昆仑雪菊水溶性黄酮提取物对D-半乳糖致衰老小鼠学习记忆障碍的改善作用
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摘要
为探讨昆仑雪菊水溶性黄酮提取物(water soluble flavonoids from Coreopsis tinctoria flowers,CTWF)对D-半乳糖致衰老小鼠学习记忆障碍的影响,以SPF级昆明种小鼠为实验对象,随机分为正常组、衰老模型组、VE组(50 mg/(kg·d))和CTWF低、高剂量组(150、600 mg/(kg·d))。除正常组皮下注射生理盐水外,其余各组均注射D-半乳糖(300 mg/(kg·d)),连续42 d造模,注射1 h后,药物组分别灌胃VE和不同剂量CTWF,正常组和模型组灌胃等量生理盐水。采用Morris水迷宫测试各组小鼠学习记忆能力,并测定小鼠脑组织乙酰胆碱(acetylcholine,Ach)含量,乙酰胆碱酯酶(acetylcholinesterase,AchE)、超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathioneperoxidase,GSH-Px)活力和丙二醛(malondialdehyde,MDA)含量。结果表明:CTWF能够显著提升衰老模型小鼠的学习记忆能力(P<0.05),并显著提高脑组织SOD、GSH-Px活力和Ach含量(P<0.05),降低AchE活力和MDA含量(P<0.05)。因此,CTWF具有明显改善衰老模型小鼠学习记忆障碍的作用,其机制可能与提高脑组织胆碱能系统功能和减少自由基损伤有关。
Our aim in this study was to investigate the effects and mechanisms of water soluble flavonoids from Coreopsis tinctoria flowers(CTWF) on learning and memory ability in D-galactose-induced aging mice. Specific pathogen-free(SPF) Kunming mice were randomly divided into control, aging model, VE(50 mg/(kg·d)), and CTWF low-and high-dose groups(150 and 600 mg/(kg·d)). The mice in the control group were injected subcutaneously with normal saline while the mice in the other groups were successively injected with D-galactose(300 g/(kg·d)) for 42 days. At 1 hour after injection, the drug treatment groups were intragastrically administrated with VE and different dosage of CTWF while the mice from the control and model groups were administrated with an equal volume of normal saline. Learning and memory abilities were detected by Morris water maze test, and acetylcholinesterase(AchE), superoxide dismutase(SOD), and glutathione peroxidase(GSH-Px) activities, and acetylcholine(Ach) and malondialdehyde(MDA) contents in brain tissues were measured. Results showed that CTWF significantly improved the learning and memory abilities of aging mice(P < 0.05), elevated SOD and GSH-Px activities and Ach content(P < 0.05), and reduced AchE activity and MDA content(P < 0.05). In conclusion, CTWF has a significant effect on improving D-galactose-induced learning and memory disorders in mice, and its mechanism may be related to enhanced cholinergic system function and reduced free radical-induced damage in brain tissues of mice.
Our aim in this study was to investigate the effects and mechanisms of water soluble flavonoids from Coreopsis tinctoria flowers(CTWF) on learning and memory ability in D-galactose-induced aging mice. Specific pathogen-free(SPF) Kunming mice were randomly divided into control, aging model, VE(50 mg/(kg·d)), and CTWF low-and high-dose groups(150 and 600 mg/(kg·d)). The mice in the control group were injected subcutaneously with normal saline while the mice in the other groups were successively injected with D-galactose(300 g/(kg·d)) for 42 days. At 1 hour after injection, the drug treatment groups were intragastrically administrated with VE and different dosage of CTWF while the mice from the control and model groups were administrated with an equal volume of normal saline. Learning and memory abilities were detected by Morris water maze test, and acetylcholinesterase(AchE), superoxide dismutase(SOD), and glutathione peroxidase(GSH-Px) activities, and acetylcholine(Ach) and malondialdehyde(MDA) contents in brain tissues were measured. Results showed that CTWF significantly improved the learning and memory abilities of aging mice(P < 0.05), elevated SOD and GSH-Px activities and Ach content(P < 0.05), and reduced AchE activity and MDA content(P < 0.05). In conclusion, CTWF has a significant effect on improving D-galactose-induced learning and memory disorders in mice, and its mechanism may be related to enhanced cholinergic system function and reduced free radical-induced damage in brain tissues of mice.
