Full Text:   <2678>

Summary:  <1792>

CLC number: R964

On-line Access: 2024-08-27

Received: 2023-10-17

Revision Accepted: 2024-05-08

Crosschecked: 2016-06-18

Cited: 0

Clicked: 3958

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Pan Xu

http://orcid.org/0000-0001-9324-1513

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2016 Vol.17 No.7 P.503-514

http://doi.org/10.1631/jzus.B1500321


Cognitive-enhancing effects of hydrolysate of polygalasaponin in SAMP8 mice


Author(s):  Pan Xu, Shu-ping Xu, Ke-zhu Wang, Cong Lu, Hong-xia Zhang, Rui-le Pan, Chang Qi, Yan-yan Yang, Ying-hui Li, Xin-min Liu

Affiliation(s):  Research Center of Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China; more

Corresponding email(s):   liuxinmin@hotmail.com

Key Words:  Cognitive improvement, Hydrolysate of polygalasaponin, SAMP8 mice


Pan Xu, Shu-ping Xu, Ke-zhu Wang, Cong Lu, Hong-xia Zhang, Rui-le Pan, Chang Qi, Yan-yan Yang, Ying-hui Li, Xin-min Liu. Cognitive-enhancing effects of hydrolysate of polygalasaponin in SAMP8 mice[J]. Journal of Zhejiang University Science B, 2016, 17(7): 503-514.

@article{title="Cognitive-enhancing effects of hydrolysate of polygalasaponin in SAMP8 mice",
author="Pan Xu, Shu-ping Xu, Ke-zhu Wang, Cong Lu, Hong-xia Zhang, Rui-le Pan, Chang Qi, Yan-yan Yang, Ying-hui Li, Xin-min Liu",
journal="Journal of Zhejiang University Science B",
volume="17",
number="7",
pages="503-514",
year="2016",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1500321"
}

%0 Journal Article
%T Cognitive-enhancing effects of hydrolysate of polygalasaponin in SAMP8 mice
%A Pan Xu
%A Shu-ping Xu
%A Ke-zhu Wang
%A Cong Lu
%A Hong-xia Zhang
%A Rui-le Pan
%A Chang Qi
%A Yan-yan Yang
%A Ying-hui Li
%A Xin-min Liu
%J Journal of Zhejiang University SCIENCE B
%V 17
%N 7
%P 503-514
%@ 1673-1581
%D 2016
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1500321

TY - JOUR
T1 - Cognitive-enhancing effects of hydrolysate of polygalasaponin in SAMP8 mice
A1 - Pan Xu
A1 - Shu-ping Xu
A1 - Ke-zhu Wang
A1 - Cong Lu
A1 - Hong-xia Zhang
A1 - Rui-le Pan
A1 - Chang Qi
A1 - Yan-yan Yang
A1 - Ying-hui Li
A1 - Xin-min Liu
J0 - Journal of Zhejiang University Science B
VL - 17
IS - 7
SP - 503
EP - 514
%@ 1673-1581
Y1 - 2016
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1500321


Abstract: 
Objectives: The aim of the study is to evaluate the cognitive-enhancing effects of hydrolysate of polygalasaponin (HPS) on senescence accelerate mouse P8 (SAMP8) mice, an effective Alzheimer’s disease (AD) model, and to research the relevant mechanisms. Methods: The cognitive-enhancing effects of HPS on SAMP8 mice were assessed using Morris water maze (MWM) and step-through passive avoidance tests. Then N-methyl-D-aspartate (NMDA) receptor subunit expression for both the cortex and hippocampus of mice was observed using Western blotting. Results: HPS (25 and 50 mg/kg) improved the escape rate and decreased the escape latency and time spent in the target quadrant for the SAMP8 mice in the MWM after oral administration of HPS for 10 d. Moreover, it decreased error times in the passive avoidance tests. Western blotting showed that HPS was able to reverse the levels of NMDAR1 and NMDAR2B expression in the cortex or hippocampus of model mice. Conclusions: The present study suggested that HPS can improve cognitive deficits in SAMP8 mice, and this mechanism might be associated with NMDA receptor (NMDAR)-related pathways.

