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01-12-2016 | Original Article

Timosaponin B-II ameliorates scopolamine-induced cognition deficits by attenuating acetylcholinesterase activity and brain oxidative damage in mice

Authors: Xu Zhao, Chunmei Liu, Yu Qi, Lina Fang, Jie Luo, Kaishun Bi, Ying Jia

Published in: Metabolic Brain Disease | Issue 6/2016

Abstract

Timosaponin B-II (TB-II) is a main active saponin isolated from the rhizome of Anemarrhena asphodeloides Bge., which is widely used in traditional Chinese medicine. In this study, the effect of TB-II on learning and memory was investigated in a scopolamine-induced mouse model of Alzheimer’s disease. The results of behavioral tests indicated that TB-II significantly increased the spontaneous alternation in the Y-maze test, and reversed the shortening of step-through latency induced by scopolamine in the passive avoidance test, showing protective effects on short-term and working memory. In the Morris water maze test, TB-II reduced the escape latency time in the training trial, and increased the swimming time in the target quadrant in the probe trial. Biochemical data demonstrated that TB-II significantly inhibited acetylcholinesterase (AChE) activity in the cerebral cortex and hippocampus of mice. Moreover, TB-II markably attenuated the reduction in glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities, and decreased malondialdehyde (MDA) levels, which are key biomarkers of brain oxidative stress. These results indicated that TB-II offers protection against scopolamine-induced deficits in learning and memory, possibly by inhibiting AChE and preventing oxidative stress damage. The findings suggested that TB-II has a potential therapeutic effect on cognitive and behavioral impairment.

Abbatecola AM, Olivieri F, Corsonello A, Antonicelli R, Corica F (2011) Genome-wide association studies: is there a genotype for cognitive decline in older persons with type 2 diabetes? Curr Pharm Design 4:347–356CrossRef

Ahmed T, Gilani AH (2009) Inhibitory effect of curcuminoids on acetylcholinesterase activity and attenuation of scopolamine-induced amnesia may explain medicinal use of turmeric in Alzheimer’s disease. Pharmacol Biochem Be 91:554–559CrossRef

Araujo AJ, Studzinski CM, Milgram NW (2005) Further evidence for the cholinergic hypothesis of aging and dementia from the canine model of aging. Prog Neuro-Psychoph 29:411–422CrossRef

Banks WA (2012) Drug delivery to the brain in the Alzheimer’s disease: Consideration of the blood–brain barrier. Adv Drug Deliv Rev 64:629–639CrossRefPubMed

Brandon E, Mellott T, Pizzo D, Coufal N, D’Amour K, Gobeske K, Lortie M, Lopez-Coviella I, Berse B, Thal L, Gage F, Blusztajn J (2004) Choline transporter 1 maintains cholinergic function in cholineacetyl transfer as ehaploin sufficiency. J Neurosci 24:5459–5466CrossRefPubMed

Cobb CA, Cole MP (2015) Oxidative and nitrative stress in neurodegeneration. Neurobiol Dis 84:4–21CrossRefPubMedPubMedCentral

Deng XY, Chen JJ, Li HY, Ma ZQ, Ma SP, Fu Q (2015) Cardioprotective effects of timosaponin B II from Anemarrhenae asphodeloides Bge. on isoproterenol-induced myocardial infarction in rats. Chem Biol Interact 240:22–28CrossRefPubMed

Droogsma E, Veeger N, vanWalderveen P, Niemarkt S, vanAsselt D (2013) Effect of treatment gaps in elderly patients with dementia treated with cholinesterase inhibitors. Proc Natl Acad Sci U S A 80:1622

Gao X, Zheng CY, Yang L, Tang XC, Zhang HY (2009) Huperzine A protects isolated rat brain mitochondria against β-amyloid peptide,. Free Radic Biol Med 46:1454–1462CrossRefPubMed

Guo CR, Shen JY, Meng ZQ, Yang XL, Li F (2016) Neuroprotective effects of polygalacic acid on scopolamine-induced memory deficitsin mice, Phytomedicine 23: 149–155

Gupta VK, Chitranshi N, Gupta VB, Golzan M, Dheer Y, Wall RV, Georgevsky D, King AE, Vickers JC, Chung R, Graham S (2016) Amyloid β accumulation and inner retinal degenerative changes in Alzheimer’s disease transgenic mouse. Neurosci Lett 623:51–56CrossRef

He DD, Wu H, Wei Y, Liu W, Huang F, Shi HL, Zhang BB, Wu XJ, Wang CH (2015) Effects of harmine, an acetylcholinesterase inhibitor, on spatial learning and memory of APP/PS1 transgenic mice and scopolamine-induced memory impairment mice, European Journal of Pharmacology 768: 96–107

Huang JF, Shang L, Liu P, Zhang MQ, Chen S, Chen D, Fan CL, Wang H, Xiong K (2012) Timosaponin-BII inhibits the up-regulation of BACE1 induced by Ferric Chloride in rat retina. BMC Complement Altern Med 12:1–8

Iida Y, KB O, Saito M, Matsuoka H, Kurata H, Natsume M, Abe H (1999) Detection of antifungal activity in Anemarrhenaasphodeloides by sensitive BCT method and isolation of itsactive compound. J Agric Food Chem 47:584–587CrossRefPubMed

Iversen S (1997) Behavioural evaluation of cholinergic drugs. Life Sci 60:1145–1152CrossRefPubMed

Jiang SH, Shang L, Xue LX, Ding W, Chen S, Ma RF, Huang JF, Xiong K (2014) The effect and underlying mechanism of Timosaponin B-II on RGC-5 necroptosis induced by hydrogen peroxide. BMC Complement Altern Med 14:1472–6882

