Effects and mechanisms of Tieguanyin on the behavior of Alzheimer’s disease APP/PS1 mice

doi:10.3785/j.issn.1008-9209.2021.05.191

Journal of Zhejiang University (Agriculture and Life Sciences)

2022, Vol. 48

Issue (1): 68-77 DOI: 10.3785/j.issn.1008-9209.2021.05.191

Animal sciences & veterinary medicines

Effects and mechanisms of Tieguanyin on the behavior of Alzheimer’s disease APP/PS1 mice

Hyunuk KANG¹(

),Hui ZHOU¹,Yushan YE¹,Zhonghua LIU²,Yuede WEI³,Jiangfan YANG⁴,Eunhye KIM¹,Puming HE¹,Bo LI¹,Yuanyuan WU¹,Youying TU¹(

)

^1.Department of Tea Science, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China
^2.Key Laboratory of Tea Science of Education of Ministry, Hunan Agricultural University, Changsha 410128, China
^3.Fujian Anxi Qishan Weiyin Famous Tea Co. , Ltd. , Quanzhou 362431, Fujian, China
^4.College of Horticulture, Fujian Agriculture and Forestry University, Fuzhou 350002, China

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Abstract

The effects of Tieguanyin extracts from different fragrance types (Qingxiang, Tgy-Q; Nongxiang, Tgy-N; and Chenxiang, Tgy-C) on the behavior of APP/PS1 double transgenic Alzheimer’s disease (AD) mice were studied, and the mechanisms of oxidative stress and inflammation were analyzed. Forty six-month-old female APP/PS1 mice were equally divided into five groups, which named as model group, donepezil group, Tgy-Q, Tgy-N and Tgy-C groups, and the control group consisted of 10 C57BL/6J mice. The drug was given by oral gavage for 70 consecutive days, and Y-maze test and open field test were performed during administration. At the end of the behavioral study, they were executed, and their plasma and brain tissue were collected, and then the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) content in plasma of mice were determined, and the morphological changes of glial cells were observed by immunohistochemical assay. The spontaneous alternation behavior rates of Tgy-Q, Tgy-N, Tgy-C extract treatments in the Y-maze experiment of mice groups were increased by 17.3%, 17.6% and 19.8% compared with the model group, respectively (P＜0.001), and the learning and memory abilities of mice in each group were significantly improved as compared with the model group. The results of open field test showed that the movement distances and residence time in the central area of mice fed with Tieguanyin extracts were significantly increased. The effective movement distances in the central area of mice was increased by 93.0% in the Tgy-C group (P＜0.001), followed by 82.0% in the Tgy-N group (P＜0.001) and 49.2% in the Tgy-Q group (P＜0.001). The optimal retention time in the central area of mice was 105.0% in the Tgy-C group (P＜0.01), followed by 84.1% in the Tgy-N group (P＜0.01), and 66.8% in the Tgy-Q group (P＜0.05). In the open field test, the spatial exploration ability and anxiety behavior of Tgy-C group were the best in all the treatments. In this experiment, oxidative stress levels of three Tieguanyin treatments were decreased, which are the main mechanisms of Tieguanyin against Alzheimer’s disease of APP/PS1 mice. Compared with the model group, the MDA contents of plasma in the Tgy-Q, Tgy-N, Tgy-C treatments were significantly reduced by 18.44%, 12.97% and 15.11%, respectively, and the SOD activities in the three groups were increased by 15.31%, 13.69% and 18.80%, respectively. Tieguanyin extracts also improved the morphological recovery of microglia and astrocytes in the brain of AD mice. The above research results indicate that three Tieguanyin extracts had a certain alleviating or protective effect on AD mice.

Key words： Tieguanyin with different fragrance types Alzheimer’s disease cognitive function oxidative stress inflammation

Received: 19 May 2021 Published: 04 March 2022

CLC:

S 571.1

Corresponding Authors: Youying TU E-mail: 11616111@zju.edu.cn;youytu@zju.edu.cn

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	Hyunuk KANG
	Hui ZHOU
	Yushan YE
	Zhonghua LIU
	Yuede WEI
	Jiangfan YANG
	Eunhye KIM
	Puming HE
	Bo LI
	Yuanyuan WU
	Youying TU

Cite this article:

Hyunuk KANG,Hui ZHOU,Yushan YE,Zhonghua LIU,Yuede WEI,Jiangfan YANG,Eunhye KIM,Puming HE,Bo LI,Yuanyuan WU,Youying TU. Effects and mechanisms of Tieguanyin on the behavior of Alzheimer’s disease APP/PS1 mice. Journal of Zhejiang University (Agriculture and Life Sciences), 2022, 48(1): 68-77.

URL:

https://www.zjujournals.com/agr/10.3785/j.issn.1008-9209.2021.05.191 OR https://www.zjujournals.com/agr/Y2022/V48/I1/68

铁观音对阿尔茨海默病小鼠行为的影响及机制

研究清香型铁观音（Tgy-Q）、浓香型铁观音（Tgy-N）和陈香型铁观音（Tgy-C）对APP/PS1双转基因阿尔茨海默病（Alzheimer’s disease, AD）小鼠行为学的改善作用，及其对AD小鼠氧化应激及炎症等的作用机制。以C57BL/6J小鼠10只作为对照，6月龄雌性APP/PS1小鼠40只分成模型组、多奈哌齐组、Tgy-Q、Tgy-N和Tgy-C组，连续70 d灌胃给药，进行Y迷宫和旷场行为学实验，结束后处死，收集血浆和脑组织，检测小鼠血浆中超氧化物歧化酶活性、谷胱甘肽过氧化物酶活性和丙二醛含量，并通过免疫组化实验观察胶质细胞的形态变化。Y迷宫实验结果表明，3组铁观音提取物处理组小鼠自发交替反应率分别比模型组增加17.3%、17.6%、19.8%（P＜0.001），各组小鼠工作记忆能力较模型组有显著提高。旷场实验结果发现：与模型组相比，Tgy-C组小鼠中央区域的运动距离增加93.0%，Tgy-N组增加82.0%，Tgy-Q组增加49.2%；中央区域停留时间以Tgy-C组小鼠的效果最佳，增加105.0%（P＜0.01），其次为Tgy-N组，增加84.1%（P＜0.01），Tgy-Q组增加66.8%（P＜0.05）。Tgy-C组小鼠的空间探索能力及焦虑行为改善更好。本实验中氧化应激水平下降是抗AD作用的主要作用机制。研究发现，与模型组组比，Tgy-Q、Tgy-N、Tgy-C处理的小鼠血浆丙二醛含量分别降低18.44%、12.97%、15.11%；超氧化物歧化酶活性分别升高15.31%、13.69%、18.80%。免疫组化实验结果表明，3种铁观音提取物对AD小鼠脑部小胶质细胞和星型胶质细胞形态的恢复有改善作用。综上所述，铁观音提取物对AD小鼠模型具有一定的缓解或保护作用，为科学饮用铁观音提取物抗AD功效提供了新的理论依据。

关键词： 不同香型铁观音, 阿尔茨海默病, 认知功能, 氧化应激, 炎症

Table 1 Detailed regimen for intragastric administration of the tested mice

Fig. 1 Effect of Tieguanyin extracts on spontaneous alternation behavior of APP/PS1 mice in the Y-maze testA. Control group; B. Model group; C. Donepezil group; D. Tgy-Q group; E. Tgy-N group; F. Tgy-C group (The same below). Compared with the control group, triple pound signs (###) indicate extremely significant differences at the 0.001 probability level; compared with the model group, double asterisks (**) and triple asterisks (***) indicate highly significant and extremely significant differences at the 0.01 and 0.001 probability levels, respectively.

Fig. 2 Total run distances of six groups of miceCompared with the control group, triple pound signs (###) indicate extremely significant differences at the 0.001 probability level; compared with the model group, double asterisks (**) indicate highly significant differences at the 0.01 probability level.

Fig. 3 Total run distances and time in central area of six groups of miceCompared with the control group, triple pound signs (###) indicate extremely significant differences at the 0.001 probability level; compared with the model group, single asterisk (*), double asterisks (**) and triple asterisks (***) indicate significant, highly significant and extremely significant differences at the 0.05, 0.01 and 0.001 probability levels, respectively.

Fig. 4 Trajectory maps of open field test of six groups of mice

Fig. 5 Effects of Tieguanyin extracts on the anti-oxidative abilities of blood plasma in APP/PS1 miceCompared with the control group, double pound signs (##) and triple pound signs (###) indicate highly significant and extremely significant differences at the 0.01 and 0.001 probability levels, respectively; compared with the model group, single asterisk (*), double asterisks (**) and triple asterisks (***) indicate significant, highly significant and extremely significant differences at the 0.05, 0.01 and 0.001 probability levels, respectively.

Fig. 6 Effects of Tieguanyin extracts on expression of GFAP in the brain of APP/PS1 mice by immunohistochemical staining

Fig. 7 Effects of Tieguanyin extracts on expression of Iba-1 in the brain of APP/PS1 mice by immunohistochemical staining


[1]	SUPNET C , BEZPROZVANNY I . Presenilins function in ER calcium leak and Alzheimer’s disease pathogenesis[J]. Cell Calcium, 2011, 50(3): 303-309. DOI:10.1016/j.ceca.2011.05.013 doi: 10.1016/j.ceca.2011.05.013

[2]	PATTERSON C . World Alzheimer report 2018: the state of the art of dementia research: new frontiers[R]. London, U.K.: Alzheimer’s Disease International (ADI), 2018: 6-7.

[3]	李昂 .2010—2050年中国老年痴呆的预测研究[D].江苏,苏州:苏州大学,2015. LI A . Dementia in China (2010—2050) estimated using the 2010 census[D]. Suzhou, Jiangsu: Soochow University, 2015. (in Chinese with English abstract)

[4]	WANG F , MICHAEL Y H S , SHUI T Y , et al . Neuroactive flavonoids interacting with GABAA receptor complex[J]. Current Drug Targets-CNS & Neurological Disorders, 2005, 4(5): 575-585. DOI:10.2174/156800705774322030 doi: 10.2174/156800705774322030

[5]	MACCIONI R B , ROJO L E , FERNANDEZ J A , et al . The role of neuroimmunomodulation in Alzheimer’s disease[J]. Annals of the New York Academy of Sciences, 2009, 1153(1): 240-246. DOI:10.1111/j.1749-6632.2008.03972 doi: 10.1111/j.1749-6632.2008.03972

[6]	刘世贤,毛林飞,于凡,等 .阿尔茨海默病的发病机制及天然多酚类化合物的治疗机制研究进展[J].中国新药杂志,2017,26(23):2799-2804. LIU S X , MAO L F , YU F , et al . Pathogenesis of Alzheimer’s disease and the therapeutic mechanism of natural polyphenols[J]. Chinese Journal of New Drugs, 2017, 26(23): 2799-2804. (in Chinese with English abstract)

[7]	高水练,林郑和,郝志龙,等 .新旧工艺制成铁观音的品质化学比较[J].茶叶科学技术,2004(3):27-28. DOI:10.3969/j.issn.1007-4872.2004.03.013 GAO S L , LIN Z H , HAO Z L , et al . Chemical quality comparison of the Tieguanyin made by old and new technology[J]. Tea Science and Technology, 2004(3): 27-28. (in Chinese) doi: 10.3969/j.issn.1007-4872.2004.03.013

[8]	文祎 .安溪铁观音品质化学及抗炎功能研究[D].长沙:湖南农业大学,2018. WEN Y . The research on quality chemistry and anti-inflammatory of Anxi Tieguanyin tea[D]. Changsha: Hunan Agricultural University, 2018. (in Chinese with English abstract)

[9]	张正竹 .茶叶生物化学实验教程[M].北京:中国农业出版社,2009:115-117. DOI:10.3724/sp.j.1011.2008.01305 ZHANG Z Z . Tea Biochemistry Experiment Course[M]. Beijing: China Agriculture Press, 2009: 115-117. (in Chinese) doi: 10.3724/sp.j.1011.2008.01305

[10]	曲春香,沈颂东,王雪峰,等 .用考马斯亮蓝测定植物粗提液中可溶性蛋白质含量方法的研究[J].苏州大学学报(自然科学版),2006,22(2):82-85. DOI:10.3969/j.issn.1000-2073.2006.02.020 QU C X , SHEN S D , WANG X F , et al . Method research of measuring soluble protein contents of plant rough extraction using Coomassie Brilliant Blue[J]. Journal of Suzhou University (Natural Science Edition), 2006, 22(2): 82-85. (in Chinese) doi: 10.3969/j.issn.1000-2073.2006.02.020

[11]	张国权,罗崧方,黄建蓉,等 .三氯化铝比色法检测桑叶提取物总黄酮的研究[J].农产品加工,2018(4):52-54, 57. ZHANG G Q , LUO S F , HUANG J R , et al . Research on determination of total flavonoids in mulberry leaf extract by aluminum chloride colorimetry[J]. Agricultural Products Processing, 2018(4): 52-54, 57. (in Chinese)

[12]	全国茶业标准化技术委员会 . 茶叶中茶多酚和儿茶素类含量的检测方法: [S].北京:中国标准出版社,2018. DOI:10.19103/as.2017.0036.03 National Technical Committee 339 on Tea of Standardization Administration of China.Determination of Total Polyphenols and Catechins Content in Tea: GB/T 8313—2018[S]. Beijing: China Standard Press, 2018. (in Chinese) doi: 10.19103/as.2017.0036.03

[13]	王蝶 .茶叶对肥胖大鼠的减肥作用及机制研究[D].长沙:湖南农业大学,2012. DOI:10.1002/jsfa.5887 WANG D . Studies on anti-obesity effects of tea extracts on high fat diet induced obese rats and their potential mechanisms[D]. Changsha: Hunan Agricultural University, 2012. (in Chinese with English abstract) doi: 10.1002/jsfa.5887

[14]	SURYAVANSHI P S , UAGLE R R , YILMAZER H D , et al . GluN2C/GluN2D subunit-selective NMDA receptor potentiator CIQ reverses MK-801-induced impairment in prepulse inhibition and working memory in Y-maze test in mice[J]. British Journal of Pharmacology, 2014, 171(3): 799-809. DOI:10.1111/bph.12518 doi: 10.1111/bph.12518

[15]	LIU D , QIU H M , FEI H Z , et al . Histone acetylation and expression of mono-aminergic transmitters synthetases involved in CUS-induced depressive rats[J]. Experimental Biology and Medicine, 2014, 239(3): 330-336. DOI:10.1177/1535370213513987 doi: 10.1177/1535370213513987

[16]	HART P C , BERGNER C L , SMOLINSKY A N , et al . Experimental models of anxiety for drug discovery and brain research[M]. PROETZEL G, WILES M. Mouse Models for Drug Discovery. Methods in Molecular Biology. Vol. 1438. New York, U.S.: Humana Press, 2016: 271-291. DOI:10.1007/978-1-4939-3661-8_16 doi: 10.1007/978-1-4939-3661-8_16

[17]	NG T P, FENG L , NITI M , et al . Tea consumption and cognitive impairment and decline in older Chinese adults[J]. The American Journal of Clinical Nutrition, 2008, 88(1): 224-231. DOI:10.1093/ajcn/88.1.224 doi: 10.1093/ajcn/88.1.224

[18]	KAUR T , PATHAK C M , PANDHI P , et al . Effects of green tea extract on learning, memory, behavior and acetylcho-linesterase activity in young and old male rats[J]. Brain and Cognition, 2008, 67(1): 25-30. DOI:10.1016/j.bandc.2007.10.003 doi: 10.1016/j.bandc.2007.10.003

[19]	LI H Y , WU X K , WU Q , et al . Green tea polyphenols protect against okadaic acid-induced acute learning and memory impairments in rats[J]. Nutrition, 2014, 30(3): 337-342. DOI:10.1016/j.nut.2013.08.021 doi: 10.1016/j.nut.2013.08.021

[20]	VAFEIADOU K , VAUZOUR D , LEE H , et al . The citrus flavanone naringenin inhibits inflammatory signaling in glial cells and protects against neuroinflammatory injury[J]. Archives of Biochemistry and Biophysics, 2009, 484(1): 100-109. DOI:10.1016/j.abb.2009.01.016 doi: 10.1016/j.abb.2009.01.016

[21]	POLITO C A , CAI Z Y , SHI Y L , et al . Association of tea consumption with risk of Alzheimer’s disease and anti-beta-amyloid effects of tea[J]. Nutrients, 2018, 10(5): 655-682. DOI:10.3390/nu10050655 doi: 10.3390/nu10050655

[22]	G?TZ J , ITTNER L M , DAVID D C . Role of the protein Tau in Alzheimer’s disease[J]. Drug Discovery Today: Disease Mechanisms, 2005, 2(4): 395-400. DOI:10.1016/j.ddmec.2005.11.008 doi: 10.1016/j.ddmec.2005.11.008

[23]	LUO F , LIU J Y , YAN T H , et al . Salidroside alleviates cigarette smoke-induced COPD in mice[J]. Biomedicine & Pharmacotherapy, 2017, 86: 155-161. DOI:10.1016/j.biopha.2016.12.032 doi: 10.1016/j.biopha.2016.12.032

[24]	LI Q , ZHAO H F , ZHAO M , et al . Chronic green tea catechins administration prevents oxidative stress-related brain aging in C57BL/6J mice[J]. Brain Research, 2010, 1353: 28-35. DOI:10.1016/j.brainres.2010.07.074 doi: 10.1016/j.brainres.2010.07.074

[25]	CHEN L J , YANG X Q , JIAO H L , et al . Tea catechins protect against lead-induced ROS formation, mitochondrial dysfunction, and calcium dysregulation in PC12 cells[J]. Chemical Research in Toxicology, 2003, 16(9): 1155-1161. DOI:10.1021/tx0340605 doi: 10.1021/tx0340605

[26]	CLEMENTI M E , GIARDINA B , COLUCCI D , et al . Amyloid-beta peptide affects the oxygen dependence of erythrocyte metabolism: a role for caspase 3[J]. The International Journal of Biochemistry & Cell Biology, 2007, 39(4): 727-735. DOI:10.1016/j.biocel.2006.11.013 doi: 10.1016/j.biocel.2006.11.013

[27]	TANG S S , HONG H , CHEN L , et al . Involvement of cysteinyl leukotriene receptor 1 in Aβ1-42-induced neurotoxicity in vitro and in vivo [J]. Neurobiology of Aging, 2014, 35(3): 590-599. DOI:10.1016/j.neurobiolaging.2013.09.036 doi: 10.1016/j.neurobiolaging.2013.09.036

[28]	MEUNIER J , IENI J , MAURICE T . The anti-amnesic and neuroprotective effects of donepezil against amyloid β25-35 peptide-induced toxicity in mice involve an interaction with the σ1 receptor[J]. British Journal of Pharmacology, 2006, 149(8): 998-1012. DOI: 10.1038/sj.bjp.0706927 doi: 10.1038/sj.bjp.0706927

[29]	GUO H B , CHENG Y F , WU J G , et al . Donepezil improves learning and memory deficits in APP/PS1 mice by inhibition of microglial activation[J]. Neuroscience, 2015, 290: 530-542. DOI:10.1016/j.neuroscience.2015.01.058 doi: 10.1016/j.neuroscience.2015.01.058

[30]	CALSOLARO V , EDISON P . Neuroinflammation in Alzheimer’s disease: current evidence and future directions[J]. Alzheimer’s & Dementia, 2016, 12(6): 719-732. DOI:10.1016/j.jalz.2016.02.010 doi: 10.1016/j.jalz.2016.02.010

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