远志皂苷水解产物对SAMP8小鼠的益智作用研究

目的:本文主要评价远志皂苷水解产物(HPS)对SAMP8小鼠的益智作用,并对相关机制进行探索。
创新点:HPS相较于远志皂苷有更高的安全性,毒性显著降低或消除;本研究所用的SAMP8模型是一个能较好地同时模拟阿尔兹海默病智力衰退及病理变化的代谢性模型,用于药效评价和机制研究更加可靠。
方法:采用水迷宫(图4和5)及避暗(图6)两种经典的检测方法来评价药物的益智药效,并进一步用免疫印迹实验分析N-甲基-D-天冬氨酸(NMDA)受体水平来对机制进行探索(图7)。
结论:本研究表明,HPS能明显改善SAMP8小鼠的认知损伤,其作用机制与调控NMDA受体相关通路有关。

关键词:认知改善;远志皂苷水解产物;SAMP8小鼠

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Adams, M., Gmunder, F., Hamburger, M., 2007. Plants traditionally used in age related brain disorders—A survey of ethnobotanical literature. J. Ethnopharmacol., 113(3):363-381.

[2]Anand, R., Gill, K.D., Mahdi, A.A., 2014. Therapeutics of Alzheimer’s disease: past, present and future. Neuropsychopharmacology, 76:27-50.

[3]Armbrecht, H.J., Siddiqui, A.M., Green, M., et al., 2014. SAMP8 mice have altered hippocampal gene expression in LTP, phosphatidylinositol signaling, and endocytosis pathways. Neurobiol. Aging, 35(1):159-168.

[4]Bayod, S., Felice, P., Andrés, P., et al., 2015. Downregulation of canonical Wnt signaling in hippocampus of SAMP8 mice. Neurobiol. Aging, 36(2):720-729.

[5]Beal, M.F., 1995. Aging, energy, and oxidative stress in neurodegenerative diseases. Ann. Neurol., 38(3):357-366.

[6]Blennow, K., Leon, M., Zetterberg, H., 2006. Alzheimer’s disease. Lancet, 368(9533):387-403.

[7]Butterfield, D.A., Poon, H.F., 2005. The senescence-accelerated prone mouse (SAMP8): a model of age-related cognitive decline with relevance to alterations of the gene expression and protein abnormalities in Alzheimer’s disease. Exp. Geront., 40(10):774-783.

[8]Cachard-Chastel, M., Devers, S., Sicsic, S., et al., 2008. Prucalopride and donepezil act synergistically to reverse scopolamine-induced memory deficit in C57Bl/6j mice. Behav. Brain Res., 187(2):455-461.

[9]Chung, I., Moore, N., Oh, W., et al., 2002. Behavioural pharmacology of polygalasaponins indicates potential antipsychotic efficacy. Pharmacol. Biochem. Behav., 71(1):191-195.

[10]Dang, H.X., Chen, Y., Liu, X.M., et al., 2009. Antidepressant effects of ginseng total saponins in the forced swimming test and chronic mild stress models of depression. Prog. Neuro-Psychoph., 33(8):1417-1424.

[11]Demetrius, L.A., Driver, J., 2013. Alzheimer’s as a metabolic disease. Biogerontology, 14(6):641-649.

[12]Demetrius, L.A., Magistretti, P.J., Pellerin, L., 2014. Alzheimer’s disease: the amyloid hypothesis and the Inverse Warburg effect. Front. Physiol., 5:522.

[13]Flood, J.F., Morley, J.E., 1998. Learning and memory in the SAMP8 mouse. Neurosci. Biobehav. Rev., 22(1):1-20.

[14]Goverdhan, P., Sravanthi, A., Mamatha, T., 2012. Neuroprotective effects of meloxicam and selegiline in scopolamine-induced cognitive impairment and oxidative stress. Int. J. Alzheimers Dis., 2012:974013.

[15]Grimm, A., Friedland, K., Eckert, A., 2016. Mitochondrial dysfunction: the missing link between aging and sporadic Alzheimer’s disease. Biogerontology, 17(2):281-296.

[16]Hooge, R.D., de Deyn, P.P., 2001. Applications of the Morris water maze in the study of learning and memory. Brain Res. Rev., 36(1):60-90.

[17]Howes, M.J., Houghton, P.J., 2003. Plants used in Chinese and Indian traditional medicine for improvement of memory and cognitive function. Pharmacol. Biochem. Behav., 75(3):513-527.

