Assessment of the neuroprotective effect of Cocos nucifera L. oil on learning and behavior impairment in ovariectomized rats

Document Type : Original Research Article


1 Student Research Committee, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran

2 Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

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

4 Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran

5 Department of Clinical Biochemistry, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran



Objective: The current study aimed to investigate whether Cocos nucifera L. oil (CO) is effective on menopause-related memory dysfunction in ovariectomized (OVX) rats.
Materials and Methods: Fifty healthy female Wistar rats were randomly selected and classified into five groups as control, OVX rats, and three OVX groups of rats which received three different doses (100, 200, and 400 mg/kg/day) of CO for five consecutive weeks by gavage. To assess the effect of CO, neurobehavioral tests such as Morris water maze (MWM) and Passive avoidance (PA) were done and then the animals were sacrificed to remove cortical and hippocampal tissues for biochemical analysis.
Results: In both behavioral tests including MWM and PA, treatment with CO particularly two higher doses of 200, and 400 mg/kg demonstrated significant improvement in comparison with OVX group. Furthermore, antioxidant biomarkers such as total thiol content, catalase and superoxide dismutase (SOD) activities were significantly higher in the OVX-CO groups versus the OVX group. On the contrary, malondialdehyde (MDA) concentration as an oxidative stress biomarker was remarkably lower in the OVX-CO200 and 400 mg groups than the OVX group.
Conclusion: The present study demonstrated the significant improvement of CO on learning and memory impairment induced by ovariectomy. Although the exact mechanism needs further investigation, it might have occurred due to the anti-oxidative effect of CO.


