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CNS & Neurological Disorders - Drug Targets

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ISSN (Online): 1996-3181

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Research Article

Stingless Bee Honey Reduces Anxiety and Improves Memory of the Metabolic Disease-induced Rats

Author(s): Nurul ‘Ain Arshad, Teoh Seong Lin and Mohamad Fairuz Yahaya*

Volume 19, Issue 2, 2020

Page: [115 - 126] Pages: 12

DOI: 10.2174/1871527319666200117105133

Price: $65

Abstract

Background: Scientific studies support the evidence of the involvement of Metabolic Syndrome (MetS) in the progression of neurodegenerative diseases through oxidative stress. Consumption of antioxidant compounds was found to be beneficial for brain-health as it reduced the brain oxidative stress level and improved cognitive performance in animals. Stingless bee honey or locally known as Kelulut Honey (KH) has high phenolic content and is widely used as a food supplement.

Objectives: In this study, we aimed to investigate the effects of KH on the brain of MetS-induced rats.

Methods: Forty male Wistar rats were divided into 5 groups; 8 weeks (C8) and 16 weeks control groups (C16), groups that received High-Carbohydrate High Fructose (HCHF) diet for 8 weeks (MS8) and 16 weeks (MS16), and a group that received HCHF for 16 weeks with KH supplemented for the last 35 days (KH).

Results: Serum fasting blood glucose decreased in the KH group compared to the MS16 group. HDL levels were significantly decreased in MetS groups compared to control groups. Open field experiments showed that KH group exhibits less anxious behavior compared to the MetS group. Probe trial of Morris water maze demonstrated significant memory retention of KH group compared to the MS16 group. Nissl staining showed a significant decrease in the pyramidal hippocampal cells in the MS16 compared to the KH group.

Conclusion: KH has the ability to normalise blood glucose and reduce serum triglyceride and LDL levels in MetS rats, while behavior studies complement its effect on anxiety and memory. This shows a promising role of KH in attenuating neurodegenerative diseases through the antioxidant activity of its polyphenolic content.

Keywords: Kelulut honey, metabolic syndrome, brain, behavior, phenolic content, neurological function.

