BACKGROUND/OBJECTIVES: Alzheimer's disease (AD) is characterized by deficits in memory and cognitive functions. The accumulation of amyloid beta peptide ($A{\beta}$) and oxidative stress in the brain are the most common causes of AD. MATERIALS/METHODS: Caffeic acid (CA) is an active pheno...
BACKGROUND/OBJECTIVES: Alzheimer's disease (AD) is characterized by deficits in memory and cognitive functions. The accumulation of amyloid beta peptide ($A{\beta}$) and oxidative stress in the brain are the most common causes of AD. MATERIALS/METHODS: Caffeic acid (CA) is an active phenolic compound that has a variety of pharmacological actions. We studied the protective abilities of CA in an $A{\beta}_{25-35}$-injected AD mouse model. CA was administered at an oral dose of 10 or 50 mg/kg/day for 2 weeks. Behavioral tests including T-maze, object recognition, and Morris water maze were carried out to assess cognitive abilities. In addition, lipid peroxidation and nitric oxide (NO) production in the brain were measured to investigate the protective effect of CA in oxidative stress. RESULTS: In the T-maze and object recognition tests, novel route awareness and novel object recognition were improved by oral administration of CA compared with the $A{\beta}_{25-35}$-injected control group. These results indicate that administration of CA improved spatial cognitive and memory functions. The Morris water maze test showed that memory function was enhanced by administration of CA. In addition, CA inhibited lipid peroxidation and NO formation in the liver, kidney, and brain compared with the $A{\beta}_{25-35}$-injected control group. In particular, CA 50 mg/kg/day showed the stronger protective effect from cognitive impairment than CA 10 mg/kg/day. CONCLUSIONS: The present results suggest that CA improves $A{\beta}_{25-35}$-induced memory deficits and cognitive impairment through inhibition of lipid peroxidation and NO production.
BACKGROUND/OBJECTIVES: Alzheimer's disease (AD) is characterized by deficits in memory and cognitive functions. The accumulation of amyloid beta peptide ($A{\beta}$) and oxidative stress in the brain are the most common causes of AD. MATERIALS/METHODS: Caffeic acid (CA) is an active phenolic compound that has a variety of pharmacological actions. We studied the protective abilities of CA in an $A{\beta}_{25-35}$-injected AD mouse model. CA was administered at an oral dose of 10 or 50 mg/kg/day for 2 weeks. Behavioral tests including T-maze, object recognition, and Morris water maze were carried out to assess cognitive abilities. In addition, lipid peroxidation and nitric oxide (NO) production in the brain were measured to investigate the protective effect of CA in oxidative stress. RESULTS: In the T-maze and object recognition tests, novel route awareness and novel object recognition were improved by oral administration of CA compared with the $A{\beta}_{25-35}$-injected control group. These results indicate that administration of CA improved spatial cognitive and memory functions. The Morris water maze test showed that memory function was enhanced by administration of CA. In addition, CA inhibited lipid peroxidation and NO formation in the liver, kidney, and brain compared with the $A{\beta}_{25-35}$-injected control group. In particular, CA 50 mg/kg/day showed the stronger protective effect from cognitive impairment than CA 10 mg/kg/day. CONCLUSIONS: The present results suggest that CA improves $A{\beta}_{25-35}$-induced memory deficits and cognitive impairment through inhibition of lipid peroxidation and NO production.
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제안 방법
The T-maze test was conducted according to the procedure established by Montgomery [26]. A T-shaped maze consisting of a start box, left arm, and right arm (length of start and goal stems 76 cm, width 12 cm, height 20 cm) was constructed. The right arm was provided with a moveable blocking door made of black acrylic.
The Morris water maze task was performed to evaluate the effect of CA on spatial learning and memory. As shown in Fig.
Four posters on the walls of the apparatus provided visual cues for navigation. Three training trials were conducted each day for 3 days. In the training trials, the mice were placed in the pool facing the wall, and then from random starting points were allowed to swim and find the hidden platform.
Therefore, dietary intake and body weight did not affect the effect of CA on cognitive function in AD model. To evaluate the effect of CA on short-term spatial learning and memory, the T-maze task was carried out. Learning and memory were significantly impaired in mice injected with Aβ25-35, whereas the groups administered CA showed higher cognitive recognition towards the novel route.
