Search JIM Advanced Search

Journal of Chinese Integrative Medicine ›› 2010, Vol. 8 ›› Issue (10): 955-960.doi: 10.3736/jcim20101007

• Original Experimental Research • Previous Articles     Next Articles

Effects of gensenoside Rg1 on tau protein phosphorylation induced by okadaic acid in rat brain slices

Xi Lia, Ying Liua, Hai-feng Yuanb, Qian-kun Quanc   

  1. a Department of Geriatrics, the Second Affiliated Hospital, Xi’an Jiaotong University College of Medicine,Xi’an 710004, Shaanxi Province, China;
    b Department of Neurology, the Second Affiliated Hospital, Xi5an Jiaotong University College of Medicine, Xi5 an 710004, Shaanxi Province, China
    c Research Center of Rehabilitation Science and Technology, School of Life Science and Technology, Xi5an Jiaotong University, Xi’an 710049,Shaanxi Province,China;
  • Received:2010-03-26 Accepted:2010-05-27 Online:2010-10-20 Published:2010-10-15

Objective

To investigate the effects of gensenoside Rg1 on expressions of phosphorylated tau protein (P-tau), protein phosphatase 2A (PP2A) and tau protein in Alzheimer’s disease-like tau phosphorylation rat brain slices, and to explore the mechanisms of gensenoside Rg1 in inhibiting tau phosphorylation.
Methods

Brains of 5-week-old Wistar rats were cut into slices which were 400 μm thick. These brain slices were randomly divided into blank control group, untreated group, low-dose ginsenoside Rg1 group, medium-dose ginsenoside Rg1 group and high-dose ginsenoside Rg1 group, with 10 slices in each group. All brain slices were cultured with artificial cerebrospinal fluid (ACSF). And brain slices in the ginsenoside R1 groups were administered with ginsenoside Rg1 (60, 120 and 240 μmol/L respectively) in ACSF for 2 h firstly. After 2-hour culture, okadaic acid (OA) was administered into ACSF of the untreated group and the ginsenoside Rg1 groups separately for 3 h to induce tau phosphorylation to prepare AD models. The concentration of OA in each group was 1 μmol/L. There was no any intervention for the brain slices in the blank control group. Expressions of P-tau, PP2A and tau proteins in the brain slices were determined by immunohistochemical method, and the results were analyzed by image acquisition and analysis system.
Results

Compared with the blank control group, the expression of P-tau protein was significantly increased (P<0.01) and the expressions of tau and PP2A proteins were decreased (P<0.01, P<0.05) in the untreated group. Compared with the untreated group, the expression of P-tau was significantly decreased (P<0.01) and the expressions of tau and PP2A proteins were increased (P<0.01, P<0.05) in the ginsenoside Rg1 groups, especially in the high-dose ginsenoside Rg1 group.
Conclusion

Ginsenoside Rg1 can promote dephosphorylation of P-tau by increasing the expression of PP2A in Alzheimer’s disease-like tau phosphorylation rat brain slices, so as to inhibit tau phosphorylation.

Key words: Gensenoside Rgl, Alzheimer's disease, Phosphorylated tau protein, Protein phosphatase 2A, Tau protein, Rats

Table 1

Expression of P-tau protein in rat brain slices in different groups"

Figure 1

Expression of P-tau protein in dentate gyrus of hippocampus in different groups observed by immunohistochemical method (Light microscopy, ×400) A: Blank control group; B: Untreated group; C: High-dose ginsenoside Rg1 group."

Table 2

Expression of PP2A protein in rat brain slices in different groups"

Figure 2

Expression of PP2A protein in cortex in different groups observed by immunohistochemical method (Light microscopy, ×400) A: Blank control group; B: Unrelated group; C: High-dose ginsenoside Rg1 group."

Table 3

Expression of tau protein in rat brain slices in different groups"

Figure 3

Expression of tau protein in area CA1 of hippocampus in different groups observed by immunohistochemical method (Light microscopy, ×400) A: Blank control group; B: Untreated group; C: High-dose ginsenoside Rg1 group."

