Neuroprotective effects of Rosa damascena extract on learning and memory in a rat model of amyloid-β-induced Alzheimer`s disease

Authors

1 Department of Anatomical Sciences and Molecular Biology, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Physiology, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran

3 Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran

4 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

5 Department of Biology, Cells, Molecular Biology and Biochemistry Division, Faculty of Sciences, University of Isfahan, Isfahan, Iran

Abstract

Background: Alzheimer's disease (AD) is an age-related progressive neurodegenerative disease, which is characterized clinically by serious impairment in memory and cognition. Current medications only slow down the dementia progression and the present treatment one-drug one-target paradigm for anti-AD treatment appears to be clinically unsuccessful. Therefore, alternative therapeutic strategies are urgently needed. With respect to multifunctional and multitargeted characteristics of Rosa damascena via its effective flavonoids, we investigated the effects of R. damascena extract on behavioral functions in a rat model of amyloid-β (A-β)-induced Alzheimer's disease.
Materials and Methods: After preparation of the methanolic extract of the R. damascena, HPLC analysis and toxicity studies, median lethal dose (LD50) and dose levels were determined. For evaluation of baseline training behavioral performance, Morris water maze and passive avoidance tests were used. A-β was injected bilaterally into CA1 area of the hippocampus. Twenty-one days after injection of A-β, the first probe trial of the behavioral tests were used to confirm learning and memory impairment. To examine the potential effects of the extract on behavioral tasks, the second probe trials were performed after one month administration of R. damasena extract.
Results: Results showed that the R. damascena extract significantly improved the spatial and long-term memories in the extract- treated groups in a dose-dependent manner, as in the middle and high doses it had significant effect.
Conclusion: According to these results, we concluded that R. damascena can reverse behavioral deficits caused by A-β, and may provide a new potential option for prevention and treatment of the cognitive dysfunction in Alzheimer's disease.

Keywords

1.
Selkoe DJ. The molecular pathology of Alzheimer's disease. Neuron 1991;6:487.  Back to cited text no. 1
    
2.
Lee JK, Jin HK, Endo S, Schuchman EH, Carter JE, Bae JS. Intracerebral transplantation of bone marrow-derived mesenchymal stem cells reduces amyloid-beta deposition and rescues memory deficits in Alzheimer's disease mice by modulation of immune responses. Stem Cells 2010;28:329-43.  Back to cited text no. 2
    
3.
Selkoe DJ. Alzheimer's disease: Genes, proteins, and therapy. Physiol Rev 2001;81:741-66.  Back to cited text no. 3
    
4.
Rogers J, Webster S, Lue LF, Brachova L, Civin WH, Emmerling M, et al. Inflammation and Alzheimer's disease pathogenesis. Neurobiol Aging 1996;17:681-6.  Back to cited text no. 4
    
5.
Scheff SW, Price DA, Schmitt FA, DeKosky ST, Mufson EJ. Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment. Neurology 2007;68:1501-8.  Back to cited text no. 5
    
6.
Huang HC, Jiang ZF. Accumulated amyloid-beta peptide and hyperphosphorylated tau protein: Relationship and links in Alzheimer's disease. J Alzheimers Dis 2009;16:15-27.  Back to cited text no. 6
    
7.
Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics. Science 2002;297:353-6.  Back to cited text no. 7
    
8.
Querfurth HW, LaFerla FM. Alzheimer's disease. N Engl J Med 2010;362:329-44.  Back to cited text no. 8
    
9.
Salloway S, Ferris S, Kluger A, Goldman R, Griesing T, Kumar D, et al. Efficacy of donepezil in mild cognitive impairment: A randomized placebo-controlled trial. Neurology 2004;63:651-7.  Back to cited text no. 9
    
10.
Kim HG, Oh MS. Herbal medicines for the prevention and treatment of Alzheimer's disease. Curr Pharm Des 2012;18:57-75.  Back to cited text no. 10
    
11.
Kalim MD, Bhattacharyya D, Banerjee A, Chattopadhyay S. Oxidative DNA damage preventive activity and antioxidant potential of plants used in Unani system of medicine. BMC Complement Altern Med 2010;10:77.  Back to cited text no. 11
    
