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Current Drug Discovery Technologies

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ISSN (Print): 1570-1638
ISSN (Online): 1875-6220

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Research Article

Aqueous Extract of Cola nitida and Garcinia kola Synergistically Enhances Hippocampal-hypothalamic Glutamate and Na+ /K+ -ATPase Activity in Male Wistar Rats

Author(s): Kehinde S. Olaniyi*, Isaiah W. Sabinari, Adesola A. Oniyide, Nifesimi T. Akinnagbe, Toluwani B. Agunbiade and Oluwole O. Alese

Volume 19, Issue 1, 2022

Published on: 29 March, 2021

Article ID: e290321192495 Pages: 11

DOI: 10.2174/1570163818666210329102207

Price: $65

Abstract

Background: The incidence of cognitive decline has been proposed to rise exponentially in the coming years. Therapies targeting molecular pathways involved in the enhancement of memory and energy regulation could be a major breakthrough in the prevention or management of dementia in susceptible populations.

Objectives: This study investigated the effects of aqueous extracts of Cola nitida (AECONS) and Garcinia kola (AEGAK) on glutamate level and Na+/K+-ATPase activity in the hippocampus and hypothalamus of male Wistar rats.

Methods: Adult male Wistar rats (170-200) were randomly allotted into groups (n=5/group); control (distilled water p.o.), AECONS1 (200 mg/kg), AECONS2 (400 mg/kg), AEGAK1 (200 mg/kg), AEGAK2 (400 mg/kg), AECONS1+AEGAK1 and AECONS2+AEGAK2. The extract was prepared and the administration was done daily for 6 weeks.

Results and Discussion: Administration of AECONS or AEGAK increased plasma, hippocampal and hypothalamic glutamate, Na+/K+-ATPase activity, NO, SOD except hippocampal glutamate in AECONS1/AEGAK1, Na+/K+-ATPase activity and SOD in AEGAK1, hypothalamic glutamate and SOD in AECONS1 when compared with control. Besides, MDA level decreased in AEGAK2 and hippocampal but not hypothalamic MDA decreased in AEGAK1 compared with control. However, concomitant administration of AECONS and AEGAK enhanced plasma, hippocampal and hypothalamic biomarkers except hypothalamic MDA level. The present study demonstrates that AECONS and AEGAK synergistically enhance hippocampal and hypothalamic glutamate and Na+/K+- ATPase activity, which are accompanied by NO and SOD-dependent antioxidant enrichment.

Conclusion: These findings, therefore, suggest that AECONS+AEGAK could be a better therapeutic candidate in hippocampal-hypothalamic-related neurodegenerative diseases.

Keywords: Cola nitida, Garcinia kola, glutamate, hippocampus, hypothalamus, Neurocognitive derailment.

