Pelargonidin Improves Passive Avoidance Task Performance in a Rat Amyloid Beta25-35 Model of Alzheimer’s Disease Via Estrogen Receptor Independent Pathways
Alzheimer’s disease (AD) is a disorder with multiple pathophysiological causes, destructive outcomes, and no available definitive cure. Pelargonidin (Pel), an anthocyanin derivative, is an estrogen receptor agonist with little estrogen side effects. This study was designed to assess Pel memory enhancing effects on the a rat Amyloid Beta25-35 (Aβ) intrahippocampal microinjections model of AD in the passive avoidance task performance paradigm and further evaluate the potential estrogen receptor role on the memory-evoking compound. Equally divided rats were assigned to 5 groups of sham, Aβ intrahippocampal microinjected, Pel pretreated (10 mg/kg; P.O), α estrogen antagonist intra-cerebrovascular (i.c.v.) microinjected, and β estrogen antagonist (i.c.v) microinjected animals. Intrahippocampal microinjections of Aβ were adopted to provoke AD model. Passive avoidance task test was also used to assess memory performance. Pel pretreatment prior to Aβ microinjections significantly improved step-through latency (P<0.001) in passive avoidance test. In α and β estrogen, antagonists received animals, passive avoidance task performance was not statistically changed (P=0.11 & P=0.41 respectively) compared to Pel pretreated and sham animals. Our results depicted that Pel improves Aβ induced memory dysfunction in passive avoidance test performance through estrogen receptor independently related pathways.
Alzheimer’s A. 2015 Alzheimer's disease facts and figures. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2015;11(3):332.
Querfurth HW, LaFerla FM. Alzheimer's Disease. New England Journal of Medicine 2010;362(4):329-44.
Bernal-Mondragon C, Rivas-Arancibia S, Kendrick KM, et al. Estradiol prevents olfactory dysfunction induced by A-beta 25-35 injection in hippocampus. BMC Neurosci 2013;14:104.
Hardy J, Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends Pharmacol Sci 1991;12(10):383-8.
Kumar A, Singh A, Ekavali. A review on Alzheimer's disease pathophysiology and its management: an update. Pharmacol Rep 2015;67(2):195-203.
Anand R, Gill KD, Mahdi AA. Therapeutics ofAlzheimer's disease: Past, present and future.Neuropharmacology 2014;76:27-50.
Hardy JA, Higgins GA. Alzheimer's disease: the amyloid cascade hypothesis. Science 1992;256(5054):184.
Krstic D, Knuesel I. The airbag problem–a potential culprit for bench-to-bedside translational efforts: relevance for Alzheimer’s disease. Acta Neuropathol Commun 2013;1:62.
Burke A, Hall GR, Yaari R, et al. Pharmacological Treatment of Cognitive Decline in Alzheimer’s Disease. Pocket Reference to Alzheimer's Disease Management: Springer; 2015. p. 35-40.
Dreiseitel A, Schreier P, Oehme A, et al. Inhibition of proteasome activity by anthocyanins and anthocyanidins. Biochem Biophys Res Commun 2008;372(1):57-61.
Paixão J, Dinis TC, Almeida LM. Dietary anthocyaninsprotect endothelial cells against peroxynitrite-induced mitochondrial apoptosis pathway and Bax nuclear translocation: an in vitro approach. Apoptosis 2011;16(10):976-89.
Bowen-Forbes CS, Zhang Y, Nair MG. Anthocyanincontent, antioxidant, anti-inflammatory and anticancerproperties of blackberry and raspberry fruits. Journal ofFood Composition and Analysis 2010;23(6):554-60.
Shindo M, Kasai T, Abe A, et al. Effects of dietary administration of plant-derived anthocyanin-rich colors to spontaneously hypertensive rats. Journal of nutritionalscience and vitaminology 2007;53(1):90-3.