12.
Schiber A, Mihalev K, Berardini N, Mollov P, Carle R. Flavonol glycosides from distilled petals of Rosa damascena Mill. Z Naturforsch C 2005;60:379-84.  Back to cited text no. 12
    
13.
Ramezani R, Moghimi A, Rakhshandeh H, Ejtehadi H, Kheirabadi M. The effect of Rosa damascena essential oil on the amygdala electrical kindling seizures in rat. Pak J Biol Sci 2008;11:746-51.  Back to cited text no. 13
    
14.
Awale S, Tohda C, Tezuka Y, Miyazaki M, Kadota S. Protective Effects of Rosa damascena and its Active Constituent on A {beta}(25-35)-induced Neuritic Atrophy. Evid Based Complement Alternat Med 2011;2011:131042.  Back to cited text no. 14
    
15.
Hongratanaworakit T. Relaxing effect of rose oil on humans. Nat Prod Commun 2009;4:291-6.  Back to cited text no. 15
    
16.
Spencer JP. The impact of fruit flavonoids on memory and cognition. Br J Nutr 2010;104:S40-7.  Back to cited text no. 16
    
17.
Kumar N, Bhandari P, Singh B, Gupta AP, Kaul VK. Reversed phase-HPLC for rapid determination of polyphenols in flowers of rose species. J Sep Sci 2008;31:262-7.  Back to cited text no. 17
    
18.
Yu KH, Nation RL, Dooley MJ. Multiplicity of medication safety terms, definitions and functional meanings: When is enough enough? Qual Saf Health Care 2005;14:358-63.  Back to cited text no. 18
    
19.
Akhila J. Shetty, Deepa Shyamjith, Alwar M. C. Acute toxicity studies and determination of median lethal dose. Curr Sci 2007;93:917-20.  Back to cited text no. 19
    
20.
Poole AF, Leslie GB. A practical approach to toxicological investigations. Cambridge, England: Cambridge University Press;1989.  Back to cited text no. 20
    
21.
Javan M, Ahmadiani A, Semnanian S, Kamalinejad M. Antinociceptive effects of Trigonella foenum-graecum leaves extract. J Ethnopharmacol 1997;58:125-9.  Back to cited text no. 21
    
22.
Pant J, Deshpande SB. Acute toxicity of Bisphenol A in rats. Indian J Exp Biol 2012;50:425-9.  Back to cited text no. 22
    
23.
Jagetia G, Baliga M, Malagi K, Sethukumar Kamath M. The evaluation of the radioprotective effect of Triphala (an ayurvedic rejuvenating drug) in the mice exposed to g-radiation. Phytomedicine 2002;9:99-108.  Back to cited text no. 23
    
24.
Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates: Hard Cover Edition. United States: Academic press; 2007.  Back to cited text no. 24
    
25.
Morris RG, Garrud P, Rawlins JN, O'Keefe J. Place navigation impaired in rats with hippocampal lesions. Nature 1982;297:681-3.  Back to cited text no. 25
    
26.
de Quervain DJ, Roozendaal B, McGaugh JL. Stress and glucocorticoids impair retrieval of long-term spatial memory. Nature 1998;394:787-90.  Back to cited text no. 26
    
27.
Frick KM, Kim JJ, Baxter MG. Effects of complete immunotoxin lesions of the cholinergic basal forebrain on fear conditioning and spatial learning. Hippocampus 2004;14:244-54.  Back to cited text no. 27
    
28.
Venault P, Chapouthier G, de Carvalho LP, Simiand J, Morre M, Dodd RH, et al. Benzodiazepine impairs and beta-carboline enhances performance in learning and memory tasks. Nature 1986;321:864-6.  Back to cited text no. 28
    
29.
Mazzola C, Micale V, Drago F. Amnesia induced by beta-amyloid fragments is counteracted by cannabinoid CB1 receptor blockade. Eur J Pharmacol 2003;477:219-25.  Back to cited text no. 29
    
30.
Abdel-Aal RA, Assi AA, Kostandy BB. Rivastigmine reverses aluminum-induced behavioral changes in rats. Eur J Pharmacol 2011;659:169-76.  Back to cited text no. 30
    