[1]
Tilvis RS, Kähönen-Väre MH, Jolkkonen J, Valvanne J, Pitkala KH, Strandberg TE. Predictors of cognitive decline and mortality of aged people over a 10-year period. J Gerontol A Biol Sci Med Sci 2004; 59(3): 268-74.
[http://dx.doi.org/10.1093/gerona/59.3.M268] [PMID: 15031312]
[2]
Zhang J, Chen C, Hua S, et al. An updated meta-analysis of cohort studies: Diabetes and risk of Alzheimer’s disease. Diabetes Res Clin Pract 2017; 124: 41-7.
[http://dx.doi.org/10.1016/j.diabres.2016.10.024] [PMID: 28088029]
[3]
Xia C, Zhu L, Shao W, et al. The effect of hippocampal cognitive impairment and XIAP on glucose and lipids metabolism in rats. Cell Physiol Biochem 2016; 38(2): 609-18.
[http://dx.doi.org/10.1159/000438654] [PMID: 26845572]
[4]
Guerchet M, Mayston R, Lloyd-Sherlock P, Prince M, Aboderin I, Akinyemi R, et al. Dementia in sub-saharan africa challenges and opportunities 2017.
[5]
Neumann KF, Rojo L, Navarrete LP, Farías G, Reyes P, Maccioni RB. Insulin resistance and Alzheimer’s disease: molecular links & clinical implications. Curr Alzheimer Res 2008; 5(5): 438-47.
[http://dx.doi.org/10.2174/156720508785908919] [PMID: 18855585]
[6]
Scuteri A, Nilsson PM, Tzourio C, Redon J, Laurent S. Microvascular brain damage with aging and hypertension: pathophysiological consideration and clinical implications. J Hypertens 2011; 29(8): 1469-77.
[http://dx.doi.org/10.1097/HJH.0b013e328347cc17] [PMID: 21577138]
[7]
Prakash A, Shur B, Kumar A. Naringin protects memory impairment and mitochondrial oxidative damage against aluminum-induced neurotoxicity in rats. Int J Neurosci 2013; 123(9): 636-45.
[http://dx.doi.org/10.3109/00207454.2013.785542] [PMID: 23510099]
[8]
Gallagher M, Nicolle MM. Animal models of normal aging: relationship between cognitive decline and markers in hippocampal circuitry. Behav Brain Res 1993; 57(2): 155-62.
[http://dx.doi.org/10.1016/0166-4328(93)90131-9] [PMID: 7906946]
[9]
Weinstock M, Luques L, Poltyrev T, Bejar C, Shoham S. Ladostigil prevents age-related glial activation and spatial memory deficits in rats. Neurobiol Aging 2011; 32(6): 1069-78.
[http://dx.doi.org/10.1016/j.neurobiolaging.2009.06.004] [PMID: 19625104]
[10]
Rodríguez JJ, Noristani HN, Verkhratsky A. The serotonergic system in ageing and Alzheimer’s disease. Prog Neurobiol 2012; 99(1): 15-41.
[http://dx.doi.org/10.1016/j.pneurobio.2012.06.010] [PMID: 22766041]
[11]
Velazquez R, Ash JA, Powers BE, et al. Maternal choline supplementation improves spatial learning and adult hippocampal neurogenesis in the Ts65Dn mouse model of Down syndrome. Neurobiol Dis 2013; 58: 92-101.
[http://dx.doi.org/10.1016/j.nbd.2013.04.016] [PMID: 23643842]
[12]
Dayer AG, Ford AA, Cleaver KM, Yassaee M, Cameron HA. Short-term and long-term survival of new neurons in the rat dentate gyrus. J Comp Neurol 2003; 460(4): 563-72.
[http://dx.doi.org/10.1002/cne.10675] [PMID: 12717714]
[13]
Abrous DN, Koehl M, Le Moal M. Adult neurogenesis: from precursors to network and physiology. Physiol Rev 2005; 85(2): 523-69.
[http://dx.doi.org/10.1152/physrev.00055.2003] [PMID: 15788705]
[14]
Yan BC, Park JH, Chen BH, et al. Long-term administration of scopolamine interferes with nerve cell proliferation, differentiation and migration in adult mouse hippocampal dentate gyrus, but it does not induce cell death. Neural Regen Res 2014; 9(19): 1731-9.
[http://dx.doi.org/10.4103/1673-5374.143415] [PMID: 25422633]
[15]
Haam J, Yakel JL. Cholinergic modulation of the hippocampal region and memory function. J Neurochem 2017; 142(Suppl. 2): 111-21.
[http://dx.doi.org/10.1111/jnc.14052] [PMID: 28791706]
[16]
Motter JN, Pelton GH, D’Antonio K, et al. Clinical and radiological characteristics of early versus late mild cognitive impairment in patients with comorbid depressive disorder. Int J Geriatr Psychiatry 2018; 33(12): 1604-12.
[http://dx.doi.org/10.1002/gps.4955] [PMID: 30035339]
[17]
