Einzeltreffer — DigiBib

Effective therapeutic drugs for prevent or reverse the pathobiology of Alzheimer's disease (AD) have not been developed. Icariin (ICA), a prenylated flavonol glycoside derived from the traditional Chinese herb Epimedium sagittatum, exerts a variety of pharmacological activities and shows promise in the treatment and prevention of AD. This study investigated the neuroprotective effects of ICA in SAMP8 mice model of aspects of early AD and explored potential underlying mechanisms. Our results showed that intragastric administration of ICA could reverse the learning and memory impairment of SAMP8 mice in the Morris water maze. Western blot of hippocampal specimens revealed that ICA down-regulated the expression of BACE1 to reduce the expression of cytotoxic Aβ1-42. Furthermore, ICA siginificantly increase the Bcl-2/Bax ratio by increasing the expression of anti-apoptotic protein Bcl-2, and decreasing the expression of pro-apoptotic protein Bax, and thus inhibit neurons apoptosis. These findings indicate that ICA could improve cognitive deficits by reducing the deposition of β1-42 and inhibition of neurons apoptosis and provide further evidence for the clinical efficacy of ICA in the treatment of AD.

Titel:	Icariin improves cognitive deficits by reducing the deposition of β-amyloid peptide and inhibition of neurons apoptosis in SAMP8 mice.
Autor/in / Beteiligte Person:	Wu, J ; Qu, JQ ; Zhou, YJ ; Li, YY ; Huang, NQ ; Deng, CM ; Luo, Y
Link:	Zum Volltext
Zeitschrift:	Neuroreport, Jg. 31 (2020-06-07), Heft 9, S. 663-671
Veröffentlichung:	London, England : Lippincott Williams & Wilkins ; <i>Original Publication</i>: Oxford, UK : Rapid Communications of Oxford Ltd., [1990-, 2020
Medientyp:	academicJournal
ISSN:	1473-558X (electronic)
DOI:	10.1097/WNR.0000000000001466
Schlagwort:	Animals Cognitive Dysfunction prevention & control Disease Models, Animal Male Amyloid beta-Peptides metabolism Apoptosis drug effects Cognitive Dysfunction metabolism Flavonoids administration & dosage Neurons drug effects Neurons metabolism Neuroprotective Agents administration & dosage
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Neuroreport] 2020 Jun 07; Vol. 31 (9), pp. 663-671. MeSH Terms: Amyloid beta-Peptides / metabolism ; Apoptosis / drug effects ; Cognitive Dysfunction / metabolism ; Flavonoids / administration & dosage ; Neurons / drug effects ; Neurons / metabolism ; Neuroprotective Agents / *administration & dosage ; Animals ; Cognitive Dysfunction / prevention & control ; Disease Models, Animal ; Male References: Wortmann M. Dementia: a global health priority - highlights from an ADI and World Health Organization report. Alzheimers Res Ther. 2012; 4:40. ; Selkoe DJ. Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev. 2001; 81:741–766. ; Wood H. Alzheimer disease: localized proteomics distinguishes AD subtypes. Nat Rev Neurol. 2017; 13:260. ; Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E, et al. Alzheimer’s disease. Lancet (London, England). 2011; 377:1019–1031. ; Li F, Dong HX, Gong QH, Wu Q, Jin F, Shi JS. Icariin decreases both APP and Aβ levels and increases neurogenesis in the brain of Tg2576 mice. Neuroscience. 2015; 304:29–35. ; Bachurin SO, Bovina EV, Ustyugov AA. Drugs in clinical trials for Alzheimer’s disease: the major trends. Med Res Rev. 2017; 37:1186–1225. ; Karran E, Mercken M, De Strooper B. The amyloid cascade hypothesis for Alzheimer’s disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov. 2011; 10:698–712. ; Benilova I, Karran E, De Strooper B. The toxic Aβ oligomer and Alzheimer’s disease: an emperor in need of clothes. Nat Neurosci. 2012; 15:349–357. ; Haass C, Selkoe DJ. Cellular processing of beta-amyloid precursor protein and the genesis of amyloid beta-peptide. Cell. 1993; 75:1039–1042. ; Habib A, Sawmiller D, Tan J. Restoring soluble amyloid precursor protein α functions as a potential treatment for Alzheimer’s disease. J Neurosci Res. 2017; 95:973–991. ; Deng J, Habib A, Obregon DF, Barger SW, Giunta B, Wang YJ, et al. Soluble amyloid precursor protein alpha inhibits tau phosphorylation through modulation of GSK3beta signaling pathway. J Neurochem. 2015; 135:630–637. ; Sze SC, Tong Y, Ng TB, Cheng CL, Cheung HP. Herba Epimedii: anti-oxidative properties and its medical implications. Molecules. 2010; 15:7861–7870. ; Zhou J, Wu J, Chen X, Fortenbery N, Eksioglu E, Kodumudi KN, et al. Icariin and its derivative, ICT, exert anti-inflammatory, anti-tumor effects, and modulate myeloid derived suppressive cells (MDSCs) functions. Int Immunopharmacol. 