[1] Liu YH, Wang JZ . Relationship between abnormal tau protein expression and Alzheimer’s disease[J]. Sheng Ming De Hua Xue, 2006,26(2):108-110
doi: 10.3969/j.issn.1000-1336.2006.02.005
刘英华, 王建枝 . tau蛋白异常与阿尔茨海默病的关系[J]. 生命的化学, 2006,26(2):108-110
doi: 10.3969/j.issn.1000-1336.2006.02.005
[2] Arriagada PV, Growdon JH, Hedley-Whyte ET, Hyman BT . Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer’s disease[J]. Neurology, 1992,42(3 Pt 1):631-639
doi: 10.1212/WNL.42.3.631
[3] Giannakopoulos P, Herrmann FR, Bussière T, Bouras C, Kövari E, Perl DP, Morrison JH, Gold G, Hof PR .Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer’s disease[J]. Neurology, 2003,60(9):1495-1500
doi: 10.1212/01.WNL.0000063311.58879.01
[4] Zhang JT . Nootropic mechanisms of ginsenoside Rg1 — influence on neuronal plasticity and neurogenesis[J]. Yao Xue Xue Bao, 2005,40(5):385-388
doi: 10.3321/j.issn:0513-4870.2005.05.001
张均田 . 人参皂苷Rg1的促智作用机制——对神经可塑性和神经发生的影响[J]. 药学学报, 2005,40(5):385-388
doi: 10.3321/j.issn:0513-4870.2005.05.001
[5] Gong CX, Lidsky T, Wegiel J, Grundke-Iqbal I, Iqbal K . Metabolically active rat brain slices as a model to study the regulation of protein phosphorylation in mammalian brain[J]. Brain Res Protoc, 2001,6(3):134-140
doi: 10.1016/S1385-299X(00)00046-5
[6] Ma YX, Yu ZW. Modern dementia studie[M]. Beijing: Scientific and Technological Literature Publishing House,2008: 786
马永兴, 俞卓伟 . 现代痴呆学[M]. 北京: 科学技术文献出版社,2008: 786
[7] Sheng SL. Alzheimer’s disease: from molecular biology to clinical diagnosis and treatment[M]. Beijing: Scientific and Technological Literature Publishing House,1998: 207-208
盛树力 . 老年性痴呆: 从分子生物学到临床诊治[M]. 北京: 科学技术文献出版社,1998: 207-208
[8] Gong CX, Wegiel J, Lidsky T, Zuck L, Avila J, Wisniewski HM, Grundke-Iqbal I, Iqbal K . Regulation of phosphorylation of neuronal microtubule-associated proteins MAP1b and MAP2 by protein phosphatase-2A and -2B in rat brain[J]. Brain Res, 2000,853(2):299-309
doi: 10.1016/S0006-8993(99)02294-5
[9] Wei Q, Yu DY, Wu HZ . Alzheimer’s disease and phosphorylation and dephosphorylation of tau protein[J]. Zhongguo Hang Tian Yi Yao Za Zhi, 2004,6(2):1-5
魏群, 于大禹, 吴和珍 . 阿尔茨海默病与tau蛋白的磷酸化及去磷酸化[J]. 中国航天医药杂志, 2004,6(2):1-5
[10] Vogelsberg-Ragaglia V, Schuck T, Trojanowski JQ, Lee VM . PP2A mRNA expression is quantitatively decreased in Alzheimer’s disease hippocampus[J]. Exp Neurol, 2001,168(2):402-412
doi: 10.1006/exnr.2001.7630
[11] Schild A, Ittner LM, Götz J .Altered phosphorylation of cytoskeletal proteins in mutant protein phosphatase 2A transgenic mice[J]. Biochem Biophys Res Commun, 2006,343(4):1171-1178
doi: 10.1016/j.bbrc.2006.03.066
[12] Cohen P, Holmes CF, Tsukitani Y . Okadaic acid: a new probe for the study of cellular regulation[J]. Trends Biochem Sci, 1990,15(3):98-102
doi: 10.1016/0968-0004(90)90192-E pmid: 2158158
[13] Tian Q, Zhang Q, Wang Q, Wang JZ . Hyperphosphorylation of tau and decrease of Ach level in the Meynert nucleus basalis of rat brain induced by OA[J]. Hua Zhong Ke Ji Da Xue Xue Bao Zi Ran Ke Xue Ban, 2004,32(12):94-96