대상 데이터
The experimental apparatus consisted of a pool (100 cm in diameter, 35 cm in height) that was randomly divided into four quadrants, filled with water maintained at 22 ± 1°C and made opaque using water-soluble nontoxic white paint.
데이터처리
T-maze test and novel object recognition data were performed by Student’s t-test for two-condition comparisons.
The statistical significance of experimental results was determined using one-way analysis of variance (ANOVA), followed by Duncan’s multiple tests.
이론/모형
Malondialdehyde (MDA) levels were measured using the method described by Ohkawa [29]. After completion of the behavioral tests, mice were anesthetized using CO2 gas.
The NO concentration in tissues was determined by the method of Schmidt [30]. Briefly, 150 μl of tissue homogenate was mixed with 130 μl of distilled water, and 20 μl of the mixed solution was added to the same amount of phosphoric acid and 0.
The T-maze test was conducted according to the procedure established by Montgomery [26]. A T-shaped maze consisting of a start box, left arm, and right arm (length of start and goal stems 76 cm, width 12 cm, height 20 cm) was constructed.
성능/효과
In conclusion, we confirmed that oral administration of CA at 10 and 50 mg/kg/day protected against Aβ and oxidative stress in an AD mouse model.
참고문헌 (56)
1 Tsunekawa H Noda Y Mouri A Yoneda F Nabeshima T Synergistic effects of selegiline and donepezil on cognitive impairment induced by amyloid beta (25-35) Behav Brain Res 2008 190 224 232 18420288
4 Takahata K Minami A Kusumoto H Shimazu S Yoneda F Effects of selegiline alone or with donepezil on memory impairment in rats Eur J Pharmacol 2005 518 140 144 16061218
5 Rottkamp CA Raina AK Zhu X Gaier E Bush AI Atwood CS Chevion M Perry G Smith MA Redox-active iron mediates amyloid-beta toxicity Free Radic Biol Med 2001 30 447 450 11182300
6 Nunomura A Castellani RJ Zhu X Moreira PI Perry G Smith MA Involvement of oxidative stress in Alzheimer disease J Neuropathol Exp Neurol 2006 65 631 641 16825950
7 Avdulov NA Chochina SV Igbavboa U O'Hare EO Schroeder F Cleary JP Wood WG Amyloid beta-peptides increase annular and bulk fluidity and induce lipid peroxidation in brain synaptic plasma membranes J Neurochem 1997 68 2086 2091 9109536
8 Butterfield DA Beta-amyloid-associated free radical oxidative stress and neurotoxicity: implications for Alzheimer's disease Chem Res Toxicol 1997 10 495 506 9168246
9 Butterfield DA Amyloid beta-peptide (1-42)-induced oxidative stress and neurotoxicity" implications for neurodegeneration in Alzheimer's disease brain. A review Free Radic Res 2002 36 1307 1313 12607822
10 Markesbery WR Carney JM Oxidative alterations in Alzheimer's disease Brain Pathol 1999 9 133 146 9989456
11 Behl C Davis J Cole GM Schubert D Vitamin E protects nerve cells from amyloid beta protein toxicity Biochem Biophys Res Commun 1992 186 944 950 1497677
13 Butterfield D Castegna A Pocernich C Drake J Scapagnini G Calabrese V Nutritional approaches to combat oxidative stress in Alzheimer's disease J Nutr Biochem 2002 13 444 461 12165357
14 Moridani MY Scobie H Jamshidzadeh A Salehi P O'Brien PJ Caffeic acid, chlorogenic acid, and dihydrocaffeic acid metabolism: glutathione conjugate formation Drug Metab Dispos 2001 29 1432 1439 11602518
17 U Rehman M Sultana S Attenuation of oxidative stress, inflammation and early markers of tumor promotion by caffeic acid in Fe-NTA exposed kidneys of Wistar rats Mol Cell Biochem 2011 357 115 124 21647614