[18]Huang, Y., Zhang, H., Yang, S., et al., 2012. Liuwei Dihuang decoction facilitates the induction of long-term potentiation (LTP) in senescence accelerated mouse/prone 8 (SAMP8) hippocampal slices by inhibiting voltage-dependent calcium channels (VDCCs) and promoting N-methyl-D-aspartate receptor (NMDA) receptors. J. Ethnopharmacol., 140(2):384-390.

[19]Hynd, M.R., Scott, H.L., Dodd, P.R., 2001. Glutamate (NMDA) receptor NR1 subunit mRNA expression in Alzheimer’s disease. J. Neurochem., 78(1):175-182.

[20]Hynd, M.R., Scott, H.L., Dodd, P.R., 2004. Differential expression of N-methyl-D-aspartate receptor NR2 isoforms in Alzheimer’s disease. J. Neurochem., 90(4):913-919.

[21]Ikeya, Y., Takeda, S., Tunakawa, M., et al., 2004. Cognitive improving and cerebral protective effects of acylated oligosaccharides in Polygala tenuifolia. Biol. Pharm. Bull., 27(7):1081-1085.

[22]Kravitz, E., Gaisler-Salomon, I., Biegon, A., 2013. Hippocampal glutamate NMDA receptor loss tracks progression in Alzheimer’s disease: quantitative autoradiography in postmortem human brain. PLoS ONE, 8(11):e81244.

[23]Kwon, Y.S., Nabeshima, T., Shin, E.J., 2004. PAP 9704, a Korean herbal medicine attenuates methamphetamine-induced hyperlocomotion via adenosine A2A receptor stimulation in mice. Biol. Pharm. Bull., 27(6):906-909.

[24]Lacaille-Dubois, M.A., Mitaine-Offer, A.C., 2005. Triterpene saponins from Polygalaceae. Phytochem. Rev., 4(2-3):139-149.

[25]Li, Z.Y., Liu, Y.M., Wang, L.W., et al., 2014. Memory-enhancing effects of the crude extract of Polygala tenuifolia on aged mice. eCAM, 2014:392324.

[26]Lin, Z.H., Gu, J., Xiu, J., et al., 2012. Traditional Chinese medicine for senile dementia. eCAM, 2012:692621.

[27]López-Ramos, J.C., Jurado-Parras, M.T., Sanfeliu, C., et al., 2012. Learning capabilities and CA1-prefrontal synaptic plasticity in a mice model of accelerated senescence. Neurobiol. Aging, 33(3):613-626.

[28]Ma, B., Li, X., Li, J., et al., 2014. Quantitative analysis of tenuifolin concentrations in rat plasma and tissue using LCMS/MS: application to pharmacokinetic and tissue distribution study. J. Pharm. Biomed. Anal., 88(25):191-200.

[29]Mishizen-Eberz, A.J., Rissman, R.A., Carter, T.L., et al., 2004. Biochemical and molecular studies of NMDA receptor subunits NR1/2A/2B in hippocampal subregions throughout progression of Alzheimer’s disease pathology. Neurobiol. Dis., 15(1):80-92.

[30]Misra, S., Medhi, B., 2013. Drug development status for Alzheimer’s disease: present scenario. Neurol. Sci., 34(6):831-839.

[31]Morley, J.E., Farr, S.A., Kumar, V.B., et al., 2012. The SAMP8 mouse: a model to develop therapeutic interventions for Alzheimer’s disease. Curr. Pharm. Des., 18(8):1123-1130.

[32]Morris, R., 1984. Developments of a water-maze procedure for studying spatial learning in the rat. J. Neurosci. Method., 11(1):47-60.

[33]Parameshwaran, K., Dhanasekaran, M., Suppiramaniam, V., 2008. Amyloid beta peptides and glutamatergic synaptic dysregulation. Exp. Neurol., 210(1):7-13.

[34]Pike, C.J., Rosario, E.R., Nguyen, T.V., 2006. Androgens, aging, and Alzheimer’s disease. Endocrine, 29(2):233-241.

[35]Rebola, N., Srikumar, B.N., Mulle, C., 2010. Activity-dependent synaptic plasticity of NMDA receptors. J. Physiol., 588(1):93-99.