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Graphical Abstract

[1]
Saklayen MG. The global epidemic of the metabolic syndrome. Curr Hypertens Rep 2018; 20(2): 12.
[http://dx.doi.org/10.1007/s11906-018-0812-z] [PMID: 29480368]
[2]
Van Dyken P, Lacoste B, Talbot S, Menard C. Impact of metabolic syndrome on neuroinflammation and the blood-brain barrier. Front Neurosci 2018; 12: 930.
[http://dx.doi.org/10.3389/fnins.2018.00930] [PMID: 30618559]
[3]
Dinel A-L, André C, Aubert A, Ferreira G, Layé S, Castanon N. Cognitive and emotional alterations are related to hippocampal inflammation in a mouse model of metabolic syndrome. PLoS One 2011; 6(9)e24325
[http://dx.doi.org/10.1371/journal.pone.0024325] [PMID: 21949705]
[4]
Frisardi V, Solfrizzi V, Seripa D, et al. Metabolic-cognitive syndrome: a cross-talk between metabolic syndrome and Alzheimer’s disease. Ageing Res Rev 2010; 9(4): 399-417.
[http://dx.doi.org/10.1016/j.arr.2010.04.007] [PMID: 20444434]
[5]
Gómez-Caravaca AM, Gómez-Romero M, Arráez-Román D, Segura-Carretero A, Fernández-Gutiérrez A. Advances in the analysis of phenolic compounds in products derived from bees. J Pharm Biomed Anal 2006; 41(4): 1220-34.
[http://dx.doi.org/10.1016/j.jpba.2006.03.002] [PMID: 16621403]
[6]
White JW Honey. In: chichester CO, Ed Advances in Food Research. London: Academic Press 1978; pp. 287-374.
[7]
Gheldof N, Engeseth NJ. Antioxidant capacity of honeys from various floral sources based on the determination of oxygen radical absorbance capacity and inhibition of in vitro lipoprotein oxidation in human serum samples. J Agric Food Chem 2002; 50(10): 3050-5.
[http://dx.doi.org/10.1021/jf0114637] [PMID: 11982440]
[8]
Ferreres F, García-Viguera C, Tomás-Lorente F, Tomás-Barberán FA. Hesperetin: a marker of the floral origin of citrus honey. J Sci Food Agric 1993; 61: 121-3.
[http://dx.doi.org/10.1002/jsfa.2740610119]
[9]
Viuda-Martos M, Ruiz-Navajas Y, Fernández-López J, Pérez-Alvarez JA. Functional properties of honey, propolis, and royal jelly. J Food Sci 2008; 73(9): R117-24.
[http://dx.doi.org/10.1111/j.1750-3841.2008.00966.x] [PMID: 19021816]
[10]
Inoue K, Murayama S, Seshimo F, Takeba K, Yoshimura Y, Nakazawa H. Identification of phenolic compound in manuka honey as specific superoxide anion radical scavenger using Electron Spin Resonance (ESR) and liquid chromatography with coulometric array detection. J Sci Food Agric 2005; 85: 872-8.
[http://dx.doi.org/10.1002/jsfa.1952]
[11]
Allen KL, Molan PC, Reid GM. A survey of the antibacterial activity of some New Zealand honeys. J Pharm Pharmacol 1991; 43(12): 817-22.
[http://dx.doi.org/10.1111/j.2042-7158.1991.tb03186.x] [PMID: 1687577]
[12]
Mathews KA, Binnington AG. Wound management using honey. Compendium 2002; 24: 53-60.
[13]
Mossel DA. Honey for necrotic breast ulcers. Lancet 1980; 2(8203): 1091.
[http://dx.doi.org/10.1016/S0140-6736(80)92322-3] [PMID: 6107720]
[14]
Kek SP, Chin NL, Yusof YA, Tan SW, Chua LS. Total phenolic contents and colour intensity of Malaysian honeys from the Apis spp. and Trigona spp. bees. Agric Agric Sci Procedia 2014; 2: 150-5.
[http://dx.doi.org/10.1016/j.aaspro.2014.11.022]
[15]
Ramli NZ, Chin K-Y, Zarkasi KA, Ahmad F. The beneficial effects of stingless bee honey from Heterotrigona itama against metabolic changes in rats fed with high-carbohydrate and high-fat diet. Int J Environ Res Public Health 2019; 16(24)E4987
[http://dx.doi.org/10.3390/ijerph16244987] [PMID: 31817937]
[16]
Aziz MSA, Giribabu N, Rao PV, Salleh N. Pancreatoprotective effects of Geniotrigona thoracica stingless bee honey in streptozotocin-nicotinamide-induced male diabetic rats. Biomed Pharmacother 2017; 89: 135-45.
[http://dx.doi.org/10.1016/j.biopha.2017.02.026] [PMID: 28222394]
[17]
Abdulmajeed WI, Sulieman HB, Zubayr MO, et al. Honey prevents neurobehavioural deficit and oxidative stress induced by lead acetate exposure in male Wistar rats- a preliminary study. Metab Brain Dis 2016; 31(1): 37-44.
[http://dx.doi.org/10.1007/s11011-015-9733-6] [PMID: 26435406]