doi: 10.3321/j.issn:1671-4512.2004.12.033
田青, 张蕲, 王群, 王建枝 . OA诱导大鼠基底核Ach降低及τ蛋白过度磷酸化[J]. 华中科技大学学报(自然科学版), 2004,32(12):94-96
doi: 10.3321/j.issn:1671-4512.2004.12.033
[14] Peng XS, Cheng XC, Huang JS, Zhu YG, Li YK . The effect of ginsenoside Rg1 on abnormal phosphorylation of tau in rat’s hippocampal neurons induced by aggregated Aβ25-35[J]. Zhongguo Yao Li Xue Tong Bao, 2005,21(3):299-305
彭小松, 陈晓春, 黄俊山, 朱元贵, 李永坤 . 人参皂苷Rg1对Aβ25-35诱导大鼠海马神经元tau蛋白异常磷酸化的影响[J]. 中国药理学通报, 2005,21(3):299-305
[15] Zhang J, Huang TW, Chen XC, Song JQ, Zeng YQ . Ginsenoside Rg1 attenuates tau hyperphosporylation induced by fibrillar Aβ25-35 in primary cortical neurons through cyclin-dependent kinase 5 signaling[J]. Fujian Yi Ke Da Xue Xue Bao, 2008,42(1):9-11
张静, 黄天文, 陈晓春, 宋锦秋, 曾育琦 . 人参皂苷Rg1通过CDK5途径减轻Aβ25-35诱导的神经元tau蛋白磷酸化[J]. 福建医科大学学报, 2008,42(1):9-11
[16] Li X, Zhang X, Zhang ZY, Yuan HF, Quan QK . The effects of gensenoside Rg1 on the expressions of P-Tau and PKA on the brain slices of AD model rats[J]. Zhongguo Lao Nian Xue Za Zhi, 2009,29(19):2468-2470
doi: 10.3969/j.issn.1005-9202.2009.19.021
李玺, 张欣, 张智燕, 袁海峰, 权乾坤 . 人参皂苷Rg1对AD模型大鼠脑片P-Tau、PKA影响的实验研究[J]. 中国老年学杂志, 2009,29(19):2468-2470
doi: 10.3969/j.issn.1005-9202.2009.19.021
[17] Zeng YQ, Chen XC, Huang C, Li YK, Peng XS, Shen J, Huang TW . The attenuation of β-amyloid peptide 25-35-induced tau hyperhosporylation in cortical neurons by the regulation of ginsenoside Rg1 on the activity of GSK-3β and PP2A[J]. Jie Pou Xue Bao, 2007,38(6):665-670
doi: 10.3321/j.issn:0529-1356.2007.06.008
曾育琦, 陈晓春, 黄春, 李永坤, 彭小松, 沈杰, 黄天文 . 人参皂苷Rg1通过调节GSK-3β/PP2A 活性减轻皮层神经元Tau蛋白过度磷酸化[J]. 解剖学报, 2007,38(6):665-670
doi: 10.3321/j.issn:0529-1356.2007.06.008
[1] Morufu Eyitayo Balogun, Elizabeth Enohnyaket Besong, Jacinta Nkechi Obimma, Ogochukwu Sophia Mbamalu, Fankou Serges Athanase Djobissie. Protective roles of Vigna subterranea (Bambara nut) in rats with aspirin-induced gastric mucosal injury. Journal of Integrative Medicine, 2018, 16(5): 342-349.
[2] Lucky Legbosi Nwidu, Raphael Ellis Teme. Hot aqueous leaf extract of Lasianthera africana (Icacinaceae) attenuates rifampicin-isoniazid-induced hepatotoxicity. Journal of Integrative Medicine, 2018, 16(4): 263-272.
[3] Kylie Connolly, Douglas Jackson, Candice Pullen, Andrew Fenning. Alpha-adrenoceptor antagonism by Crassostrea gigas oyster extract inhibits noradrenaline-induced vascular contraction in Wistar rats. Journal of Integrative Medicine, 2015, 13(3): 194-200.
[4] Hussein O. B. Oloyede, Matthew C. Adaja, Taofeek O. Ajiboye, Musa O. Salawu. Anti-ulcerogenic activity of aqueous extract of Carica papaya seed on indomethacin-induced peptic ulcer in male albino rats. Journal of Integrative Medicine, 2015, 13(2): 105-114.
[5] Udhaya Lavinya Baskaran, Sherry Joseph Martin, Rasool Mahaboobkhan, Sabina Evan Prince. Protective role of Triphala, an Indian traditional herbal formulation, against the nephrotoxic effects of bromobenzene in Wistar albino rats. Journal of Integrative Medicine, 2015, 13(2): 115-121.