Muñoz MD, de la Fuente N, Sánchez-Capelo A. TGF-β/Smad3 signalling modulates GABA neurotransmission: Implications in Parkinson’s disease. Int J Mol Sci 2020; 21(2): 590.
[http://dx.doi.org/10.3390/ijms21020590] [PMID: 31963327]
[18]
Jacobson L, Sapolsky R. The role of the hippocampus in feedback regulation of the hypothalamic-pituitary-adrenocortical axis. Endocr Rev 1991; 12(2): 118-34.
[http://dx.doi.org/10.1210/edrv-12-2-118] [PMID: 2070776]
[19]
Myers MG Jr, Olson DP. Central nervous system control of metabolism. Nature 2012; 491(7424): 357-63.
[http://dx.doi.org/10.1038/nature11705] [PMID: 23151578]
[20]
Ames A III. CNS energy metabolism as related to function. Brain Res Brain Res Rev 2000; 34(1-2): 42-68.
[http://dx.doi.org/10.1016/S0165-0173(00)00038-2] [PMID: 11086186]
[21]
Choeiri C, Staines W, Miki T, Seino S, Messier C. Glucose transporter plasticity during memory processing. Neuroscience 2005; 130(3): 591-600.
[http://dx.doi.org/10.1016/j.neuroscience.2004.09.011] [PMID: 15590143]
[22]
Traynelis SF, Wollmuth LP, McBain CJ, et al. Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev 2010; 62(3): 405-96.
[http://dx.doi.org/10.1124/pr.109.002451] [PMID: 20716669]
[23]
Nicoletti F, Bockaert J, Collingridge GL, et al. Metabotropic glutamate receptors: from the workbench to the bedside. Neuropharmacology 2011; 60(7-8): 1017-41.
[http://dx.doi.org/10.1016/j.neuropharm.2010.10.022] [PMID: 21036182]
[24]
Chaudhry FA, Reimer RJ, Edwards RH. The glutamine commute: take the N line and transfer to the A. J Cell Biol 2002; 157(3): 349-55.
[http://dx.doi.org/10.1083/jcb.200201070] [PMID: 11980913]
[25]
Schousboe A, Bak LK, Waagepetersen HS. Astrocytic control of biosynthesis and turnover of the neurotransmitters glutamate and GABA. Front Endocrinol (Lausanne) 2013; 4: 102.
[http://dx.doi.org/10.3389/fendo.2013.00102] [PMID: 23966981]
[26]
Li Z, Langhans SA. Transcriptional regulators of Na,K-ATPase subunits. Front Cell Dev Biol 2015; 3: 66.
[http://dx.doi.org/10.3389/fcell.2015.00066] [PMID: 26579519]
[27]
Pivovarov AS, Calahorro F, Walker RJ. Na+/K+-pump and neurotransmitter membrane receptors. Invert Neurosci 2018; 19(1): 1.
[http://dx.doi.org/10.1007/s10158-018-0221-7] [PMID: 30488358]
[28]
Attwell D, Laughlin SB. An energy budget for signaling in the grey matter of the brain. J Cereb Blood Flow Metab 2001; 21(10): 1133-45.
[http://dx.doi.org/10.1097/00004647-200110000-00001] [PMID: 11598490]
[29]
Vizi ES, Fekete A, Karoly R, Mike A. Non-synaptic receptors and transporters involved in brain functions and targets of drug treatment. Br J Pharmacol 2010; 160(4): 785-809.
[http://dx.doi.org/10.1111/j.1476-5381.2009.00624.x] [PMID: 20136842]
[30]
Weidemann H. Na/K-ATPase, endogenous digitalis like compounds and cancer development a hypothesis. Front Biosci 2005; 10: 2165-76.
[http://dx.doi.org/10.2741/1688] [PMID: 15970485]
[31]
Gritz SM, Radcliffe RA. Genetic effects of ATP1A2 in familial hemiplegic migraine type II and animal models. Hum Genomics 2013; 7(1): 8.
[http://dx.doi.org/10.1186/1479-7364-7-8] [PMID: 23561701]
[32]
Heinzen EL, Arzimanoglou A, Brashear A, et al. ATP1A3 Working Group. Distinct neurological disorders with ATP1A3 mutations. Lancet Neurol 2014; 13(5): 503-14.
[http://dx.doi.org/10.1016/S1474-4422(14)70011-0] [PMID: 24739246]
[33]
Erukainure OL, Hafizur RM, Kabir N, et al. Suppressive effects of clerodendrum volubile P beauv.[Labiatae] methanolic extract and its fractions on type 2 diabetes and its complications. Front Pharmacol 2018; 9: 8.
[http://dx.doi.org/10.3389/fphar.2018.00008] [PMID: 29449808]
[34]
Asogwa E, Otuonye A, Mokwunye F, Oluyole K, Ndubuaku T, Uwagboe E. Kolanut production, processing and marketing in the South-eastern states of Nigeria. Afr J Plant Sci 2011; 5: 547-51.
[35]
Dorathy IU, Okere SO, Daniel EE, Mubarak LL. Phytochemical constitutents and antidiabetic property of Cola nitida seeds on alloxan-induced diabetes mellitus in rats. Br J Pharm Res 2014; 4: 2631-41.