[18]
Wong SK, Chin KY, Suhaimi FH, Ahmad F, Ima-Nirwana S. The effects of a modified high-carbohydrate high-fat diet on metabolic syndrome parameters in male rats. Exp Clin Endocrinol Diabetes 2018; 126(4): 205-12.
[http://dx.doi.org/10.1055/s-0043-119352] [PMID: 29117620]
[19]
Kumar MV, Sambaiah K, Lokesh BR. Effect of dietary ghee--the anhydrous milk fat, on blood and liver lipids in rats. J Nutr Biochem 1999; 10(2): 96-104.
[http://dx.doi.org/10.1016/S0955-2863(98)00088-6] [PMID: 15539276]
[20]
Sharma HB, Vyas S, Kumar J, Manna S. Beneficial effect of ghee consumption over mustard oil on lipid profile: A study in North Indian adult population. J Complement Integr Med 2018; 15(3): 1-7.
[http://dx.doi.org/10.1515/jcim-2017-0101] [PMID: 29369816]
[21]
Mumme K, Stonehouse W. Effects of medium-chain triglycerides on weight loss and body composition: a meta-analysis of randomized controlled trials. J Acad Nutr Diet 2015; 115(2): 249-63.
[http://dx.doi.org/10.1016/j.jand.2014.10.022] [PMID: 25636220]
[22]
House RL, Cassady JP, Eisen EJ, McIntosh MK, Odle J. Conjugated linoleic acid evokes de-lipidation through the regulation of genes controlling lipid metabolism in adipose and liver tissue. Obes Rev 2005; 6(3): 247-58.
[http://dx.doi.org/10.1111/j.1467-789X.2005.00198.x] [PMID: 16045640]
[23]
Kennedy A, Martinez K, Schmidt S, Mandrup S, LaPoint K, McIntosh M. Antiobesity mechanisms of action of conjugated linoleic acid. J Nutr Biochem 2010; 21(3): 171-9.
[http://dx.doi.org/10.1016/j.jnutbio.2009.08.003] [PMID: 19954947]
[24]
Kesari AN, Gupta RK, Singh SK, Diwakar S, Watal G. Hypoglycemic and antihyperglycemic activity of Aegle marmelos seed extract in normal and diabetic rats. J Ethnopharmacol 2006; 107(3): 374-9.
[http://dx.doi.org/10.1016/j.jep.2006.03.042] [PMID: 16781099]
[25]
Kitagawa A, Ohta Y, Ohashi K. Melatonin improves metabolic syndrome induced by high fructose intake in rats. J Pineal Res 2012; 52(4): 403-13.
[http://dx.doi.org/10.1111/j.1600-079X.2011.00955.x] [PMID: 22220562]
[26]
Ross AP, Bartness TJ, Mielke JG, Parent MB. A high fructose diet impairs spatial memory in male rats. Neurobiol Learn Mem 2009; 92(3): 410-6.
[http://dx.doi.org/10.1016/j.nlm.2009.05.007] [PMID: 19500683]
[27]
Xia S-F, Xie Z-X, Qiao Y, et al. Differential effects of quercetin on hippocampus-dependent learning and memory in mice fed with different diets related with oxidative stress. Physiol Behav 2015; 138: 325-31.
[http://dx.doi.org/10.1016/j.physbeh.2014.09.008] [PMID: 25447470]
[28]
Bogdanov S. Honey as nutrient and functional food: a review. Bee Prod Sci 2015; pp. 1-47.
[29]
Tomaand́s-Barberaand́n FA, Martos I, Ferreres F, Radovic BS, Anklam E. HPLC flavonoid profiles as markers for the botanical origin of European unifloral honeys. J Sci Food Agric 2001; 48: 4744-8.
[30]
Al-Waili NS. Effects of daily consumption of honey solution on hematological indices and blood levels of minerals and enzymes in normal individuals. J Med Food 2003; 6(2): 135-40.
[http://dx.doi.org/10.1089/109662003322233549] [PMID: 12935325]
[31]
Akhtar MS, Khan MS. Glycaemic responses to three different honeys given to normal and alloxan-diabetic rabbits. J Pak Med Assoc 1989; 39(4): 107-13.
[PMID: 2501525]
[32]
Erejuwa OO, Sulaiman SA, Wahab MS, Sirajudeen KNS, Salleh MSMD, Gurtu S. Antioxidant protection of Malaysian tualang honey in pancreas of normal and streptozotocin-induced diabetic rats. Ann Endocrinol (Paris) 2010; 71(4): 291-6.
[http://dx.doi.org/10.1016/j.ando.2010.03.003] [PMID: 20398890]
[33]
Fasanmade AA, Alabi OT. Differential effect of honey on selected variables in alloxan-induced and fructose-induced diabetic rats. Afr J Biomed Res 2008; 11: 191-6.
[34]
Basu A, Lyons TJ. Strawberries, blueberries, and cranberries in the metabolic syndrome: clinical perspectives. J Agric Food Chem 2012; 60(23): 5687-92.
[http://dx.doi.org/10.1021/jf203488k] [PMID: 22082311]
[35]