引文
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[22]SONG Jia,CHU Shuaishuai,CUI Yin,et al.Circadian rhythm resynchronization improved isoflurane-induced cognitive dysfunction in aged mice[J].Experimental Neurology,2018,306:45-54.DOI:10.1016/j.expneurol.2018.04.009.
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[24]张丽梅,程永强,宋曙辉.紫山药多糖对D-半乳糖衰老模型大鼠肝、脑的影响[J].食品科学,2017,38(13):196-200.DOI:10.7506/spkx1002-6630-201713032.
[25]ZHOU Xuanxuan,YANG Qian,XIE Yanhua,et al.Protective effect of tetrahydroxystilbene glucoside against D-galactose induced aging process in mice[J].Phytochemistry Letters,2013,6(3):372-378.DOI:10.1016/j.phytol.2013.05.002.
[26]LI Jiejia,ZHU Qing,LU Yapeng,et al.Ligustilide prevents cognitive impairment and attenuates neurotoxicity in D-galactose induced aging mice brain[J].Brain Research,2015,1595:19-28.DOI:10.1016/j.brainres.2014.10.012.
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[30]GANDHI S,ABRAMOV A Y.Mechanism of oxidative stress in neurodegeneration[J].Oxidative Medicine and Cellular Longevity,2012,2012(3):1-11.DOI:10.1155/2012/428010.
[31]HARIPRIYA D,SANGEETHA P,KANCHANA A,et al.Modulation of age-associated oxidative DNA damage in rat brain cerebral cortex,striatum and hippocampus by L-carnitine[J].Experimental Gerontology,2005,40(3):129-135.DOI:10.1016/j.exger.2004.10.006.
[32]陈君,杨光,刘文群.小鼠抗衰老实验及微生物抗衰老研究概况[J].中国酿造,2011,30(6):13-16.DOI:10.3969/j.issn.0254-5071.2011.06.004.
[33]CUI Junjian,YUAN Jiangfeng,ZHANG Zhiqi,et al.Anti-oxidation activity of the crude polysaccharides isolated from Polygonum Cillinerve(Nakai)Ohwi in immunosuppressed mice[J].Journal of Ethnopharmacology,2010,132(2):512-517.DOI:10.1016/j.jep.2010.08.052.
[2]BEKTAS A,SCHURMAN S H,SEN R,et al.Aging inflammation and the environment[J].Experimental Gerontology,2018,105:10-18.DOI:10.1016/j.exger.2017.12.015.
[3]马莹娟,尚玉莹,王德杰,等.柿叶黄酮类化合物对D-半乳糖致衰老小鼠的抗炎抗氧化神经保护作用[J].复旦学报(医学版),2015,42(1):7-12;30.DOI:10.3969/j.issn.1672-8467.2015.01.002.
[4]明建,曾凯芳,吴素蕊,等.天麻多糖PGEB-3-H对东莨菪碱所致小鼠学习记忆障碍的影响[J].食品科学,2010,31(3):246-249.
[5]GUO Limin,ZHANG Wensheng,LI Shiming,et al.Chemical and nutraceutical properties of Coreopsis tinctoria[J].Journal of Functional Foods,2015,13(4):11-20.DOI:10.1016/j.jff.2014.11.011.
[6]过利敏,张平,张谦,等.雪菊化学成分分析、提取、鉴定及其生物活性研究进展[J].食品科学,2014,35(7):298-304.DOI:10.7506/spkx1002-6630-201407058.