18 Roos TU Heiss EH Schwaiberger AV Schachner D Sroka IM Oberan T Vollmar AM Dirsch VM Caffeic acid phenethyl ester inhibits PDGF-induced proliferation of vascular smooth muscle cells via activation of p38 MAPK, HIF-1α, and heme oxygenase-1 J Nat Prod 2011 74 352 356 21265554
19 Scapagnini G Vasto S Abraham NG Caruso C Zella D Fabio G Modulation of Nrf2/ARE pathway by food polyphenols: a nutritional neuroprotective strategy for cognitive and neurodegenerative disorders Mol Neurobiol 2011 44 192 201 21499987
20 Eom TK Ryu B Lee JK Byun HG Park SJ Kim SK β-secretase inhibitory activity of phenolic acid conjugated chitooligosaccharides J Enzyme Inhib Med Chem 2013 28 214 217 22424182
21 Sul D Kim HS Lee D Joo SS Hwang KW Park SY Protective effect of caffeic acid against beta-amyloid-induced neurotoxicity by the inhibition of calcium influx and tau phosphorylation Life Sci 2009 84 257 262 19101570
22 Khan KA Kumar N Nayak PG Nampoothiri M Shenoy RR Krishnadas N Rao CM Mudgal J Impact of caffeic acid on aluminium chloride-induced dementia in rats J Pharm Pharmacol 2013 65 1745 1752 24236984
23 Muthaiyah B Essa MM Lee M Chauhan V Kaur K Chauhan A Dietary supplementation of walnuts improves memory deficits and learning skills in transgenic mouse model of Alzheimer's disease J Alzheimers Dis 2014 42 1397 1405 25024344
24 Maurice T Lockhart BP Privat A Amnesia induced in mice by centrally administered β-amyloid peptides involves cholinergic dysfunction Brain Res 1996 706 181 193 8822355
25 Laursen SE Belknap JK Intracerebroventricular injections in mice. Some methodological refinements J Pharmacol Methods 1986 16 355 357 3784576
26 Montgomery KC A test of two explanations of spontaneous alternation J Comp Physiol Psychol 1952 45 287 293 14946277
27 Bevins RA Besheer J Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study 'recognition memory' Nat Protoc 2006 1 1306 1311 17406415
30 Schmidt HH Warner TD Nakane M Förstermann U Murad F Regulation and subcellular location of nitrogen oxide synthases in RAW264.7 macrophages Mol Pharmacol 1992 41 615 624 1373797
31 Bachman DL Wolf PA Linn RT Knoefel JE Cobb JL Belanger AJ White LR D'Agostino RB Incidence of dementia and probable Alzheimer's disease in a general population: the Framingham Study Neurology 1993 43 515 519 8450993
32 Lu P Mamiya T Lu L Mouri A Ikejima T Kim HC Zou LB Nabeshima T Xanthoceraside attenuates amyloid β peptide(25-35)-induced learning and memory impairments in mice Psychopharmacology (Berl) 2012 219 181 190 21735075
33 Kubo T Nishimura S Kumagae Y Kaneko I In vivo conversion of racemized beta-amyloid ([D-Ser 26]A beta 1-40) to truncated and toxic fragments ([D-Ser 26]A beta 25-35/40) and fragment presence in the brains of Alzheimer's patients J Neurosci Res 2002 70 474 483 12391608
34 Mattson MP Begley JG Mark RJ Furukawa K Abeta25-35 induces rapid lysis of red blood cells: contrast with Aβ1-42 and examination of underlying mechanisms Brain Res 1997 771 147 153 9383018
35 Barnham KJ Masters CL Bush AI Neurodegenerative diseases and oxidative stress Nat Rev Drug Discov 2004 3 205 214 15031734
36 Wypijewska A Galazka-Friedman J Bauminger ER Wszolek ZK Schweitzer KJ Dickson DW Jaklewicz A Elbaum D Friedman A Iron and reactive oxygen species activity in parkinsonian substantia nigra Parkinsonism Relat Disord 2010 16 329 333 20219408
37 Choi SJ Kim MJ Heo HJ Kim JK Jun WJ Kim HK Kim EK Kim MO Cho HY Hwang HJ Kim YJ Shin DH Ameliorative effect of 1,2-benzenedicarboxylic acid dinonyl ester against amyloid beta peptide-induced neurotoxicity Amyloid 2009 16 15 24 19291510