Jollow DJ, Mitchell JR, Zampaglione N, Gillette JR (1974) Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3, 4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology 3:151–169CrossRef

Kim DH, Hung TM, Bae KH (2007) The ameliorating effect of oroxylin A on scopolamine-induced memory impairment in mice. Neurobiol Learn Mem 87:536–546CrossRefPubMed

Lan Z, Liu J, Chen LFQ, Luo J, Qu R, Kong L, Ma S (2012) Danggui-Shaoyao-San ameliorates cognition deficits and attenuates oxidative stress-related neuronal apoptosis in D-galactose-induced senescent mice. J Ethnopharmacol 141:386–395CrossRefPubMed

Lee JS, Kim HG, Han JM, Kim DW, Yi MH, Son SW, Kim YA, Lee JS, Choi MK, Son CG (2014) Ethanol extract of Astragali Radix and Salviae Miltiorrhizae Radix, Myelophil, Exerts anti-amnesic effect in a mouse model of scopolamine-induced memory deficits. J Ethnopharmacol 153:782–789CrossRefPubMed

Li TJ, Qiu Y, Yang PY, Rui YC, Chen WS (2007) Timosaponin B-II improves memory and learning dysfunction induced by cerebral ischemia in rats. Neurosci Lett 421:147–151CrossRefPubMed

Liu J, Deng W, Fan L, Tian L, Jin L, Jin Z, Guo Q, Xu Y, Li N (2012a) The role of radix hedysari polysaccharide on thehuman umbilical vein endothelial cells induced by highglucose. Eur J Intern Med 23:287–292CrossRefPubMed

Liu Y, Zhu X, Lu Q, Wang J, Li W, Wei Y, Yin X (2012b) Totalsaponins from Rhizoma Anemarrhenae amelioratediabetes-associated cognitive decline in rats: involvement ofamyloid-beta decrease in brain. J Ethnopharmacol 139:194–200CrossRefPubMed

Lu W, Qiu Y, Li TJ, Tao X, Sun LN, Chen WS (2009) Timosaponin B-II inhibits proinflammatory cytokineinduction by lipopolysaccharide in BV2 cells. Arch Pharm Res 32:1301–1308CrossRefPubMed

Lynch T, Cherny RA, Bush AI (2000) Oxidative processes in Alzheimer’s disease: the role of Aβ-metal interactions. Exp Gerontol 35:445–451CrossRefPubMed

Ma T, Gong K, Yan YF, Zhang LH, Tang PF, Zhang XF, Gong YD (2013) Huperzine A promotes hippocampal neurogenesis in vitro and in vivo. Brain Res 1506:35–43CrossRefPubMed

Moreira PI, Sayre LM, Zhu X, Nunomura A, Smith MA, Perry G (2010) Detection and localization of markers of oxidative stress by in situ methods: application in the study of Alzheimer disease. Methods Mol Biol 610:419–434CrossRefPubMed

Morris R (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11:47–60CrossRefPubMed

Radomska-Leśniewska DM, Hevelke A, Skopiński P, Barbara B, Józwiak J, Rokicki D, Skopińska-Różewska E, Białoszewska A (2016) Reactive oxygen species and synthetic antioxidants as angiogenesis modulators: Clinical implications. Pharmacol Rep 68:462–471CrossRefPubMed

Rijpma A, Meulenbroek O, Olde R (2014) Cholinesterase inhibitors and add-on nutritional supplements in Alzheimer’s disease: a systematic review of randomized controlled trials. Ageing Res Rev 16:105–112CrossRefPubMed

Rodda J, Carter J (2012) Cholinesterase inhibitors and memantine for symptomatic treatment of dementia. BMJ 344: 537–538

Roghani M, Baluchnejadmojarad T (2009) Chronic epigallocatechin-gallate improves aortic reactivity of diabetic rats: Underlying mechanisms. Vasc Pharmacol 51:84–89CrossRef

Shen Z (2004) Brain cholinesterases: II. The molecular and cellular basis of Alzheimer’s disease. Med Hypotheses 63:308–321CrossRefPubMed

Shi J, Liu QF, Wang YM, Luo GA (2010) Coadministration of huperzine A and ligustrazine phosphate effectively reverses scopolamine-induced amnesia in rats. Pharmacol Biochem Be 96:449–453CrossRef

Slater TF (1984) Overview of methods used for detecting lipid peroxidation. Methods Enzymol 105:283–293CrossRefPubMed

Terry JA, Callahan PM, Hall B, Webster SJ (2011) Alzheimer’s disease and age-relate memory decline (preclinical). Pharmacol Biochem Be 99:190–210CrossRef

Xie W, Du L (2011) Diabetes is an inflammatory disease:evidence from traditional Chinese medicines. Diabetes Obes Metab 13:289–301CrossRefPubMed

Zhang HY, Tang XC (2006) Neuroprotective effects of huperzine A: new therapeutic targets for neurodegenerative disease. Trends Pharmacol Sci 27:619–625CrossRefPubMed

Zhang J, Zhang M (1999) Effect of steroidal saponins of Anemarrhenae rhizoma on superoxide generation in human neutrophils. Biocheml Bioph Res Co 259:636–639CrossRef

Title: Timosaponin B-II ameliorates scopolamine-induced cognition deficits by attenuating acetylcholinesterase activity and brain oxidative damage in mice
Authors: Xu Zhao
Chunmei Liu
Yu Qi
Lina Fang
Jie Luo
Kaishun Bi
Ying Jia
Publication date: 01-12-2016
Publisher: Springer US
Published in: Metabolic Brain Disease / Issue 6/2016
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-016-9877-z

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Timosaponin B-II ameliorates scopolamine-induced cognition deficits by attenuating acetylcholinesterase activity and brain oxidative damage in mice

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

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