[7]LAM S C,LIU Xin,CHEN Xianqiang,et al.Chemical characteristics of different partsof Coreopsis tinctoria in China using microwaveassisted extraction and high-performance liquid chromatography followed by chemometric analysis[J].Journal of Separation Science,2016,39(15):2919-2927.DOI:10.1002/jssc.201600365.
[8]LI Yali,CHEN Xinmei,XUE Jie,et al.Flavonoids from Coreopsis tinctoria adjust lipid metabolism in hyperlipidemia animals by downregulating adipose differentiation-related protein[J].Lipids in Health and Disease,2014,13(1):193-200.DOI:10.1186/1476-511X-13-193.
[9]DIAS T,MOTAFILIPE H,LIU B,et al.Recovery of oral glucose tolerance by Wistar rats after treatment with Coreopsis tinctoria infusion[J].Phytotherapy Research,2010,24(5):699-705.DOI:10.1002/ptr.2998.
[10]YAO Xincheng,GU Chengzhi,TIAN Liping,et al.Comparative study on the antioxidant activities of extracts of Coreopsis tinctoria flowering tops from Kunlun Mountains,Xinjiang,north-western China[J].Natural Product Research,2016,30(4):429-432.DOI:10.1080/14786419.2015.1015019.
[11]WANG Wei,CHEN Wei,YANG Yingshi,et al.New phenolic compounds from Coreopsis tinctoria Nutt.and their antioxidant and angiotensin I-converting enzyme inhibitory activities[J].Journal of Agricultural and Food Chemistry,2015,63(1):200-207.DOI:10.1021/jf504289g.
[12]ZHANG Yuan,SHI Shepo,ZHAO Mingbo,et al.Coreosides A-D,C14-polyacetylene glycosides from the capitula of Coreopsis tinctoria and its anti-inflammatory activity against COX-2[J].Fitoterapia,2013,87(1):93-97.DOI:10.1016/j.fitote.2013.03.024.
[13]ZHI Qi,LI Yao,LI Fuhua,et al.The protective effect of polyphenols extracted from the buds of Coreopsis tinctoria against D-galactosamine/lipopolysaccharide-induced acute liver damage in mice[J].Journal of Functional Foods,2018,44:201-208.DOI:10.1016/j.jff.2018.03.019.
[14]YANG Qiang,SUN Yuhua,ZHANG Li,et al.Antihypertensive effects of extract from flower buds of Coreopsis tinctoria on spontaneously hypertensive rats[J].Chinese Herbal Medicines,2014,6(2):103-109.DOI:10.1016/S1674-6384(14)60015-0.
[15]SUN Yuhua,ZHAO Jun,JIN Hongtao,et al.Vasorelaxant effects of the extracts and some flavonoids from the buds of Coreopsis tinctoria[J].Pharmaceutical Biology,2013,51(9):1158-1164.DOI:10.3109/13880209.2013.782320.
[16]沙爱龙,吴瑛,盛海燕,等.昆仑雪菊黄酮对衰老模型小鼠脑及脏器指数的影响[J].动物医学进展,2013,34(7):66-68.DOI:10.3969/j.issn.1007-5038.2013.07.014.
[17]ZHANG Weixin,HAO Haiyan,SHA Ailong.Effects of the Coreopsis tinctoria extracts on anti-aging in the aging model mice[J].Indian Journal of Animal Research,2016,50(5):769-772.DOI:10.18805/ijar.9630.
[18]LI Ning,MENG Dali,PAN Ying,et al.Anti-neuroinflammatory and NQO1 inducing activity of natural phytochemicals from Coreopsis tinctoria[J].Journal of Functional Foods,2015,17:837-846.DOI:10.1016/j.jff.2015.06.027.
[19]吴瑛,刘天志,袁守亮.新疆高寒香菊总黄酮、多酚及水浸出物含量分析[J].食品科技,2012,37(8):186-188;192.DOI:10.13684/j.cnki.spkj.2012.08.031.