Main Subjects

Aebi H, Wyss SR, Scherz B, Gross J. 1976.
Properties of erythrocyte catalase from
homozygotes and heterozygotes for Swisstype acatalasemia. Biochem Genet, 14:
Ahmadabady S, Beheshti F, Shahidpour F,
Khordad E, Hosseini M. 2021. A
protective effect of curcumin on
cardiovascular oxidative stress indicators in
systemic inflammation induced by
lipopolysaccharide in rats. Biochem
Biophys Rep, 25: 100908.
Ancelin M-L, Ritchie K. 2005. Lifelong
endocrine fluctuations and related cognitive
disorders. Curr Pharm Des, 11: 4229-4252.
Asiaei F, Fazel A, Rajabzadeh AA, Hosseini
M, Beheshti F, Seghatoleslam M. 2017.
Neuroprotective effects of Nigella sativa
extract upon the hippocampus in PTUinduced hypothyroidism juvenile rats: A
stereological study. Metab Brain Dis, 32:
Azizi-Malekabadi H, Abareshi A, Beheshti F,
Marefati N, Norouzi F, Soukhtanloo M,
Hosseini M. 2018. The effect of captopril
on inflammation-induced liver injury in
male rats. Toxin Rev, 39: 275-283.
Bargi R, Asgharzadeh F, Beheshti F, Hosseini
M, Farzadnia M, Khazaei M. 2017.
Cocos nucifera L. oil and memory in ovariectomized rats
AJP, Vol. 13, No. 6, Nov-Dec 2023 673
Thymoquinone protects the rat kidneys
against renal fibrosis. Res Pharm Sci, 12:
Beheshti F, Hosseini M, Hashemzehi M,
Soukhtanloo M, Khazaei M, Shafei MN.
2019. The effects of PPAR-γ agonist
pioglitazone on hippocampal cytokines,
brain-derived neurotrophic factor, memory
impairment, and oxidative stress status in
lipopolysaccharide-treated rats. Iran J Basic
Med Sci, 22: 940-948.
Chomchalow N. 2013. Curing incurable
Alzheimer’s Disease with medicinal plants.
AU J Tech, 16: 215-220.
Ciappolino V, Mazzocchi A, Enrico P, Syrén
M-L, Delvecchio G, Agostoni C,
Brambilla P. 2018. N-3 polyunsatured fatty
acids in menopausal transition: A
systematic review of depressive and
cognitive disorders with accompanying
vasomotor symptoms. Int J Mol Sci, 19:
DebMandal M, Mandal S. 2011. Coconut
(Cocos nucifera L.: Arecaceae): in health
promotion and disease prevention. Asian
Pac J Trop Med, 4: 241-247.
Delrobaei F, Fatemi I, Shamsizadeh A,
Allahtavakoli M. 2019. Ascorbic acid
attenuates cognitive impairment and brain
oxidative stress in ovariectomized mice.
Pharmacol Rep, 71: 133-138.
Feranil AB, Duazo PL, Kuzawa CW, Adair
LS. 2011. Coconut oil predicts a beneficial
lipid profile in pre-menopausal women in
the Philippines. Asia Pac J Clin Nutr, 20:
Ferreira JA, Santos JM, Breitkreitz MC,
Ferreira JMS, Lins PMP, Farias SC, de
Morais DR, Eberlin MN, Bottoli CBG.
2019. Characterization of the lipid profile
from coconut (Cocos nucifera L.) oil of
different varieties by electrospray
ionization mass spectrometry associated
with principal component analysis and
independent component analysis. Food Res
Int, 123: 189-197.
Gardner AS, Rahman IA, Lai CT, Hepworth
A, Trengove N, Hartmann PE, Geddes DT.
2017. Changes in fatty acid composition of
human milk in response to cold-like
symptoms in the lactating mother and
infant. Nutrients, 9: 1034.
Ghasemi S, Hosseini M, Feizpour A, Alipour
F, Sadeghi A, Vafaee F, Mohammadpour
T, Soukhtanloo M, Ebrahimzadeh Bideskan
A, Beheshti F. 2017. Beneficial effects of
garlic on learning and memory deficits and
brain tissue damages induced by lead
exposure during juvenile rat growth is
comparable to the effect of ascorbic acid.
Drug Chem Toxicol, 40: 206-214.
Hogervorst E, Bandelow S. 2009. Brain and
cognition. Is there any case for improving
cognitive function in menopausal women
using estrogen treatment? Minerva Ginecol,
61: 499-515.
Hojo Y, Hattori T-a, Enami T, Furukawa A,
Suzuki K, Ishii H-t, Mukai H, Morrison JH,
Janssen WGM, Kominami S, Harada N,
Kimoto T, Kawato S. 2004. Adult male rat
hippocampus synthesizes estradiol from
pregnenolone by cytochromes P45017α and
P450 aromatase localized in neurons. Proc
Natl Acad Sci USA, 101: 865-870.
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: 175-181.
Hosseini M, Sadeghnia HR, Salehabadi S,
Alavi H, Gorji A. 2009. The effect of Larginine and L-NAME on
pentylenetetrazole induced seizures in
ovariectomized rats, an in vivo study.
Seizure, 18: 695-698.
John J, Sapa NK, Sheenoy RR. 2020. Virgin
coconut oil ameliorates colchicine induced
cognitive dysfunction-A preclinical study.
Pharm Sci, 26: 1-12.
Kan H, Hu W, Wang Y, Wu W, Yin Y, Liang
Y, Wang C, Huang D, Li W. 2015.
NADPH oxidase-derived production of