38 Salah N Miller NJ Paganga G Tijburg L Bolwell GP Rice-Evans C Polyphenolic flavanols as scavengers of aqueous phase radicals and as chain-breaking antioxidants Arch Biochem Biophys 1995 322 339 346 7574706
39 Ono K Hasegawa K Naiki H Yamada M Anti-amyloidogenic activity of tannic acid and its activity to destabilize Alzheimer's beta-amyloid fibrils in vitro Biochim Biophys Acta 2004 1690 193 202 15511626
40 Ono K Yoshiike Y Takashima A Hasegawa K Naiki H Yamada M Potent anti-amyloidogenic and fibril-destabilizing effects of polyphenols in vitro : implications for the prevention and therapeutics of Alzheimer's disease J Neurochem 2003 87 172 181 12969264
41 Chung TW Moon SK Chang YC Ko JH Lee YC Cho G Kim SH Kim JG Kim CH Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism FASEB J 2004 18 1670 1681 15522912
42 Huang Y Jin M Pi R Zhang J Chen M Ouyang Y Liu A Chao X Liu P Liu J Ramassamy C Qin J Protective effects of caffeic acid and caffeic acid phenethyl ester against acrolein-induced neurotoxicity in HT22 mouse hippocampal cells Neurosci Lett 2013 535 146 151 23313590
44 Roher AE Esh CL Kokjohn TA Castaño EM Van Vickle GD Kalback WM Patton RL Luehrs DC Daugs ID Kuo YM Emmerling MR Soares H Quinn JF Kaye J Connor DJ Silverberg NB Adler CH Seward JD Beach TG Sabbagh MN Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer's disease Alzheimers Dement 2009 5 18 29 19118806
45 Selkoe DJ Podlisny MB Joachim CL Vickers EA Lee G Fritz LC Oltersdorf T Beta-amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues Proc Natl Acad Sci U S A 1988 85 7341 7345 3140239
46 Sandbrink R Masters CL Beyreuther K Beta A4-amyloid protein precursor mRNA isoforms without exon 15 are ubiquitously expressed in rat tissues including brain, but not in neurons J Biol Chem 1994 269 1510 1517 8288617
47 Butterfield DA Boyd-Kimball D Amyloid beta-peptide(1-42) contributes to the oxidative stress and neurodegeneration found in Alzheimer disease brain Brain Pathol 2004 14 426 432 15605990
48 Cotman CW Su JH Mechanisms of neuronal death in Alzheimer's disease Brain Pathol 1996 6 493 506 8944319
49 Choi JY Cho EJ Lee HS Lee JM Yoon YH Lee S Tartary buckwheat improves cognition and memory function in an in vivo amyloid-β-induced Alzheimer model Food Chem Toxicol 2013 53 105 111 23219778
50 Lee AY Yamabe N Kang KS Kim HY Lee S Cho EJ Cognition and memory function of Taraxacum coreanum in an in vivo amyloid-β-induced mouse model of Alzheimer's disease Arch Biol Sci 2014 66 1357 1366
51 Choi YY Maeda T Fujii H Yokozawa T Kim HY Cho EJ Shibamoto T Oligonol improves memory and cognition under an amyloid β(25-35)-induced Alzheimer's mouse model Nutr Res 2014 34 595 603 25150118
52 Soliman KF Mazzio EA In vitro attenuation of nitric oxide production in C6 astrocyte cell culture by various dietary compounds Proc Soc Exp Biol Med 1998 218 390 397 9714085
53 Yan JJ Cho JY Kim HS Kim KL Jung JS Huh SO Suh HW Kim YH Song DK Protection against β-amyloid peptide toxicity in vivo with long-term administration of ferulic acid Br J Pharmacol 2001 133 89 96 11325798
54 Manach C Scalbert A Morand C Rémésy C Jiménez L Polyphenols: food sources and bioavailability Am J Clin Nutr 2004 79 727 747 15113710
55 National Institute of Food and Drug Safety Evaluation (KR) Tox-Info. Caffeic acid. [internet] Cheongju National Institute of Food and Drug Safety Evaluation 2015 cited 2015 March 22 Available from: http://www.nifds.go.kr/toxinfo/index
56 Shinomiya K Omichi J Ohnishi R Ito H Yoshida T Kamei C Effects of chlorogenic acid and its metabolites on the sleep-wakefulness cycle in rats Eur J Pharmacol 2004 504 185 189 15541420
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