[36]Reitz, C., Brayne, C., Mayeux, R., 2011. Epidemiology of Alzheimer disease. Nat. Rev. Neurol., 7(3):137-152.

[37]Rupsingh, R., Borrie, M., Smith, M., et al., 2011. Reduced hippocampal glutamate in Alzheimer disease. Neurobiol. Aging, 32(5):802-810.

[38]Senechal, Y., Kelly, P.H., Dev, K.K., 2008. Amyloid precursor protein knockout mice show age-dependent deficits in passive avoidance learning. Behav. Brain Res., 186(1):126-132.

[39]Shi, C., Xiao, S., Liu, J., et al., 2010. Ginkgo biloba extract EGb761 protects against aging-associated mitochondrial dysfunction in platelets and hippocampi of SAMP8 mice. Platelets, 21(5):373-379.

[40]Strong, R., Reddy, V., Morley, J.E., 2003. Cholinergic deficits in the septal-hippocampal pathway of the SAM-P/8 senescence accelerated mouse. Brain Res., 966(1):150-156.

[41]Sun, F., Sun, J.D., Han, N., et al., 2012. Polygalasaponin F induces long-term potentiation in adult rat hippocampus via NMDA receptor activation. Acta Pharmacol. Sin., 33(4):431-437.

[42]Takeda, T., 2009. Senescence-accelerated mouse (SAM) with special references to neurodegeneration models, SAMP8 and SAMP10 mice. Neurochem. Res., 34(4):639-659.

[43]Takemura, M., Nakamura, S., Akiguchi, I., et al., 1993. β/A4 proteinlike immunoreactive granular structures in the brain of senescenceaccelerated mouse. Am. J. Surg. Pathol., 142(6):1887-1897.

[44]Wang, Q., Sun, L.H., Jia, W., et al., 2010. Comparison of ginsenosides Rg1 and Rb1 for their effects on improving scopolamineinduced learning and memory impairment in mice. Phytoth. Res., 24(12):1748-1754.

[45]Wang, Q., Xiao, B.X., Pan, R.L., et al., 2015. An LC-MS/MS method for simultaneous determination of three Polygala saponin hydrolysates in rat plasma and its application to a pharmacokinetic study. J. Ethnopharmacol., 169(1):401-406.

[46]Webster, S.J., Bachstetter, A.D., Nelson, P.T., et al., 2014. Using mice to model Alzheimer’s dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models. Front. Genet., 5(88):1-23.

[47]Wu, M.M., Yuan, Y.H., Chen, J., et al., 2014. Polygalasaponin F against rotenone-induced apoptosis in PC12 cells via mitochondria protection pathway. J. Asian Nat. Prod. Res., 16(1):59-69.

[48]Xu, J., Shi, C., Li, Q., et al., 2007. Mitochondrial dysfunction in platelets and hippocampi of senescence-accelerated mice. J. Bioenerg. Biomembr., 39(2):195-202.

[49]Xu, S.P., Yang, Y.Y., Xue, D., et al., 2011. Cognitive-enhancing effects of polygalasaponin hydrolysate in Aβ25−35-induced amnesic mice. eCAM, 2011:839720.

[50]Xu, X.H., Zhou, J.F., Li, T.Z., et al., 2009. Polygalasaponin G promotes neurite outgrowth of cultured neuron on myelin. Neurosci. Lett., 460(1):41-46.

[51]Xue, W., Hu, J.F., Yuan, Y.H., et al., 2009. Polygalasaponin XXXII from Polygala tenuifolia root improves hippocampal-dependent learning and memory. Acta Pharmacol. Sin., 30(9):1211-1219.

[52]Yang, S., Qiao, H., Wen, L., et al., 2005. D-Serine enhances impaired long-term potentiation in CA1 subfield of hippocampal slices from aged senescence-accelerated mouse prone/8. Neurosci. Lett., 379(1):7-12.

[53]Yashiro, K., Philpot, B.D., 2008. Regulation of NMDA receptor subunit expression and its implications for LTD, LTP, and metaplasticity. Neuropharmacology, 55(7):1081-1094.

[54]Zadori, D., Veres, G., Szalardy, L., et al., 2014. Glutamatergic dysfunctioning in Alzheimer’s disease and related therapeutic targets. J. Alzheimers Dis., 42(3):177-187.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE