, Beheshti F, Sadeghnia H, Bafadam
S, Baghcheghi Y, Hosseini M. 2019. The
effects of captopril on learning and memory
impairment induced by scopolamine in rats:
anti-oxidative effects. Physiol Pharmacol,
23: 91-100.
Amat N, Upur H, Blažeković B. 2010. In vivo
hepatoprotective activity of the aqueous
extract of Artemisia absinthium L. against
chemically and immunologically induced
liver injuries in mice. J Ethnopharmacol,
131: 478-484.
Amel B, Omar K, Faiza F, Miloud S,
Abdelkader A. 2016. Behvior and glutamate
transaminase changes in rat exposed to lead
and treated by wordwood extract. Int J
Pharm Pharm, 8: 208-213.
Anaeigoudari A, Soukhtanloo M, Reisi P,
Beheshti F, Hosseini M. 2016. Inducible
nitric oxide inhibitor aminoguanidine,
ameliorates deleterious effects of
lipopolysaccharide on memory and long
term potentiation in rat. Life Sci, 158: 22-30.
Babaei R, Javadi-Paydar M, Sharifian M,
Mahdavian S, Almasi-Nasrabadi M,
Norouzi A, Dehpour AR. 2012.
Involvement of nitric oxide in pioglitazone
memory improvement in morphine-induced
memory impaired mice. Pharmacol
Rahimi et al.
AJP, Vol. 13, No. 1, Jan-Feb 2023 82
Biochem Behav, 103: 313-321.
Bargi R, Asgharzadeh F, Beheshti F, Hosseini
M, Sadeghnia HR, Khazaei M. 2017. The
effects of thymoquinone on hippocampal
cytokine level, brain oxidative stress status
and memory deficits induced by
lipopolysaccharide in rats. Cytokine, 96:
Bastianetto S, Ramassamy C, Poirier J, Quirion
R. 1999. Dehydroepiandrosterone (DHEA)
protects hippocampal cells from oxidative
stress-induced damage. Mol Brain Res, 66,
Batiha GE-S, Olatunde A, El-Mleeh A, Hetta
HF, Al-Rejaie S, Alghamdi S, Zahoor M,
Beshbishy AM, Murata T, Zaragoza-Bastida
A, Rivero-Perez N. 2020. Bioactive
compounds, pharmacological actions, and
pharmacokinetics of wormwood (Artemisia
absinthium). Antibiotics (Basel), 9: 353.
Beheshti F, Akbari HR, Baghcheghi Y,
Mansouritorghabeh F, Mortazavi Sani SS,
Hosseini M. 2021. Beneficial effects of
angiotensin converting enzyme inhibition
on scopolamine-induced learning and
memory impairment in rats, the roles of
brain-derived neurotrophic factor, nitric
oxide and neuroinflammation. Clin Exp
Hypertens, 43: 505-515.
Bora KS, Sharma A. 2010. Neuroprotective
effect of Artemisia absinthium L. on focal
ischemia and reperfusion-induced cerebral
injury. J Ethnopharmacol, 129: 403-409.
Bora KS, Sharma A. 2010. Phytochemical and
pharmacological potential of Artemisia
absinthium Linn. and Artemisia asiatica
Nakai: a review. J Pharm Res, 3: 325-328.
Bora KS, Sharma A. 2011. Evaluation of
antioxidant and free-radical scavenging
potential of Artemisia absinthium. Pharm
Biol, 49: 1216-1223.
Budzynska B, Boguszewska-Czubara A, KrukSlomka M, Skalicka-Wozniak K, Michalak
A, Musik I, Biala G. 2015. Effects of
imperatorin on scopolamine-induced
cognitive impairment and oxidative stress in
mice. Psychopharmacology, 232: 931-942.
Deepa P, Bae HJ, Park H-B, Kim S-Y, Choi
JW, Kim DH, Liu XQ, Ryu JH, Park SJ.
2020. Dracocephalum moldavica attenuates
scopolamine-induced cognitive impairment
through activation of hippocampal ERKCREB signaling in mice. J Ethnopharmacol,
253: 112651.
Dvorkin-Camiel L, Whelan JS. 2008. Tropical
american plants in the treatment of
infectious diseases. J Diet Suppl, 5: 349-
Fukui K, Onodera K, Shinkai T, Suzuki S,
Urano S. 2001. Impairment of learning and
memory in rats caused by oxidative stress
and aging, and changes in antioxidative
defense systems. Ann N Y Acad Sci, 928:
Ghasemi S, Moradzadeh M, Hosseini M,
Beheshti F, Sadeghnia HR. 2019. Beneficial
effects of Urtica dioica on scopolamineinduced memory impairment in rats:
protection against acetylcholinesterase
activity and neuronal oxidative damage.
Drug Chem Toxicol, 42: 167-175.