Asgary S, RafieianKopaei M, Sahebkar A, et al. Antihyperglycemic and antihyperlipidemic effects of Vaccinium myrtillus fruit in experimentally induced diabetes (antidiabetic effect of Vaccinium myrtillus fruit). Journal of the Science of Food and Agriculture 2015.
Nabavi S, Habtemariam S, Daglia M, et al. Anthocyanins as a potential therapy for diabetic retinopathy. Curr MedChem 2015;22(1):51-8.
Kamiloglu S, Capanoglu E, Grootaert C, et al. Anthocyanin Absorption and Metabolism by HumanIntestinal Caco-2 Cells—A Review. International journal of molecular sciences 2015;16(9):21555-74.
Carkeet C, Clevidence BA, Novotny JA. Anthocyaninexcretion by humans increases linearly with increasing strawberry dose. The Journal of nutrition 2008;138(5):897-902.
Spencer JP. Food for thought: the role of dietary flavonoids in enhancing human memory, learning and neuro-cognitive performance. Proceedings of the Nutrition Society 2008;67(02):238-52.
Abraham SK, Schupp N, Schmid U, et al. Antigenotoxic effects of the phytoestrogen pelargonidin chloride and the polyphenol chlorogenic acid. Molecular nutrition & food research 2007;51(7):880-7.
Roghani M, Niknam A, Jalali-Nadoushan MR, et al. Oral pelargonidin exerts dose-dependent neuroprotection in 6- hydroxydopamine rat model of hemi-parkinsonism. Brain research bulletin 2010;82(5):279-83.
Mirshekar M, Roghani M, Khalili M, et al. Chronic oralpelargonidin alleviates streptozotocin-induced diabetic neuropathic hyperalgesia in rat: involvement of oxidative stress. Iranian Biomedical Journal 2010;14(1-2):33.
Rechner AR, Kroner C. Anthocyanins and colonic metabolites of dietary polyphenols inhibit platelet function. Thrombosis research 2005;116(4):327-34.
Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates: Hard Cover Edition: Elsevier Science & Technology Books; 2007.
Dhandapani KM, Brann DW. Protective effects of estrogen and selective estrogen receptor modulators in the brain. Biology of reproduction 2002;67(5):1379-85.
Chakrabarti M, Haque A, Banik NL, et al. Estrogen receptor agonists for attenuation of neuroinflammation and neurodegeneration. Brain Res Bull 2014;109C:22-31.
Jefremov V, Rakitin A, Mahlapuu R, et al. 17βOestradiol Stimulation of GProteins in Aged and Alzheimer’s Human Brain: Comparison with Phytoestrogens. Journal of neuroendocrinology 2008;20(5):587-96.
Spencer JP, Vafeiadou K, Williams RJ, et al. Neuroinflammation: modulation by flavonoids and mechanisms of action. Mol Aspects Med 2012;33(1):83-97.
Hidalgo M, Martin-Santamaria S, Recio I, et al. Potential anti-inflammatory, anti-adhesive, anti/estrogenic, and angiotensin-converting enzyme inhibitory activities of anthocyanins and their gut metabolites. Genes & nutrition 2012:1-12.
Hämäläinen M, Nieminen R, Vuorela P, et al. Antiinflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-κ B activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-κ B activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediators of inflammation 2007;2007.
Kruger MJ, Davies N, Myburgh KH, et al. Proanthocyanidins, anthocyanins and cardiovascular diseases. Food Research International 2014;59:41-52.
Spencer JP, Crozier A. Flavonoids and related compounds: Bioavailability and Function: CRC Press; 2012.
Fader AJ, Johnson PE, Dohanich GP. Estrogen improves working but not reference memory and prevents amnestic effects of scopolamine on a radial-arm maze. Pharmacology Biochemistry and Behavior1999;62(4):711-7.
Williams RJ, Spencer JP. Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease. Free Radical Biology and Medicine 2012;52(1):35-45.