2011; 11:890–898. ; Li S, Dong P, Wang J, Zhang J, Gu J, Wu X, et al. Icariin, a natural flavonol glycoside, induces apoptosis in human hepatoma SMMC-7721 cells via a ROS/JNK-dependent mitochondrial pathway. Cancer Lett. 2010; 298:222–230. ; Yang L, Lu D, Guo J, Meng X, Zhang G, Wang F, et al. Icariin from Epimedium brevicornum Maxim promotes the biosynthesis of estrogen by aromatase (CYP19). J Ethnopharmacol. 2013; 145:715–721. ; Ma H, He X, Yang Y, Li M, Hao D, Jia Z, et al. The genus Epimedium: an ethnopharmacological and phytochemical review. J Ethnopharmacol. 2011; 134:519–541. ; Liu B, Xu C, Wu X, Liu F, Du Y, Sun J, et al. Icariin exerts an antidepressant effect in an unpredictable chronic mild stress model of depression in rats and is associated with the regulation of hippocampal neuroinflammation. Neuroscience. 2015; 294:193–205. ; Nie J, Luo Y, Huang XN, Gong QH, Wu Q, Shi JS, et al. Icariin inhibits beta-amyloid peptide segment 25-35 induced expression of beta-secretase in rat hippocampus. Eur J Pharmacol. 2010; 626:213–218. ; Urano T, Tohda C. Icariin improves memory impairment in Alzheimer’s disease model mice (5xFAD) and attenuates amyloid beta-induced neurite atrophy. Phytother Res: PTR. 2010; 24:1658–1663. ; Jin F, Gong QH, Xu YS, Wang LN, Jin H, Li F, et al. Icariin, a phosphodiesterase-5 inhibitor, improves learning and memory in APP/PS1 transgenic mice by stimulation of NO/cGMP signalling. Int J Neuropsychopharmacol. 2014; 17:871–881. ; Zhang L, Shen C, Chu J, Zhang R, Li Y, Li L, et al. Icariin decreases the expression of APP and BACE-1 and reduces the beta-amyloid burden in an APP transgenic mouse model of Alzheimer’s disease. Int J Biol Sci. 2014; 10:181–191. ; Rhea EM, Banks WA. The SAMP8 mouse for investigating memory and the role of insulin in the brain. Exp Gerontol. 2017; 94:64–68. ; Morris R. Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods. 1984; 11:47–60. ; Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc. 2006; 1:848–858. ; Kitamura Y, Shimohama S, Kamoshima W, Ota T, Matsuoka Y, Nomura Y, et al. Alteration of proteins regulating apoptosis, Bcl-2, Bcl-x, Bax, Bak, Bad, ICH-1 and CPP32, in Alzheimer’s disease. Brain Res. 1998; 780:260–269. ; Czabotar PE, Lessene G, Strasser A, Adams JM. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol. 2014; 15:49–63. ; Zong N, Li F, Deng Y, Shi J, Jin F, Gong Q. Icariin, a major constituent from Epimedium brevicornum, attenuates ibotenic acid-induced excitotoxicity in rat hippocampus. Behav Brain Res. 2016; 313:111–119. ; Sheng C, Xu P, Zhou K, Deng D, Zhang C, Wang Z. Icariin attenuates synaptic and cognitive deficits in an Aβ1-42-induced rat model of Alzheimer’s disease. Biomed Res Int. 2017; 2017:7464872. ; Vattemi G, Nogalska A, King Engel W, D’Agostino C, Checler F, Askanas V. Amyloid-beta42 is preferentially accumulated in muscle fibers of patients with sporadic inclusion-body myositis. Acta Neuropathol. 2009; 117:569–574. ; Heneka MT, Sastre M, Dumitrescu-Ozimek L, Dewachter I, Walter J, Klockgether T, Van Leuven F. Focal glial activation coincides with increased BACE1 activation and precedes amyloid plaque deposition in APP[V717I] transgenic mice. J Neuroinflammation. 2005; 2:22. Substance Nomenclature: 0 (Amyloid beta-Peptides) ; 0 (Flavonoids) ; 0 (Neuroprotective Agents) ; VNM47R2QSQ (icariin) Entry Date(s): Date Created: 20200520 Date Completed: 20210818 Latest Revision: 20210818 Update Code: 20240513

Klicken Sie ein Format an und speichern Sie dann die Daten oder geben Sie eine Empfänger-Adresse ein und lassen Sie sich per Email zusenden.

BibTeX Citavi, JabRef, u.a.
(Literaturverwaltung)

PDF kein Volltext!
(Merkzettel, Notizen)

RIS Endnote, Citavi u.a.
(Literaturverwaltung)

MODS
(XML zur Weiterverarbeitung)

oder

Wählen Sie das für Sie passende Zitationsformat und kopieren Sie es dann in die Zwischenablage, lassen es sich per Mail zusenden oder speichern es als PDF-Datei.

Gewünschter Zitations-Stil:

oder

Bitte prüfen Sie, ob die Zitation formal korrekt ist, bevor Sie sie in einer Arbeit verwenden. Benutzen Sie gegebenenfalls den "Exportieren"-Dialog, wenn Sie ein Literaturverwaltungsprogramm verwenden und die Zitat-Angaben selbst formatieren wollen.

Icariin improves cognitive deficits by reducing the deposition of β-amyloid peptide and inhibition of neurons apoptosis in SAMP8 mice.