Hadi A, Hossein N, Shirin P, Najmeh N,
Abolfazl M. 2014. Anti-inflammatory and
analgesic activities of Artemisia absinthium
and chemical composition of its essential
oil. Int J Pharm Sci Rev Res, 38: 237-244.
Hafez HS, Ghareeb DA, Saleh SR, Abady MM,
El Demellawy MA, Hussien H, AbdelMonem N. 2017. Neuroprotective effect of
ipriflavone against scopolamine-induced
memory impairment in rats.
Psychopharmacology, 234: 3037-3053.
Hakimi Z, Salmani H, Marefati N, Arab Z,
Gholamnezhad Z, Beheshti F, Shafei MN,
Hosseini M. 2019. 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.
Hallal N, Kharoubi O, Benyettou I, Tair K,
Ozaslan M, Aoues A. 2016. In vivo
amelioration of oxidative stress by
Artemisia absinthium L. administration on
mercuric chloride toxicity in brain regions. J
Biol Sci, 16: 167-177.
Hatziieremia S, Gray A, Ferro V, Paul A, Plevin
R. 2006. The effects of cardamonin on
lipopolysaccharide‐induced inflammatory
protein production and MAP kinase and
NFκB signalling pathways in
monocytes/macrophages. Br J Pharmacol,
149: 188-198.
Hosseini M, Anaeigoudari A, Beheshti F,
Soukhtanloo M, Nosratabadi R. 2018.
Protective effect against brain tissues
oxidative damage as a possible mechanism
for beneficial effects of L-arginine on
lipopolysaccharide induced memory
impairment in rats. Drug Chem Toxicol, 41:
Neuroprotective effects of Artemisia absinthium L.
AJP, Vol. 13, No. 1, Jan-Feb 2023 83
Hosseini M, Mohammadpour T, Karami R,
Rajaei Z, Reza Sadeghnia H, Soukhtanloo
M. 2015. Effects of the hydro-alcoholic
extract of Nigella sativa on scopolamineinduced spatial memory impairment in rats
and its possible mechanism. Chin J Integr
Med, 21: 438-444.
Ishola IO, Adamson FM, Adeyemi OO. 2017.
Ameliorative effect of kolaviron, a
biflavonoid complex from Garcinia kola
seeds against scopolamine-induced memory
impairment in rats: role of antioxidant
defense system. Metab Brain Dis, 32: 235-
Jafarian S, Ling KH, Hassan Z, Perimal‐Lewis
L, Sulaiman MR, Perimal EK. 2019. Effect
of zerumbone on scopolamine‐induced
memory impairment and anxiety‐like
behaviours in rats. ADTRCI, 5: 637-643.
Kamat PK, Kalani A, Rai S, Swarnkar S, Tota
S, Nath C, Tyagi N. 2016. Mechanism of
oxidative stress and synapse dysfunction in
the pathogenesis of Alzheimer’s disease:
understanding the therapeutics strategies.
Mol Neurobiol, 53: 648-661.
Karimi S, Hejazian SH, Alikhani V, Hosseini
M. 2015. The effects of tamoxifen on spatial
and nonspatial learning and memory
impairments induced by scopolamine and
the brain tissues oxidative damage in
ovariectomized rats. Adv Biomed Res, 4:
Karimi S, Hosseini M, Mahdian Z, Babazadeh
B. 2017. Protection against brain tissues
oxidative damage as a possible mechanism
for improving effects of soy on
Scopolamine-induced learning and memory
impairments in ovariectomized rats. Ann
Med Health Sci Res, 7: 166-172.
Kharoubi O, Benyamina A, Hallal N,
Benyattou I, Aoues A, Slimani M. 2016.
Aluminum induced the oxidative stress
modification and behavioral variation in rat.
Int J Prev Med, 2: 1-7.
Kim M-S, Lee DY, Lee J, Kim HW, Sung SH,
Han J-S, Jeon WK. 2018. Terminalia
chebula extract prevents scopolamineinduced amnesia via cholinergic modulation
and anti-oxidative effects in mice. BMC
Complement Altern Med, 18: 136.
Lee HG, Kim H, Oh WK, Yu KA, Choe YK,
Ahn JS, Kim DS, Kim HS, Dinarello CA,
Kim K, Yoon DY. 2004. Tetramethoxy
hydroxyflavone p7F downregulates
inflammatory mediators via the inhibition of
nuclear factor κB. Ann N Y Acad Sci, 1030:
Liu X, Kim DH, Kim JM, Park SJ, Cai M, Jang
DS, Ryu JH. 2012. The memoryameliorating effects of Artemisia princeps
var. orientalis against cholinergic
dysfunction in mice. Am J Chin Med, 40:
Mahmoudi M, Ebrahimzadeh M, Ansaroudi F,
Nabavi S, Nabavi S. 2009. Antidepressant
and antioxidant activities of Artemisia
absinthium L. at flowering stage. Afr J
Biotechnol, 8: 7170-7175.