31.
Scarpini E, Scheltens P, Feldman H. Treatment of Alzheimer's disease: Current status and new perspectives. Lancet Neurol 2003;2:539-47.  Back to cited text no. 31
    
32.
Cummings JL. Alzheimer's disease. N Engl J Med 2004;351:56-67.  Back to cited text no. 32
    
33.
Youdim MB, Buccafusco JJ. Multi-functional drugs for various CNS targets in the treatment of neurodegenerative disorders. Trends Pharmacol Sci 2005;26:27-35.  Back to cited text no. 33
    
34.
Pimplikar SW. Reassessing the amyloid cascade hypothesis of Alzheimer's disease. Int J Biochem Cell Biol 2009;41:1261-8.  Back to cited text no. 34
    
35.
Klafki HW, Staufenbiel M, Kornhuber J, Wiltfang J. Therapeutic approaches to Alzheimer's disease. Brain 2006;129:2840-55.  Back to cited text no. 35
    
36.
Manach C, Scalbert A, Morand C, Remesy C, Jimenez L. Polyphenols: Food sources and bioavailability. Am J Clin Nutr 2004;79:727-47.  Back to cited text no. 36
    
37.
Youdim KA, Joseph JA. A possible emerging role of phytochemicals in improving age-related neurological dysfunctions: A multiplicity of effects. Free Radic Biol Med 2001;30:583-94.  Back to cited text no. 37
    
38.
Raskin I, Ribnicky DM, Komarnytsky S, Ilic N, Poulev A, Borisjuk N, et al. Plants and human health in the twenty-first century. Trends Biotechnol 2002;20:522-31.  Back to cited text no. 38
    
39.
Kim DS, Kim JY, Han YS. Alzheimer's disease drug discovery from herbs: Neuroprotectivity from beta-amyloid (1-42) insult. J Altern Complement Med 2007;13:333-40.  Back to cited text no. 39
    
40.
Park SY, Kim DS. Discovery of natural products from Curcuma longa that protect cells from beta-amyloid insult: A drug discovery effort against Alzheimer's disease. J Nat Prod 2002;65:1227-31.  Back to cited text no. 40
    
41.
Jarrard LE. On the role of the hippocampus in learning and memory in the rat. Behav Neural Biol 1993;60:9-26.  Back to cited text no. 41
    
42.
Jhoo JH, Kim HC, Nabeshima T, Yamada K, Shin EJ, Jhoo WK, et al. Beta-amyloid (1-42)-induced learning and memory deficits in mice: Involvement of oxidative burdens in the hippocampus and cerebral cortex. Behav Brain Res 2004;155:185-96.  Back to cited text no. 42
    
43.
Yamada K, Takayanagi M, Kamei H, Nagai T, Dohniwa M, Kobayashi K, et al. Effects of memantine and donepezil on amyloid beta-induced memory impairment in a delayed-matching to position task in rats. Behav Brain Res 2005;162:191-9.  Back to cited text no. 43
    
44.
Joseph JA, Shukitt-Hale B, Denisova NA, Prior RL, Cao G, Martin A, et al. Long-term dietary strawberry, spinach, or vitamin E supplementation retards the onset of age-related neuronal signal-transduction and cognitive behavioral deficits. J Neurosci 1998;18:8047-55.  Back to cited text no. 44
    
45.
Joseph JA, Shukitt-Hale B, Denisova NA, Bielinski D, Martin A, McEwen JJ, et al. Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation. J Neurosci 1999;19:8114-21.  Back to cited text no. 45
    
46.
Casadesus G, Shukitt-Hale B, Stellwagen HM, Zhu X, Lee HG, Smith MA, et al. Modulation of hippocampal plasticity and cognitive behavior by short-term blueberry supplementation in aged rats. Nutr Neurosci 2004;7:309-16.  Back to cited text no. 46
    
47.
Goyarzu P, Malin DH, Lau FC, Taglialatela G, Moon WD, Jennings R, et al. Blueberry supplemented diet: Effects on object recognition memory and nuclear factor-kappa B levels in aged rats. Nutr Neurosci 2004;7:75-83.  Back to cited text no. 47
    