[6] Anirudha A. Lande, Shirishkumar D. Ambavade, Uma S. Swami, Prafulla P. Adkara Prashant D. Ambavade, Arun B. Waghamare. Saponins isolated from roots of Chlorophytum borivilianum reduce acute and chronic inflammation and histone deacetylase. Journal of Integrative Medicine, 2015, 13(1): 25-33.
[7] Elizabeth Abidemi Balogun, Sylvia Orume Malomo, Joseph Oluwatope Adebayo, Ahmed Adebayo Ishola, Ayodele Olufemi Soladoye, Lawrence Aderemi Olatunji, Olatunji Matthew Kolawole, Stephen Olubunmi Oguntoye, Abiola Samuel Babatunde, Oluwole Busayo Akinola . In vivo antimalarial activity and toxicological effects of methanolic extract of Cocos nucifera (Dwarf red variety) husk fibre. Journal of Integrative Medicine, 2014, 12(6): 504-511.
[8] Xin-fang Zhang, Ji Zhu, Wen-ye Geng, Shu-jun Zhao, Chuan-wei Jiang, Sheng-rong Cai, Miao Cheng, Chuan-yun Zhou, Zi-bing Liu. Electroacupuncture at Feishu (BL13) and Zusanli (ST36) down-regulates the expression of orexins and their receptors in rats with chronic obstructive pulmonary disease. Journal of Integrative Medicine, 2014, 12(5): 417-424.
[9] Urmila Aswar, Mayuri Gurav, Ganesh More, Khaled Rashed, Manoj Aswar. Effect of aqueous extract of Solanum xanthocarpum Schrad. & Wendl. on postmenopausal syndrome in ovariectomized rats. Journal of Integrative Medicine, 2014, 12(5): 439-446.
[10] Benjamin Perry, Junzeng Zhang, Tarek Saleh, Yanwen Wang. Liuwei Dihuang, a traditional Chinese herbal formula, suppresses chronic inflammation and oxidative stress in obese rats. Journal of Integrative Medicine, 2014, 12(5): 447-454.
[11] Upendarrao Golla, Praveen Kumar Gajam, Solomon Sunder Bhimathati. Evaluation of diuretic and laxative activity of hydro-alcoholic extract of Desmostachya bipinnata (L.) Stapf in rats. Journal of Integrative Medicine, 2014, 12(4): 372-378.
[12] Qian Zhang, Xin-hua Xiao, Ming Li, Wen-hui Li, Miao Yu, Hua-bing Zhang, Fan Ping, Zhi-xin Wang, Jia Zheng ​. Chromium-containing traditional Chinese medicine, Tianmai Xiaoke Tablet improves blood glucose through activating insulin-signaling pathway and inhibiting PTP1B and PCK2 in diabetic rats. Journal of Integrative Medicine, 2014, 12(3): 162-170.
[13] Amir Rashidian​, Saeed Mehrzadi, Ali Reza Ghannadi, Parvin Mahzooni, Samira Sadr, Mohsen Minaiyan​. Protective effect of ginger volatile oil against acetic acid-induced colitis in rats: A light microscopic evaluation. Journal of Integrative Medicine, 2014, 12(2): 115-120.
[14] Dilpesh Jain​, Manish Kumar Bansal, Rahul Dalvi​, Aman Upganlawar​, Rahul Somani​. Protective effect of diosmin against diabetic neuropathy in experimental rats. Journal of Integrative Medicine, 2014, 12(1): 35-41.