[http://dx.doi.org/10.9734/BJPR/2014/13071]
[36]
Oboh G, Ademosun AO, Ogunsuyi OB, Oyedola ET, Olasehinde TA, Oyeleye SI. In vitro anticholinesterase, antimonoamine oxidase and antioxidant properties of alkaloid extracts from kola nuts (Cola acuminata and Cola nitida). J Complement Integr Med 2018; 16(1)
[http://dx.doi.org/10.1515/jcim-2016-0155] [PMID: 30020887]
[37]
Imam-Fulani AO, Sanusi KO, Owoyele BV. Effects of acetone extract of Cola nitida on brain sodium-potassium adenosine triphosphatase activity and spatial memory in healthy and streptozotocin-induced diabetic female Wistar rats. J Basic Clin Physiol Pharmacol 2018; 29(4): 411-6.
[http://dx.doi.org/10.1515/jbcpp-2016-0019] [PMID: 29634481]
[38]
Farombi EO, Møller P, Dragsted LO. Ex-vivo and in vitro protective effects of kolaviron against oxygen-derived radical-induced DNA damage and oxidative stress in human lymphocytes and rat liver cells. Cell Biol Toxicol 2004; 20(2): 71-82.
[http://dx.doi.org/10.1023/B:CBTO.0000027916.61347.bc] [PMID: 15242183]
[39]
Adaramoye OA. Protective effect of kolaviron, a biflavonoid from Garcinia kola seeds, in brain of Wistar albino rats exposed to gamma-radiation. Biol Pharm Bull 2010; 33(2): 260-6.
[http://dx.doi.org/10.1248/bpb.33.260] [PMID: 20118550]
[40]
Igado OO, Olopade JO, Adesida A, Aina OO, Farombi EO. Morphological and biochemical investigation into the possible neuroprotective effects of kolaviron (Garcinia kola bioflavonoid) on the brains of rats exposed to vanadium. Drug Chem Toxicol 2012; 35(4): 371-80.
[http://dx.doi.org/10.3109/01480545.2011.630005] [PMID: 22288905]
[41]
Moneim A, Sulieman E. Garcinia kola (Bitter kola): Chemical composition. Wild fruits: composition, nutritional value and products) 2019; 285-99.
[42]
Umoren EB, Osim EE, Udoh PB. The comparative effects of chronic consumption of kola nut (Cola nitida) and caffeine diets on locomotor behaviour and body weights in mice. Nig J Physiol Sci 2009; 24(1)
[43]
Adeosun OI, Olaniyi KS, Amusa OA, Jimoh GZ, Oniyide AA. Methanolic extract of Cola nitida elicits dose-dependent diuretic, natriuretic and kaliuretic activities without causing electrolyte impairment, hepatotoxicity and nephrotoxicity in rats. Int J Physiol Pathophysiol Pharmacol 2017; 9(6): 231-9.
[PMID: 29348800]
[44]
Ikegwuonu FI, Aire TA, Ogwuegbu SO. Effects of kola-nut extract administration on the liver, kidney, brain, testis and some serum constituents of the rat. J Appl Toxicol 1981; 1(6): 292-4.
[http://dx.doi.org/10.1002/jat.2550010603] [PMID: 6193164]
[45]
Omotoso GO, Olajide OJ, Gbadamosi IT, et al. Cuprizone toxicity and Garcinia kola biflavonoid complex activity on hippocampal morphology and neurobehaviour. Heliyon 2019; 5(7): e02102.
[http://dx.doi.org/10.1016/j.heliyon.2019.e02102] [PMID: 31367687]
[46]
Ajayi SA. The effects of kolaviron (Methanolic extract of Garcinia kola seeds) on the histoarchitectural studies of the hypothalamo-pituitary-gonadal axis in female wistar rats. J Med Sci 2013; 13: 773-8.
[http://dx.doi.org/10.3923/jms.2013.773.778]
[47]
Lee YS, Silva AJ. The molecular and cellular biology of enhanced cognition. Nat Rev Neurosci 2009; 10(2): 126-40.
[http://dx.doi.org/10.1038/nrn2572] [PMID: 19153576]
[48]
McEntee WJ, Crook TH. Glutamate: its role in learning, memory, and the aging brain. Psychopharmacology (Berl) 1993; 111(4): 391-401.
[http://dx.doi.org/10.1007/BF02253527] [PMID: 7870979]
[49]
Ozawa S, Kamiya H, Tsuzuki K. Glutamate receptors in the mammalian central nervous system. Prog Neurobiol 1998; 54(5): 581-618.
[http://dx.doi.org/10.1016/S0301-0082(97)00085-3] [PMID: 9550192]
[50]
Sanz-Clemente A, Nicoll RA, Roche KW. Diversity in NMDA receptor composition: many regulators, many consequences. Neuroscientist 2013; 19(1): 62-75.
[http://dx.doi.org/10.1177/1073858411435129] [PMID: 22343826]
[51]
Liu T, Kong D, Shah BP, et al. Fasting activation of AgRP neurons requires NMDA receptors and involves spinogenesis and increased excitatory tone. Neuron 2012; 73(3): 511-22.