Marefati N, Mokhtari-Zaer A, Beheshti F,
Karimi S, Mahdian Z, Khodamoradi M,
Hosseini M. 2019. The effects of soy on
scopolamine-induced spatial learning and
memory impairments are comparable to the
effects of estradiol. Horm Mol Biol Clin
Investig, 39.
Mohammadian A, Moradkhani S, Ataei S,
Shayesteh TH, Sedaghat M, Kheiripour N,
Ranjbar A. 2016. Antioxidative and
hepatoprotective effects of hydroalcoholic
extract of Artemisia absinthium L. in rat. J
HerbMed Pharmacol, 5: 29-32.
Mostafa NM. 2018. β-Amyrin rich Bombax
ceiba leaf extract with potential
neuroprotective activity against
scopolamine-induced memory impairment
in rats. Rec Nat Prod, 12: 480-492.
Msaada K, Salem N, Bachrouch O, Bousselmi
S, Tammar S, Alfaify A, Al Sane K, Ben
Ammar W, Azeiz S, Haj Brahim A,
Hammami M, Selmi S. 2015. Chemical
composition and antioxidant and
antimicrobial activities of wormwood
(Artemisia absinthium L.) essential oils and
phenolics. J Chem, 2015: 804658.
Ngoupaye GT, Pahaye DB, Ngondi J, Moto
FCO, Bum EN. 2017. Gladiolus dalenii
lyophilisate reverses scopolamine-induced
amnesia and reduces oxidative stress in rat
brain. Biomed Pharmacother, 91: 350-357.
Parihar M, Chaudhary M, Shetty R, Hemnani T.
2004. Susceptibility of hippocampus and
cerebral cortex to oxidative damage in
streptozotocin treated mice: prevention by
extracts of Withania somnifera and Aloe
vera. J Clin Neurosci, 11: 397-402.
Postu PA, Sadiki FZ, El Idrissi M, Cioanca O,
Trifan A, Hancianu M, Hritcu L. 2019.
Pinus halepensis essential oil attenuates the
toxic Alzheimer’s amyloid beta (1-42)-
induced memory impairment and oxidative
Rahimi et al.
AJP, Vol. 13, No. 1, Jan-Feb 2023 84
stress in the rat hippocampus. Biomed
Pharmacother, 112: 108673.
Rabiei Z, Setorki M. 2018. Effect of
hydroalcoholic Echium amoenum extract on
scopolamine-induced learning and memory
impairment in rats. Pharm Biol, 56: 672-
Rabiei Z, Setorki M. 2020. Effects of ethanolic
extract of Artemisia persica on
scopolamine-induced cognitive impairment
and anxiety in rats. J Medicinal Plants, 1:
Rahnama S, Rabiei Z, Alibabaei Z, Mokhtari S,
Rafieian-Kopaei M, Deris F. 2015. Antiamnesic activity of Citrus aurantium flowers
extract against scopolamine-induced
memory impairments in rats. Neurol Sci, 36:
Rakhshandeh H, Heidari A, Pourbagher-Shahri
AM, Rashidi R, Forouzanfar F. 2021.
Hypnotic effect of A. absinthium
hydroalcoholic extract in pentobarbitaltreated mice. Neurol Res Int, 2021:
Rashidi R, Ghorbani A, Rakhshandeh H,
Mousavi SH. 2020. Protective effect of
Artemisia absinthium on 6-
hydroxydopamine-induced toxicity in SHSY5Y cell line. Avicenna J Phytomed, 11:
Rivas-Arancibia S, Guevara-Guzmán R,
López-Vidal Y, Rodríguez-Martínez E,
Zanardo-Gomes M, Angoa-Pérez M,
Raisman-Vozari R. 2010. Oxidative stress
caused by ozone exposure induces loss of
brain repair in the hippocampus of adult rats.
Toxicol Sci, 113: 187-197.
Sodhi RK, Jaggi AS, Singh N. 2014. Animal
models of dementia and cognitive
dysfunction. Life Sci, 109: 73-86.
Upadhyay P, Sadhu A, Singh PK, Agrawal A,
Ilango K, Purohit S, Dubey GP. 2018.
Revalidation of the neuroprotective effects
of a United States patented polyherbal
formulation on scopolamine induced
learning and memory impairment in rats.
Biomed Pharmacother, 97: 1046-1052.
Zaki HF, Abd-El-Fattah MA, Attia AS. 2014.
Naringenin protects against scopolamineinduced dementia in rats. Bull Fac Pharm,
52: 15-25.
Zhang T, Kim MJ, Kim MJ, Wu X, Yang HJ,
Yuan H, Huang S, Yoon SM, Kim KN, Park
S. 2022. Long-term effect of porcine brain
enzyme hydrolysate intake on Scopolamineinduced memory impairment in rats. Int J
Mol Sci, 23: 3361.