Egert S, Boesch-Saadatmandi C, Wolffram S, Rimbach G, Müller MJ. Serum lipid and blood pressure responses to quercetin vary in overweight patients by apolipoprotein E genotype. J Nutr 2010; 140(2): 278-84.
[http://dx.doi.org/10.3945/jn.109.117655] [PMID: 20032478]
[36]
Rivera L, Morón R, Sánchez M, Zarzuelo A, Galisteo M. Quercetin ameliorates metabolic syndrome and improves the inflammatory status in obese Zucker rats. Obesity (Silver Spring) 2008; 16(9): 2081-7.
[http://dx.doi.org/10.1038/oby.2008.315] [PMID: 18551111]
[37]
Huang HC, Lin JK. Pu-erh tea, green tea, and black tea suppresses hyperlipidemia, hyperleptinemia and fatty acid synthase through activating AMPK in rats fed a high-fructose diet. Food Funct 2012; 3(2): 170-7.
[http://dx.doi.org/10.1039/C1FO10157A] [PMID: 22127373]
[38]
Liu CY, Huang CJ, Huang LH, Chen IJ, Chiu JP, Hsu CH. Effects of green tea extract on insulin resistance and glucagon-like peptide 1 in patients with type 2 diabetes and lipid abnormalities: a randomized, double-blinded, and placebo-controlled trial. PLoS One 2014; 9(3)e91163
[http://dx.doi.org/10.1371/journal.pone.0091163] [PMID: 24614112]
[39]
Rahigude A, Bhutada P, Kaulaskar S, Aswar M, Otari K. Participation of antioxidant and cholinergic system in protective effect of naringenin against type-2 diabetes-induced memory dysfunction in rats. Neuroscience 2012; 226: 62-72.
[http://dx.doi.org/10.1016/j.neuroscience.2012.09.026] [PMID: 22999973]
[40]
Nagao T, Meguro S, Hase T, et al. A catechin-rich beverage improves obesity and blood glucose control in patients with type 2 diabetes. Obesity (Silver Spring) 2009; 17(2): 310-7.
[http://dx.doi.org/10.1038/oby.2008.505] [PMID: 19008868]
[41]
Yokozawa T, Kim HJ, Cho EJ. Gravinol ameliorates high-fructose-induced metabolic syndrome through regulation of lipid metabolism and proinflammatory state in rats. J Agric Food Chem 2008; 56(13): 5026-32.
[http://dx.doi.org/10.1021/jf800213f] [PMID: 18540612]
[42]
Chepulis L, Starkey N. The long-term effects of feeding honey compared with sucrose and a sugar-free diet on weight gain, lipid profiles, and DEXA measurements in rats. J Food Sci 2008; 73(1): H1-7.
[http://dx.doi.org/10.1111/j.1750-3841.2007.00592.x] [PMID: 18211352]
[43]
Oyekunle OA, Akanmu MA, Ogundeji TP. Evaluation of anxiolytic and novelty induced behaviours following bee-honey consumption in rats. J Neurosci Behav Health 2010; 2: 38-43.
[44]
Biluca FC, de Gois JS, Schulz M, et al. Phenolic compounds, antioxidant capacity and bioaccessibility of minerals of stingless bee honey (Meliponinae). J Food Compos Anal 2017; 63: 89-97.
[http://dx.doi.org/10.1016/j.jfca.2017.07.039]
[45]
Makhathini KB, Mabandla MV, Daniels WMU. Rosmarinic acid reverses the deleterious effects of repetitive stress and tat protein. Behav Brain Res 2018; 353: 203-9.
[http://dx.doi.org/10.1016/j.bbr.2018.07.010] [PMID: 30029998]
[46]
de Souza TB, Farias DM, Coletti RF, et al. Systemic Administration of antipsychotic asenapine pre or postnatal does not induce anxiety-like behaviors in mice. CNS Neurol Disord Drug Targets 2018; 16(10): 1127-33.
[http://dx.doi.org/10.2174/1871527317666171213162403] [PMID: 29237385]
[47]
Akanmu MA, Olowookere TA, Atunwa SA, et al. Neuropharmacological effects of Nigerian honey in mice. Afr J Tradit Complement Altern Med 2011; 8(3): 230-49.
[http://dx.doi.org/10.4314/ajtcam.v8i3.65285] [PMID: 22468002]
[48]
Pérez E, Rodríguez-Malaver AJ, Vit P. Antioxidant capacity of Venezuelan honey in wistar rat homogenates. J Med Food 2006; 9(4): 510-6.
[http://dx.doi.org/10.1089/jmf.2006.9.510] [PMID: 17201638]
[49]
Gill-Sharma MK, D’Souza S, Parte P, et al. Effect of oral tamoxifen on semen characteristics and serum hormone profile in male bonnet monkeys. Contraception 2003; 67(5): 409-13.
[http://dx.doi.org/10.1016/S0010-7824(03)00018-0] [PMID: 12742566]
[50]
Al-Himyari FA. The use of honey as a natural preventive therapy of cognitive decline and dementia in the middle east. Alzheimers Dement 2009; 5: 247.
[http://dx.doi.org/10.1016/j.jalz.2009.04.248]
[51]