48.
Joseph JA, Shukitt-Hale B, Casadesus G. Reversing the deleterious effects of aging on neuronal communication and behavior: Beneficial properties of fruit polyphenolic compounds. Am J Clin Nutr 2005;81:313S-6.  Back to cited text no. 48
    
49.
Schroeter H, Heiss C, Balzer J, Kleinbongard P, Keen CL, Hollenberg NK, et al. (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proc Natl Acad Sci U S A 2006;103:1024-9.  Back to cited text no. 49
    
50.
Spencer JP. The interactions of flavonoids within neuronal signalling pathways. Genes Nutr 2007;2:257-73.  Back to cited text no. 50
    
51.
Spencer JP. The impact of flavonoids on memory: Physiological and molecular considerations. Chem Soc Rev 2009;38:1152-61.  Back to cited text no. 51
    
52.
Chen JC, Ho FM, Pei-Dawn Lee C, Chen CP, Jeng KC, Hsu HB, et al. Inhibition of iNOS gene expression by quercetin is mediated by the inhibition of IkappaB kinase, nuclear factor-kappa B and STAT1, and depends on heme oxygenase-1 induction in mouse BV-2 microglia. Eur J Pharmacol 2005;521:9-20.  Back to cited text no. 52
    
53.
Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 1996;20:933-56.  Back to cited text no. 53
    
54.
Rice-Evans CA, Miller NJ, Bolwell PG, Bramley PM, Pridham JB. The relative antioxidant activities of plant-derived polyphenolic flavonoids. Free Radic Res 1995;22:375-83.  Back to cited text no. 54
    
55.
Bors W, Heller W, Michel C, Saran M. Flavonoids as antioxidants: Determination of radical-scavenging efficiencies. Methods Enzymol 1990;186:343-55.  Back to cited text no. 55
    
56.
Flood JF, Landry DW, Jarvik ME. Cholinergic receptor interactions and their effects on long-term memory processing. Brain Res 1981;215:177-85.  Back to cited text no. 56
    
57.
Power AE, Vazdarjanova A, McGaugh JL. Muscarinic cholinergic influences in memory consolidation. Neurobiol Learn Mem 2003;80:178-93.  Back to cited text no. 57
    
58.
Ahmed T, Gilani AH. Inhibitory effect of curcuminoids on acetylcholinesterase activity and attenuation of scopolamine-induced amnesia may explain medicinal use of turmeric in Alzheimer's disease. Pharmacol Biochem Behav 2009;91:554-9.  Back to cited text no. 58
    
59.
Haass C. Take five-BACE and the gamma-secretase quartet conduct Alzheimer's amyloid beta-peptide generation. EMBO J 2004;23:483-8.  Back to cited text no. 59
    
60.
Guo T, Hobbs DW. Development of BACE1 inhibitors for Alzheimer's disease. Curr Med Chem 2006;13:1811-29.  Back to cited text no. 60
    
61.
Shimmyo Y, Kihara T, Akaike A, Niidome T, Sugimoto H. Multifunction of myricetin on A beta: Neuroprotection via a conformational change of A beta and reduction of A beta via the interference of secretases. J Neurosci Res 2008;86:368-77.  Back to cited text no. 61
    
62.
McLaurin J, Kierstead ME, Brown ME, Hawkes CA, Lambermon MH, Phinney AL, et al. Cyclohexanehexol inhibitors of Abeta aggregation prevent and reverse Alzheimer phenotype in a mouse model. Nat Med 2006;12:801-8.  Back to cited text no. 62
    
63.
Mattson MP. Pathways towards and away from Alzheimer's disease. Nature 2004;430:631-9.  Back to cited text no. 63
    
64.
Shimmyo Y, Kihara T, Akaike A, Niidome T, Sugimoto H. Flavonols and flavones as BACE-1 inhibitors: Structure-activity relationship in cell-free, cell-based and in silico studies reveal novel pharmacophore features. Biochim Biophys Acta 2008;1780:819-25.  Back to cited text no. 64