Neuroprotective Effects of an Aqueous Extract of Futokadsura Stem in an Aβ-Induced Alzheimer's Disease-Like Rat Model

10.4077/CJP.2015.BAD273

Wen Xia；Da-Wei Li；Lan Xiang；Jun-Jing Chang；Zuo-Li Xia；En-Ji Han

Alzheimer disease ； Futokadsura stem ； inflammation ； oxidative stress ； synaptophysin

The Chinese Journal of Physiology

58卷2期（2015 / 04 / 30）

104 - 113

英文

Futokadsura stem has been traditionally used to dispel wind-damp obstruction syndrome manifested as painful and stiff joints, tendon and muscle spasms, lower back pain, painful knees and pain from external injury. An aqueous extract of Futokadsura stem has previously been found to have neuro-protective effects in vitro. In this study, we aimed to investigate if the Futokadsura stem extract could protect the neuron in the brain of an Aβ-induced Alzheimer's Disease (AD)-like rat model by improving the learning and memory ability of the rats. Learning and memory ability of the rats were measured by the Morris water maze test. Neuronal morphology in the hippocampus was examined by HE staining. Expression levels of Aβ, TNF-α, IL-6 and synaptophysin (SYP) were measured by immunofluorescence. Nitric oxide (NO) and nitric oxide synthase (NOS) levels were measured by NO and NOS detecting kit. We found that aqueous extract of Futokadsura stem alleviated Aβ(25-35)-induced impairment of spatial learning and memory in the AD rats. Furthermore, the extract protected the neurons by decreasing the expression of Aβ, TNF-α and IL-6 and the content of NO and NOS in the brain, and increasing the expression of SYP in the hippocampus. Our data indicated that aqueous extract of Futokadsura stem improved the learning and memory ability of AD rats. The neuro-protective effect was accomplished probably by depressing inflammation and oxidative stress in the brain.