Azman KF, Zakaria R, AbdAziz C, Othman Z, Al-Rahbi B. Tualang honey improves memory performance and decreases depressive-like behavior in rats exposed to loud noise stress. Noise Health 2015; 17(75): 83-9.
[http://dx.doi.org/10.4103/1463-1741.153388] [PMID: 25774610]
[52]
Al-Rahbi B, Zakaria R, Othman Z, Hassan A, Ahmad AH. Protective effects of Tualang honey against oxidative stress and anxiety-like behaviour in stressed ovariectomized rats. Int Sch Res Notices 2014; 2014521065
[http://dx.doi.org/10.1155/2014/521065] [PMID: 27379299]
[53]
Othman Z, Shafin N, Zakaria R, Hussain NHN, Mohammad WMZW. Improvement in immediate memory after 16 weeks of tualang honey (Agro Mas) supplement in healthy postmenopausal women. Menopause 2011; 18(11): 1219-24.
[http://dx.doi.org/10.1097/gme.0b013e31821e2044] [PMID: 21926932]
[54]
Othman Z, Zakaria R, Hussain NHN, et al. Potential role of honey in learning and memory. Med Sci (Basel) 2015; 3(2): 3-15.
[http://dx.doi.org/10.3390/medsci3020003] [PMID: 29083387]
[55]
Goldschmidt S, Burkert H. [Hydrolysis of the cholinergic substance and other choline esters of honey by cholinesterases, and their inhibition in honey]. Hoppe Seylers Z Physiol Chem 1955; 301(1-2): 78-89.
[http://dx.doi.org/10.1515/bchm2.1955.301.1-2.78] [PMID: 13294822]
[56]
Al-Rahbi B, Zakaria R, Othman Z, Hassan A, Mohd Ismail ZI, Muthuraju S. Tualang honey supplement improves memory performance and hippocampal morphology in stressed ovariectomized rats. Acta Histochem 2014; 116(1): 79-88.
[http://dx.doi.org/10.1016/j.acthis.2013.05.004] [PMID: 23810156]
[57]
Ghanbari A, Zibara K, Salari S, et al. Light-Emitting Diode (LED) therapy attenuates neurotoxicity of methanol-induced memory impairment and apoptosis in the hippocampus. CNS Neurol Disord Drug Targets 2018; 17(7): 528-38.
[http://dx.doi.org/10.2174/1871527317666180703111643] [PMID: 29968547]
[58]
Arshad N, Lin TS, Yahaya MF. Metabolic syndrome and its effect on the brain: possible mechanism. CNS Neurol Disord Drug Targets 2018; 17(8): 595-603.
[PMID: 30047340]
[59]
Anil Kumar S, Saif SA, Oothuman P, Mustafa MIA. Lipid peroxidation in chronic cerebral hypoperfusion-induced neurodegeneration in rats. Int Med J Malays 2011; 10: 3-6.
[60]
Ghavaminia R, Sohrabi D, Arianmanesh M, Alipour M, Anarkooli IJ. Insulin and natural honey changes hippocampal BCL-2 family gene expression, superoxide dismutase activity, and passive avoidance memory in streptozotocin-induced diabetic rats. Eur J Pharm Med Res 2016; 3: 145-53.
[61]
Esposito E, Rotilio D, Di Matteo V, Di Giulio C, Cacchio M, Algeri S. A review of specific dietary antioxidants and the effects on biochemical mechanisms related to neurodegenerative processes. Neurobiol Aging 2002; 23(5): 719-35.
[http://dx.doi.org/10.1016/S0197-4580(02)00078-7] [PMID: 12392777]
[62]
Lau FC, Shukitt-Hale B, Joseph JA. The beneficial effects of fruit polyphenols on brain aging. Neurobiol Aging 2005; 26(Suppl. 1): 128-32.
[http://dx.doi.org/10.1016/j.neurobiolaging.2005.08.007] [PMID: 16194581]
[63]
Rezai-Zadeh K, Ehrhart J, Bai Y, et al. Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression. J Neuroinflammation 2008; 5: 41.
[http://dx.doi.org/10.1186/1742-2094-5-41] [PMID: 18817573]
[64]
Li Y, Shi W, Li Y, et al. Neuroprotective effects of chlorogenic acid against apoptosis of PC12 cells induced by methylmercury. Environ Toxicol Pharmacol 2008; 26(1): 13-21.
[http://dx.doi.org/10.1016/j.etap.2007.12.008] [PMID: 21783882]
[65]
Yam-Puc A, Santana-Hernández AA, Yah-Nahuat PN, et al. Pentacyclic triterpenes and other constituents in propolis extract from Melipona beecheii collected in Yucatan, México. Rev Bras Farmacogn 2019; 29: 358-63.
[http://dx.doi.org/10.1016/j.bjp.2019.01.006]
[66]
Wang K, Sun W, Zhang L, et al. Oleanolic acid ameliorates Aβ25-35 injection-induced memory deficit in Alzheimer’s disease model rats by maintaining synaptic plasticity. CNS Neurol Disord Drug Targets 2018; 17(5): 389-99.
[http://dx.doi.org/10.2174/1871527317666180525113109] [PMID: 29793416]

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