[20]吴瑛,王秀芳,袁守亮.响应面分析昆仑雪菊水溶性黄酮类化合物的提取工艺[J].食品科学,2013,34(6):129-133.DOI:10.7506/spkx1002-6630-201306028.
[21]LIANG Qiang,CUI Jun,LI Hang,et al.Florets of sunflower(Helianthus annuus L.):potential new sources of dietary fiber and phenolic acids[J].Journal of Agricultural and Food Chemistry,2013,61(14):3435-3442.DOI:10.1021/jf400569a.
[22]SONG Jia,CHU Shuaishuai,CUI Yin,et al.Circadian rhythm resynchronization improved isoflurane-induced cognitive dysfunction in aged mice[J].Experimental Neurology,2018,306:45-54.DOI:10.1016/j.expneurol.2018.04.009.
[23]陈燏,刘洪吉,尤倩倩,等.活性肽-N对D-半乳糖致衰老小鼠的作用效果[J].食品科学,2018,39(1):178-184.DOI:10.7506/spkx1002-6630-201801027.
[24]张丽梅,程永强,宋曙辉.紫山药多糖对D-半乳糖衰老模型大鼠肝、脑的影响[J].食品科学,2017,38(13):196-200.DOI:10.7506/spkx1002-6630-201713032.
[25]ZHOU Xuanxuan,YANG Qian,XIE Yanhua,et al.Protective effect of tetrahydroxystilbene glucoside against D-galactose induced aging process in mice[J].Phytochemistry Letters,2013,6(3):372-378.DOI:10.1016/j.phytol.2013.05.002.
[26]LI Jiejia,ZHU Qing,LU Yapeng,et al.Ligustilide prevents cognitive impairment and attenuates neurotoxicity in D-galactose induced aging mice brain[J].Brain Research,2015,1595:19-28.DOI:10.1016/j.brainres.2014.10.012.
[27]TUCKER L B,VELOSKY A G,MCCABE J T,et al.Applications of the Morris water maze in translational traumatic brain injury research[J].Neuroscience and Biobehavioral Reviews,2018,88:187-200.DOI:10.1016/j.neubiorev.2018.03.010.
[28]MOHAPEL P,LEANZA G,KOKAIA M,et al.Forebrain acetylcholine regulates adult hippocampal neurogenesis and learning[J].Neurobiology of Aging,2005,26(6):939-946.DOI:10.1016/j.neurobiolaging.2004.07.015.
[29]赵玲,刘丽,张兰,等.不同时程的脑缺血对大鼠学习记忆功能及脑皮层乙酰胆碱酯酶活性的影响[J].中国比较医学杂志,2006,16(2):81-84.DOI:10.3969/j.issn.1671-7856.2006.02.005.
[30]GANDHI S,ABRAMOV A Y.Mechanism of oxidative stress in neurodegeneration[J].Oxidative Medicine and Cellular Longevity,2012,2012(3):1-11.DOI:10.1155/2012/428010.
[31]HARIPRIYA D,SANGEETHA P,KANCHANA A,et al.Modulation of age-associated oxidative DNA damage in rat brain cerebral cortex,striatum and hippocampus by L-carnitine[J].Experimental Gerontology,2005,40(3):129-135.DOI:10.1016/j.exger.2004.10.006.
[32]陈君,杨光,刘文群.小鼠抗衰老实验及微生物抗衰老研究概况[J].中国酿造,2011,30(6):13-16.DOI:10.3969/j.issn.0254-5071.2011.06.004.
[33]CUI Junjian,YUAN Jiangfeng,ZHANG Zhiqi,et al.Anti-oxidation activity of the crude polysaccharides isolated from Polygonum Cillinerve(Nakai)Ohwi in immunosuppressed mice[J].Journal of Ethnopharmacology,2010,132(2):512-517.DOI:10.1016/j.jep.2010.08.052.