1. Qi, H.S.,Liu, P.,Gao, S.Q.,Diao, Z.Y.,Yang, L.L.,Xu, J.,Qu, X.,Han, E.J.(2009).Inhibitory effect of piperlonguminine/ dihydropiperlonguminine on the production of amyloid beta and APP in SKN-SH cells.Chinese J. Physiol.,52,160-168.
   連結：
2. Xia, W.,Zeng, J.P.,Chen, L.B.,Jiang, A.L.,Xiang, L.,Xu, J.,Cui, X.,Han, E.J.(2007).Inhibition of beta-amyloid precursor protein gene in SK-N-SH cells by piperlonguminine/dihydropiperlonguminine components separated from Chinese herbal medicine Futokadsura stem.Chinese J. Physiol.,50,157-163.
   連結：
3. Alkam, T.,Nitta, A.,Mizoguchi, H.,Saito, K.,Seshima, M.,Itoh, A.(2008).Restraining tumor necrosis factor-alpha by thalidomide prevents the Amyloid b-induced impairment of recognition memory in mice.Behav. Brain Res.,189,100-106.
4. Butterfield, D.A.,Perluigi, M.,Sultana, R.(2006).Oxidative stress in Alzheimer's disease brain: new insights from redox proteomics.Eur. J. Pharmacol.,545,39-50.
5. Castell, J.V.,Andus, T.,Kunz, D.,Heinrich, P.C.(1989).Interleukin-6: the major regulator of acute-phase protein synthesis in man and rat.Ann. N. Y. Acad. Sci.,557,87-99.
6. Choi, J.,Malakowsky, C.A.,Talent, J.M.,Conrad, C.C.,Carroll, C.A.,Weintraub, S.T.,Gracy, R.W.(2003).Anti-apoptotic proteins are oxidized by Abeta25-35 in Alzheimer's fibroblasts.Biochem. Biophys. Acta.,1637,135-141.
7. Fillit, H.,Ding, W.H.,Buee, L.,Kalman, J.,Altstiel, L.,Lawlor, B.,Wolf-Klein, G.(1991).Elevated circulating tumor necrosis factor levels in Alzheimer's disease.Neurosci. Lett.,129,318-320.
8. Glabe, C.G.(2006).Common mechanisms of amyloid oligomer pathogenesis in degenerative disease.Neurobiol. Aging,27,570-575.
9. Grace, E.A.,Busciglio, J.(2003).Aberrant activation of focal adhesion proteins mediates fibrillar amyloid β-induced neuronal dystrophy.J. Neurosci.,23,493-502.
10. Gruden, M.A.,Davudova, T.B.,Malisauskas, M.,Zamotin, V.V.,Sewell, R.D.,Voskresenskaya, N.I.,Kostanyan, I.A.,Sherstnev, V.V.,Morozova-Roche, L.A.(2004).Autoimmune responses to amyloid structures of Abeta(25-35) peptide and human lysozyme in the serum of patients with progressive Alzheimer's disease.Dement. Geriatr. Cogn. Disord.,18,165-171.
11. Han, E.J.,Hu, H.T.,He, X.Q.,Deng, X.M.,Lu, Y.,Zhou, H.T.(2004).Selective inhibition of haifengteng in gene expression of betaamyloid precursor protein.Chinese J. Clin. Rehabil.,8,2592-2593.
12. Han, E.J.,Joseph, R.(1998).Inhibition of β-amyloid precursor protein gene expression by haifengteng.J. Chinese Med.,23,691-693.
13. Hardy, J.(2003).The relationship between amyloid and tau.J. Mol. Neurosci.,20,203-206.
14. Hardy, J.A.,Higgins, G.A.(1992).Alzheimer's disease: the amyloid cascade hypothesis.Science,256,184-185.
15. Heyser, C.J.,Masliah, E.,Samimi, A.,Campbell, I.L.,Gold, L.H.(1997).Progressive decline in avoidance learning paralleled by inflammatory neurodegeneration in transgenic mice expressing interleukin 6 in the brain.Proc. Natl. Acad. Sci. USA,94,1500-1505.
16. Li, R.,Yang, L.,Lindholm, K.,Konishi, Y.,Yue, X.,Hampel, H.,Zhang, D.,Shen, Y.(2004).Tumor necrosis factor death receptor signaling cascade is required for amyloid-beta protein-induced neuron death.J. Neurosci.,24,1760-1771.
17. Maurice, T.,Lockhart, B.P.,Privat, A.(1996).Amnesia induced in mice by centrally administered b-amyloid peptides involves cholinergic dysfunction.Brain Res.,706,181-193.
18. Meunier, J.,Ieni, J.,Maurice, T.(2006).The anti-amnesic and neuro-protective effects of donepezil against amyloid beta 25-35 peptideinduced toxicity in mice involve an interaction with the sigma 1 receptor.Brit. J. Pharmacol.,149,998-1012.
19. Palmer, A.M.(2002).Pharmacotherapy for Alzheimer's disease: progress and prospects.Trends in Pharmacol. Sci.,23,426-433.
20. Pike, C.J.,Walencewicz-Wasserman, A.J.,Kosmoski, J.,Cribbs, D.H.,Glabe, C.G.,Cotman, C.W.(1995).Structure-activity analyses of β-amyloid peptides: contribution of the β25-35 region to aggregation and neurotoxicity.J. Neurochem.,64,253-265.
21. Selmaj, K.W.,Farooq, M.,Norton, W.T.,Raine, C.S.,Brosnan, C.F.(1990).Proliferation of astrocytes in vitro in response to cytokines. A primary role for tumor necrosis factor.J. Immunol.,144,129-135.
22. Seltzer, B.(2007).Donepezil: an update.Expert Opin. Pharmacother,8,1011-1023.
23. Shen, T.Y.,Hwang, S.B.,Chang, M.N.,Doebber, T.W.,Lam, M.T.,Wu, M.S.,Wang, X.,Han, G.Q.,Li, R.Z.(1985).Characterization of a platelet-activating factor receptor antagonist isolated from haifengteng (Piper futokadsura): Specific inhibition of in vitro and in vivo platelet-activating factor-induced effects.Proc. Natl. Acad. Sci. USA,82,672-676.
24. Tohda, C.,Matsumoto, N.,Zou, K.,Meselhy, M.R.,Komatsu, K.(2004).Aβ(25-35)-induced memory impairment, axonal atrophy, and synaptic loss are ameliorated by M1, A metabolite of protopanaxadiol-type saponins.Neuropsychopharmacology,29,860-868.
25. Tohda, C.,Tamura, T.,Komatsu, K.(2003).Repair of amyloid β(25-35)-induced memory impairment and synaptic loss by a Kampo formula, Zokumei-to.Brain Res.,990,141-147.
26. Tran, M.H.,Yamada, K.,Olariu, A.,Mizuno, M.,Ren, X.H.,Nabeshima, T.(2001).Amyloid beta-peptide induces nitric oxide production in rat hippocampus: association with cholinergic dysfunction and amelioration by inducible nitric oxide synthase inhibitors.FASEB J.,15,1407-1409.
27. Trubetskaya, V.V.,Stepanichev, M.Y.,Onufriev, M.V.,Lazareva, N.A.,Markevich, V.A.,Gulyaeva, N.V.(2003).Administration of aggregated beta-amyloid peptide25-35 induces changes in long-term potentiation in the hippocampus in vivo.Neurosci. Behav. Physiol.,33,95-98.
28. Tuppo, E.E.,Arias, H.R.(2005).The role of inflammation in Alzheimer's disease.Int. J. Biochem. Cell Biol.,37,289-305.
29. Walsh, D.M.,Klyubin, I.,Fadeeva, J.V.,Cullen, W.K.,Anwyl, R.,Wolfe, M.S.,Rowan, M.J.,Selkoe, D.J.(2002).Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo.Nature,416,535-539.
30. Yankner, B.A.,Duffy, L.K.,Kirschner, D.A.(1990).Neurotrophic and neurotoxic effects of amyloid β protein: reversal by tachykinin neuropeptides.Science,250,279-282.
31. Yao, J.Y.,Han, E.J.,Cui, X.,Yang, L.L.,Zeng, J.P.,Hao, J.R.,Fu, Z.T.(2007).Caulis Piperis Kadsura negatively regulates the expression of amyloid precursor protein in SK-N-SH cells.J. Beijing Univ. Tradit. Chinese Med.,30,314-316.