Anderson AJ, Stoltzner S, Lai F, Su J, Nixon
RA. 2000. Morphological and biochemical
assessment of DNA damage and apoptosis
in Down syndrome and Alzheimer disease,
and effect of postmortem tissue archival on
TUNEL. Neurobiol Aging, 21: 511-524.
Berrios GE. 1990. Alzheimer's disease: a
conceptual history. Int J Geriatr Psychiatry,
5: 355-365.
Butterfield DA, Swomley AM, Sultana R.
2013. Amyloid beta-peptide (1-42)-induced
oxidative stress in Alzheimer disease:
importance in disease pathogenesis and
progression. Antioxid Redox Signal, 19:
823-835.
Cai Y, Li X, Pan Z, Zhu Y, Tuo J, Meng Q, Dai
G, Yang G, Pan Y. 2020. Anthocyanin
ameliorates hypoxia and ischemia induced
inflammation and apoptosis by increasing
autophagic flux in SH-SY5Y cells. Eur J
Pharmacol, 883: 173360.
Calabrese V, Bates TE, Stella AM. 2000. NO
synthase and NO-dependent signal
pathways in brain aging and
neurodegenerative disorders: the role of
oxidant/antioxidant balance. Neurochem
Res, 25: 1315-1341.
Chen Z, Zhong C. 2014. Oxidative stress in
Alzheimer's disease. Neurosci Bull, 30: 271-
281.
Corona G, Vauzour D. 2017. Neuroprotective
effects of phytochemicals in neurological
disorders. pp. 65, New York, John Wiley &
Sons.
Dringenberg HC. 2000. Alzheimer's disease:
more than a 'cholinergic disorder' - evidence
that cholinergic-monoaminergic
interactions contribute to EEG slowing and
dementia. Behav Brain Res, 115: 235-249.
Duarte LJ, Chaves VC, Nascimento M, Calvete
E, Li M, Ciraolo E, Ghigo A, Hirsch E,
Simoes CMO, Reginatto FH, Dalmarco EM.
2018. Molecular mechanism of action of
Pelargonidin-3-O-glucoside, the main
anthocyanin responsible for the antiinflammatory effect of strawberry fruits.
Food Chem, 247: 56-65.
Durán-González J, Michi ED, Elorza B, PerezCórdova MG, Pacheco-Otalora LF,
Touhami A, Paulson P, Perry G, Murray IV,
Colom LV. 2013. Amyloid β peptides
modify the expression of antioxidant repair
enzymes and a potassium channel in the
septohippocampal system. Neurobiol
Aging, 34: 2071-2076.
Ereminas G, Majiene D, Sidlauskas K, Jakstas
V, Ivanauskas L, Vaitiekaitis G, Liobikas J.
2017. Neuroprotective properties of
anthocyanidin glycosides against H2O2-
induced glial cell death are modulated by
their different stability and antioxidant
activity in vitro. Biomed Pharmacother, 94:
188-196.
Facchinetti R, Bronzuoli MR, Scuderi C. 2018.
An animal model of Alzheimer disease
based on the intrahippocampal injection of
amyloid beta-peptide (1-42). Methods Mol
Biol, 1727: 343-352.
Fang J. 2015. Classification of fruits based on
anthocyanin types and relevance to their
health effects. Nutrition, 31: 1301-1306.
Fares A, Borrmann D. 2018. Neurochemical
aspects of Alzheimer's disease and
movement disturbances: A theory of betaamyloid and tau-protein. Am J Alzheimers
Dis Other Demen, 33: 535-540.
Hashemi-Firouzi N, Komaki A, Soleimani Asl
S, Shahidi S. 2017. The effects of the 5-HT7
receptor on hippocampal long-term
potentiation and apoptosis in a rat model of
Alzheimer's disease. Brain Res Bull, 135:
85-91.
Jack Jr CR, Albert MS, Knopman DS,
McKhann GM, Sperling RA, Carrillo MC,
Thies B, Phelps CH. 2011. Introduction to
the recommendations from the National
Institute on Aging-Alzheimer's Association
workgroups on diagnostic guidelines for
Alzheimer's disease. Alzheimers Dement, 7:
257-262.
Karthi N, Karthiga A, Kalaiyarasu T, Stalin A,
Manju V, Singh SK, Cyril R, Lee SM. 2017.
Exploration of cell cycle regulation and
modulation of the DNA methylation
mechanism of pelargonidin: Insights from
the molecular modeling approach. Comput
Biol Chem, 70: 175-185.
Effect of pelargonidin on neuronal apoptosis in amyloid-beta treated-rats
AJP, Vol. 11, No. 4, Jul-Aug 2021 415
Karthick C, Nithiyanandan S, Essa MM,
Guillemin GJ, Jayachandran SK,
Anusuyadevi M. 2019. Time-dependent
effect of oligomeric amyloid-beta (1-42)-
induced hippocampal neurodegeneration in
rat model of Alzheimer's disease. Neurol
Res, 41: 139-150.
Khandelwal N, Abraham SK. 2014. Protective
effects of common anthocyanidins against
genotoxic damage induced by
chemotherapeutic drugs in mice. Planta
Med, 80:1278-1283.
Kim HY, Lee DK, Chung BR, Kim HV, Kim
Y. 2016. Intracerebroventricular injection of
amyloid-beta peptides in normal mice to
acutely induce Alzheimer-like cognitive
deficits. J Vis Exp, 109: 53308.
Lee HP, Zhu X, Casadesus G, Castellani RJ,
Nunomura A, Smith MA, Lee HG, Perry G.
2010. Antioxidant approaches for the
treatment of Alzheimer's disease. Expert
Rev Neurother, 10: 1201-1208.
Lovell MA, Markesbery WR. 2007. Oxidative
DNA damage in mild cognitive impairment
and late-stage Alzheimer's disease. Nucleic
Acids Res, 35: 7497-7504.
Mirshekar M, Roghani M, Khalili M,
Baluchnejadmojarad T, Moazzen SA. 2010.
Chronic oral pelargonidin alleviates
streptozotocin-induced diabetic neuropathic
hyperalgesia in rat: involvement of
oxidative stress. Iran Biomed J, 14: 33-39.
Mirshekar M, Roghani M, Khalili M,
Baluchnejadmojarad T. 2011. Chronic oral
pelargonidin alleviates learning and
memory disturbances in streptozotocin
diabetic rats. Iran J Pharm Res, 10: 569-575.
Paxinos G, Watson C. 1998. The rat brain in
stereotaxic coordinates. Academic, San
Diego.
Pohanka M. 2014. Alzheimer s disease and
oxidative stress: a review. Curr Med Chem,
21: 356-364.
Pourheydar B, Soleimani Asl S, Azimzadeh M,
Rezaei Moghadam A, Marzban A,
Mehdizadeh M. 2016. Neuroprotective
effects of bone marrow mesenchymal stem
cells on bilateral common carotid arteries
occlusion model of cerebral ischemia in rat.
Behav Neurol, 2016: 2964712.
Roghani M, Niknam A, Jalali-Nadoushan MR,
Kiasalari Z, Khalili M, Baluchnejadmojarad
T. 2010. Oral pelargonidin exerts dosedependent neuroprotection in 6-
hydroxydopamine rat model of hemiparkinsonism. Brain Res Bull, 82: 279-283.
Seo M, Kim H, Lee JH, Park JW. 2020.
Pelargonidin ameliorates acetaminopheninduced hepatotoxicity in mice by inhibiting
the ROS-induced inflammatory apoptotic
response. Biochimie, 168: 10-16.
Shahidi S, Asl SS, Komaki A, Hashemi-Firouzi
N. 2018. The effect of chronic stimulation of
serotonin receptor type 7 on recognition,
passive avoidance memory, hippocampal
long-term potentiation, and neuronal
apoptosis in the amyloid beta protein treated
rat. Psychopharmacology (Berl), 5: 1513-
1525.
Shen Y, He P, Zhong Z, McAllister C,
Lindholm K. 2006. Distinct destructive
signal pathways of neuronal death in
Alzheimer's disease. Trends Mol Med, 12:
574-579.
Shih PH, Yeh CT, Yen GC. 2005. Effects of
anthocyanidin on the inhibition of
proliferation and induction of apoptosis in
human gastric adenocarcinoma cells. Food
Chem Toxicol, 43: 1557-1566.
Sohanaki, H, Baluchnejadmojarad T, Nikbakht
F, Roghani M. 2016. Pelargonidin improves
memory deficit in amyloid beta 25-35 rat
model of Alzheimer's disease by inhibition
of glial activation, cholinesterase, and
oxidative stress. Biomed Pharmacother, 83:
85-91.
Asl SS, Bergen H, Ashtari N, Amiri S, Łos MJ,
Mehdizadeh M. 2019a. Pelargonidin
exhibits restoring effects against amyloid βinduced deficits in the hippocampus of male
rats. Med J Islam Repub Iran, 33: 135.
Asl SS, Łos MJ, Mehdizadeh M. 2019b.
Pelargonidin improves amyloid β-induced
deficits in the long-term potentiation in
hippocampus of male rats. Physiol
Pharmacol, 23: 296-301.
Sultana R, Perluigi M, Butterfield DA. 2006.
Protein oxidation and lipid peroxidation in
brain of subjects with Alzheimer's disease:
insights into mechanism of
neurodegeneration from redox proteomics.
Antioxid Redox Signal, 8: 2021-2037.
Swomley AM, Forster S, Keeney JT, Triplett J,
Zhang Z, Sultana R, Butterfield DA. 2014.
Abeta, oxidative stress in Alzheimer
disease: evidence based on proteomics
studies. Biochim Biophys Acta, 1842: 1248-
1257.
Pham-Huy LA, He H, Pham-Huy C. 2008. Free
radicals, antioxidants in disease and health.
Alisavari et al.
AJP, Vol. 11, No. 4, Jul-Aug 2021 416
Int J Biomed Sci, 4:89-96.
Wrolstad RE. 2004. Anthocyanin pigments—
Bioactivity and coloring properties. J Food
Sci, 69: 419-425.
Xu Y, Xie L, Xie J, Liu Y, Chen W. 2018.
Pelargonidin-3-O-rutinoside as a novel
alpha-glucosidase inhibitor for improving
postprandial hyperglycemia. Chem
Commun (Camb), 55: 39-42.
Youdim KA, Dobbie MS, Kuhnle G,
Proteggente AR, Abbott NJ, Rice‐Evans C.
2003. Interaction between flavonoids and
the blood-brain barrier: in vitro studies. J
Neurochem, 85: 180-192.
)