[15] Manjusha Choudhary​, Vipin Kumar​, Surender Singh​. Gastric antisecretory and cytoprotective effects of hydroalcoholic extracts of Plumeria alba Linn. leaves in rats. Journal of Integrative Medicine, 2014, 12(1): 42-51.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] Jin-zhou Tian, Jing Shi, Xin-qing Zhang, Qi Bi, Xin Ma, Zhi-liang Wang, Xiao-bin Li, Shu-li Shen, Lin Li, Zhen-yun Wu, Li-yan Fang, Xiao-dong Zhao, Ying-chun Miao, Peng-wen Wang, Ying Ren, Jun-xiang Yin, Yong-yan Wang, Beijing United Study Group on MCI of the Capital Foundation of Medical Developments. An explanation on "guiding principles of clinical research on mild cognitive impairment (protocol)". Journal of Chinese Integrative Medicine, 2008, 6(1): 15-21
[2] Jun Cai, Hua Wang, Sheng Zhou, Bin Wu, Hua-rong Song, Zheng-rong Xuan. Effect of Sijunzi Decoction and enteral nutrition on T-cell subsets and nutritional status in patients with gastric cancer after operation: A randomized controlled trial. Journal of Chinese Integrative Medicine, 2008, 6(1): 37-40
[3] Dong Yang, Yong-ping Du, Qing Shen, Wei Chen, Yan Yu, Guang-lei Chen. Expression of alpha-smooth muscle actin in renal tubulointerstitium in patients with kidney collateral stasis. Journal of Chinese Integrative Medicine, 2008, 6(1): 41-44
[4] SUN Ming-yu, ZUO Jian, DUAN Ji-feng, HAN Jun, FAN Shi-ming, ZHANG Wei, ZHU Li-fang, YAO Ming-hui. Antitumor activities of kushen flavonoids in vivo and in vitro. Journal of Chinese Integrative Medicine, 2008, 6(1): 51-59
[5] Hai-feng Wei, Bai-liu Ya, Ling Zhao, Cui-fei Ye, Li Zhang, Lin Li. Evaluation of tongue manifestation of blood stasis syndrome and its relationship with blood rheological disorder in a rat model of transient brain ischemia. Journal of Chinese Integrative Medicine, 2008, 6(1): 73-76
[6] Guo-hong Yuan, Xiao-jing Pang, He-chao Ma. Synergic effects of Danggui Buxue Decoction in reducing toxicity of cytoxan in tumor-bearing mice. Journal of Chinese Integrative Medicine, 2008, 6(1): 83-88
[7] Bo Wang , Wei Yan , Li-hui Hou, Xiao-ke Wu. Disorder of Tiangui (kidney essence) and reproductive dysfunction in patients with polycystic ovary syndrome. Journal of Chinese Integrative Medicine, 2010, 8(11): 1018-1022
[8] Wei Xu, Meng Shi, Jian-gang Liu, Cheng-long Wang . Collagen protein expressions in ischemic myocardium of rats with acute myocardial infarction and effects of qi-tonifying, yin-tonifying and blood-activating herbs and detoxifying and blood-activating herbs. Journal of Chinese Integrative Medicine, 2010, 8(11): 1041-1047
[9] Bing Hu , Hong-mei An , Ke-ping Shen , Qin Du. Senescence-inducing effects of Chinese herbal medicine Tenglong Buzhong Decoction on human colon carcinoma LS-174-T cells and the mechanism. Journal of Chinese Integrative Medicine, 2010, 8(11): 1048-1052
[10] Ya-hui Liang , Ping Li, Jing-xia Zhao, Xin Liu, Qi-fu Huang. Acetyl-11-keto-beta-boswellic acid and arsenic trioxide regulate the productions and activities of matrix metalloproteinases in human skin fibroblasts and human leukemia cell line THP-1. Journal of Chinese Integrative Medicine, 2010, 8(11): 1060-1069