[http://dx.doi.org/10.1016/j.neuron.2011.11.027] [PMID: 22325203]
[52]
Hardingham GE, Fukunaga Y, Bading H. Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways. Nat Neurosci 2002; 5(5): 405-14.
[http://dx.doi.org/10.1038/nn835] [PMID: 11953750]
[53]
Xu J, Kurup P, Zhang Y, et al. Extrasynaptic NMDA receptors couple preferentially to excitotoxicity via calpain-mediated cleavage of STEP. J Neurosci 2009; 29(29): 9330-43.
[http://dx.doi.org/10.1523/JNEUROSCI.2212-09.2009] [PMID: 19625523]
[54]
Kanner BI. Structure and function of sodium-coupled GABA and glutamate transporters. J Membr Biol 2006; 213(2): 89-100.
[http://dx.doi.org/10.1007/s00232-006-0877-5] [PMID: 17417704]
[55]
Zhang LN, Sun YJ, Wang LX, Gao ZB. Glutamate transporters/Na+, K+-ATPase involving in the neuroprotective effect as a potential regulatory target of glutamate uptake. Mol Neurobiol 2016; 53(2): 1124-31.
[http://dx.doi.org/10.1007/s12035-014-9071-4] [PMID: 25586061]
[56]
Erukainure OL, Ijomone OM, Oyebode OA, Chukwuma CI, Aschner M, Islam MS. Hyperglycemia-induced oxidative brain injury: Therapeutic effects of Cola nitida infusion against redox imbalance, cerebellar neuronal insults, and upregulated Nrf2 expression in type 2 diabetic rats. Food Chem Toxicol 2019; 127: 206-17.
[http://dx.doi.org/10.1016/j.fct.2019.03.044] [PMID: 30914353]
[57]
Lu YF, Kandel ER, Hawkins RD. Nitric oxide signaling contributes to late-phase LTP and CREB phosphorylation in the hippocampus. J Neurosci 1999; 19(23): 10250-61.
[http://dx.doi.org/10.1523/JNEUROSCI.19-23-10250.1999] [PMID: 10575022]
[58]
Lorca RA, Rozas C, Loyola S, et al. Zinc enhances long-term potentiation through P2X receptor modulation in the hippocampal CA1 region. Eur J Neurosci 2011; 33(7): 1175-85.
[http://dx.doi.org/10.1111/j.1460-9568.2010.07589.x] [PMID: 21324005]
[59]
Codocedo JF, Godoy JA, Poblete MI, Inestrosa NC, Huidobro-Toro JP. ATP induces NO production in hippocampal neurons by P2X(7) receptor activation independent of glutamate signaling. PLoS One 2013; 8(3): e57626.
[http://dx.doi.org/10.1371/journal.pone.0057626] [PMID: 23472093]
[60]
Weitzdoerfer R, Hoeger H, Engidawork E, et al. Neuronal nitric oxide synthase knock-out mice show impaired cognitive performance. Nitric Oxide 2004; 10(3): 130-40.
[http://dx.doi.org/10.1016/j.niox.2004.03.007] [PMID: 15158692]
[61]
Zoubovsky SP, Pogorelov VM, Taniguchi Y, et al. Working memory deficits in neuronal nitric oxide synthase knockout mice: potential impairments in prefrontal cortex mediated cognitive function. Biochem Biophys Res Commun 2011; 408(4): 707-12.
[http://dx.doi.org/10.1016/j.bbrc.2011.04.097] [PMID: 21539806]
[62]
Hulbert AJ, Pamplona R, Buffenstein R, Buttemer WA. Life and death: metabolic rate, membrane composition, and life span of animals. Physiol Rev 2007; 87(4): 1175-213.
[http://dx.doi.org/10.1152/physrev.00047.2006] [PMID: 17928583]
[63]
Patel M. Targeting oxidative stress in central nervous system disorders. Trends Pharmacol Sci 2016; 37(9): 768-78.
[http://dx.doi.org/10.1016/j.tips.2016.06.007] [PMID: 27491897]
[64]
Salim S. Oxidative stress and the central nervous system. J Pharmacol Exp Ther 2017; 360(1): 201-5.
[http://dx.doi.org/10.1124/jpet.116.237503] [PMID: 27754930]
[65]
Siems WG, Hapner SJ, van Kuijk FJ. 4-hydroxynonenal inhibits Na(+)-K(+)-ATPase. Free Radic Biol Med 1996; 20(2): 215-23.
[http://dx.doi.org/10.1016/0891-5849(95)02041-1] [PMID: 8746442]
[66]
Butterfield DA, Lauderback CM. Lipid peroxidation and protein oxidation in Alzheimer’s disease brain: potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress. Free Radic Biol Med 2002; 32(11): 1050-60.
[http://dx.doi.org/10.1016/S0891-5849(02)00794-3] [PMID: 12031889]
[67]
Kangralkar VA, Patil SD, Bandivadekar RM. Oxidative stress and diabetes: a review. Int J Pharm 2010; 1(1): 38-45.

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