reactive oxygen species is involved in
learning and memory impairments in 16-
month-old female rats. Mol Med Rep, 12:
Khazdair MR, Rajabi O, Balali-Mood M,
Beheshti F, Boskabady MH. 2018. The
effect of Zataria multiflora on pulmonary
function tests, hematological and
oxidant/antioxidant parameters in sulfur
mustard exposed veterans, a randomized
doubled-blind clinical trial. Environ
Toxicol Pharmacol, 58: 180-188.
Kirshner Z, Yao JK, Li J, Long T, Nelson D,
Gibbs R. 2020. Impact of estrogen receptor
agonists and model of menopause on
Balderan et al.
AJP, Vol. 13, No. 6, Nov-Dec 2023 674
enzymes involved in brain metabolism,
acetyl-CoA production and cholinergic
function. Life Sci, 256: 117975.
Kretz O, Fester L, Wehrenberg U, Zhou L,
Brauckmann S, Zhao S, Prange-Kiel J,
Naumann T, Jarry H, Frotscher M. 2004.
Hippocampal synapses depend on
hippocampal estrogen synthesis. J
Neurosci, 24: 5913-5921.
Laureles LR, Rodriguez FM, Reaño CE,
Santos GA, Laurena AC, Mendoza EMT.
2002. Variability in fatty acid and
triacylglycerol composition of the oil of
coconut (Cocos nucifera L.) hybrids and
their parentals. J Agric Food Chem, 50:
Luine VN. 2014. Estradiol and cognitive
function: past, present and future. Horm
Behav, 66: 602-618.
Madesh M, Balasubramanian K. 1998.
Microtiter plate assay for superoxide
dismutase using MTT reduction by
superoxide. Indian J Biochem Biophys, 35:
Monteiro SC, Matté C, Bavaresco CS, Netto
CA, Wyse AT. 2005. Vitamins E and C
pretreatment prevents ovariectomy-induced
memory deficits in water maze. Neurobiol
Learn Mem, 84: 192-199.
Moreau KL, Hildreth KL, Klawitter J,
Blatchford P, Kohrt WM. 2020. Decline in
endothelial function across the menopause
transition in healthy women is related to
decreased estradiol and increased oxidative
stress. Geroscience, 42: 1699-1714.
Pearson JN, Rowley S, Liang L-P, White AM,
Day BJ, Patel M. 2015. Reactive oxygen
species mediate cognitive deficits in
experimental temporal lobe epilepsy.
Neurobiol Dis, 82: 289-297.
Plastina P, Bonofiglio D, Vizza D, Fazio A,
Rovito D, Giordano C, Barone I, Catalano
S, Gabriele B. 2012. Identification of
bioactive constituents of Ziziphus jujube
fruit extracts exerting antiproliferative and
apoptotic effects in human breast cancer
cells. J Ethnopharmacol, 140: 325-332.
Pourganji M, Hosseini M, Soukhtanloo M,
Zabihi H, Hadjzadeh MA-r. 2014.
Protective role of endogenous ovarian
hormones against learning and memory
impairments and brain tissues oxidative
damage induced by lipopolysaccharide.
Iran. Red Crescent Med J, 16: e13954.
Radenahmad N, Saleh F, Sawangjaroen K,
Vongvatcharanon U, Subhadhirasakul P,
Rundorn W, Withyachumnarnkul B,
Connor JR. 2011. Young coconut juice, a
potential therapeutic agent that could
significantly reduce some pathologies
associated with Alzheimer's disease: novel
findings. Br J Nutr, 105: 738-746.
Savonenko A, Markowska A. 2003. The
cognitive effects of ovariectomy and
estrogen replacement are modulated by
aging. Neuroscience, 119: 821-830.
Sherwin BB. 2005. Estrogen and memory in
women: how can we reconcile the
findings? Horm Behav, 47: 371-375.
Talboom JS, Williams BJ, Baxley ER, West
SG, Bimonte-Nelson HA. 2008. Higher
levels of estradiol replacement correlate
with better spatial memory in surgically
menopausal young and middle-aged rats.
Neurobiol Learn Mem, 90: 155-163.
Vafaee F, Hosseini M, Sadeghinia HR,
Hadjzadeh MA-r, Soukhtanloo M,
Rahimi M. 2014. The effects of soy
extract on spatial learning and memory
damage induced by global ischemia in
ovariectomised rats. Malays J Med Sci,
21: 19-30.
Vargas KG, Milic J, Zaciragic A, Wen K-x,
Jaspers L, Nano J, Dhana K, Bramer WM,
Kraja B, van Beeck E. 2016. The
functions of estrogen receptor beta in the
female brain: A systematic review.
Maturitas, 93: 41-57.
Vedin I, Cederholm T, Freund-Levi Y, Basun
H, Garlind A, Irving GF, EriksdotterJönhagen M, Wahlund L-O, Dahlman I,
Palmblad J. 2012. Effects of DHA-rich n3 fatty acid supplementation on gene
expression in blood mononuclear
leukocytes: the OmegAD study. PloS
One, 7: e35425.
WĹ‚odarek D. 2019. Role of ketogenic diets in
neurodegenerative diseases (Alzheimer’s
disease and Parkinson’s disease).
Nutrients, 11: 169.
Zou L, Pande G, Akoh CC. 2016. Infant
formula fat analogs and human milk fat:
new focus on infant developmental needs.
Annu Rev Food Sci Technol, 7: 139-165.