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Cerebrovascular smooth muscle cells (SMCs) hyperplasia is an important contributor to cerebrovascular remodeling during hypertension. The aim of present study was to investigate the effects of Icariin on cerebrovascular SMCs proliferation and remodeling and the underlying mechanisms. The results revealed that Icariin administration attenuated the enhanced basilar artery constriction in angiotensin II (AngII)-induced hypertension rat model, as well as the inhibition of basilar artery diameter reduction in response to AngII and phenylephrine. In addition, histological analyses showed that Icariin also significantly ameliorated basilar artery remodeling in AngII hypertensive rats. In human brain vascular SMCs (HBVSMCs), AngII-induced cell proliferation, migration and invasion were markedly inhibited by Icariin treatment. Moreover, Icariin treatment largely limited AngII-induced the increase of reactive oxygen species (ROS) production in HBVSMCs, which was closely associated with cell proliferation. Analysis of the mechanisms showed that Icariin decreased ROS production via inhibiting NADPH oxidase activity but not mitochondria-derived ROS production. Further, Icariin promoted Nox2 degradation and consequently reduced its protein expression. In conclusion, these findings demonstrate that Icariin attenuates cerebrovascular SMCs hyperplasia and subsequent remodeling through inhibiting Nox2-containing NADPH oxidase activation, suggesting Icariin may be a potential therapeutic agent to prevent the onset and progression of stroke.

Titel:	Icariin ameliorates angiotensin II-induced cerebrovascular remodeling by inhibiting Nox2-containing NADPH oxidase activation.
Autor/in / Beteiligte Person:	Dong, H ; Ming, S ; Fang, J ; Li, Y ; Liu, L
Link:	Zum Volltext
Zeitschrift:	Human cell, Jg. 32 (2019), Heft 1, S. 22-30
Veröffentlichung:	2011- : Tokyo : Springer ; <i>Original Publication</i>: Tōkyō-to : Hito Saibō Kenkyūkai : Kanishobo, Shōwa 63-nen [1988]-, 2019
Medientyp:	academicJournal
ISSN:	1749-0774 (electronic)
DOI:	10.1007/s13577-018-0220-3
Schlagwort:	Animals Basilar Artery pathology Cell Movement drug effects Cell Proliferation drug effects Cells, Cultured Disease Models, Animal Flavonoids therapeutic use Humans Hyperplasia Hypertension chemically induced Muscle, Smooth, Vascular metabolism Rats, Sprague-Dawley Reactive Oxygen Species metabolism Stroke etiology Stroke prevention & control Angiotensin II adverse effects Brain blood supply Drugs, Chinese Herbal Flavonoids pharmacology Hypertension pathology Hypertension physiopathology Muscle, Smooth, Vascular cytology Muscle, Smooth, Vascular pathology NADPH Oxidase 2 antagonists & inhibitors NADPH Oxidase 2 metabolism NADPH Oxidases antagonists & inhibitors NADPH Oxidases metabolism Phytotherapy Vascular Remodeling drug effects
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Hum Cell] 2019 Jan; Vol. 32 (1), pp. 22-30. <i>Date of Electronic Publication: </i>2018 Nov 01. MeSH Terms: Drugs, Chinese Herbal* ; Phytotherapy* ; Angiotensin II / adverse effects ; Brain / blood supply ; Flavonoids / pharmacology ; Hypertension / pathology ; Hypertension / physiopathology ; Muscle, Smooth, Vascular / cytology ; Muscle, Smooth, Vascular / pathology ; NADPH Oxidase 2 / antagonists & inhibitors ; NADPH Oxidase 2 / metabolism ; NADPH Oxidases / antagonists & inhibitors ; NADPH Oxidases / metabolism ; Vascular Remodeling / drug effects ; Animals ; Basilar Artery / pathology ; Cell Movement / drug effects ; Cell Proliferation / drug effects ; Cells, Cultured ; Disease Models, Animal ; Flavonoids / therapeutic use ; Humans ; Hyperplasia ; Hypertension / chemically induced ; Muscle, Smooth, Vascular / metabolism ; Rats, Sprague-Dawley ; Reactive Oxygen Species / metabolism ; Stroke / etiology ; Stroke / prevention & control References: Hypertension. 2006 Oct;48(4):534-40. (PMID: 16923993) ; Hypertension. 2006 Dec;48(6):1012-7. (PMID: 17060505) ; Biochimie. 2007 Sep;89(9):1107-12. (PMID: 17400358) ; Nat Clin Pract Cardiovasc Med. 2008 Jun;5(6):338-49. (PMID: 18461048) ; Curr Hypertens Rep. 2009 Jun;11(3):182-9. (PMID: 19442327) ; Hypertension. 2010 Jun;55(6):1461-7. (PMID: 20439821) ; Microvasc Res. 2010 Dec;80(3):445-52. (PMID: 20600163) ; Circulation. 2011 Feb 1;123(4):e18-e209. (PMID: 21160056) ; J Pharm Pharmacol. 2011 Apr;63(4):541-9. (PMID: 21401606) ; J Mol Cell Cardiol. 2012 Feb;52(2):454-63. (PMID: 21978629) ; Circulation. 2012 Feb 7;125(5):697-707. (PMID: 22215857) ; Antioxid Redox Signal. 2013 Oct 1;19(10):1074-84. (PMID: 22429119) ; Clin Sci (Lond). 2013 May;124(10):597-615. (PMID: 23379642) ; Nature. 2014 May 8;509(7499):235-9. (PMID: 24739962) ; Cell Death Dis. 2014 Aug 14;5:e1370. (PMID: 25118930) ; Life Sci. 2015 Apr 1;126:57-68. (PMID: 25634110) ; Biosci Rep. 2015 Aug 26;35(5):null. (PMID: 26310573) ; Biomed Res Int. 2015;2015:926567. (PMID: 26636103) ; Zhonghua Yi Xue Za Zhi. 2015 Dec 1;95(45):3701-4. (PMID: 26849936) ; Zhongguo Zhong Yao Za Zhi. 2015 Nov;40(21):4234-9. (PMID: 27071263) ; Exp Cell Res. 2016 Aug 15;346(2):147-56. (PMID: 27364911) ; Free Radic Biol Med. 2016 Dec;101:163-175. (PMID: 27746262) ; Biomed Pharmacother. 2017 Apr;88:823-831. (PMID: 28171848) ; Zhongguo Zhong Yao Za Zhi. 2016 Oct;41(19):3655-3660. (PMID: 28925164) ; Adv Exp Med Biol. 2017;967:1-11. (PMID: 29047077) ; Redox Biol. 2018 Apr;14:656-668. (PMID: 29175753) ; Exp Ther Med. 2017 Dec;14(6):6105-6112. (PMID: 29285165) ; Eur J Pharmacol. 2018 Jun 15;829:102-111. (PMID: 29665366) ; J Int Med Res. 2018 Jun;46(6):2371-2385. (PMID: 29734850) Contributed Indexing: Keywords: Cerebrovascular remodeling; Icariin; NADPH; Nox2; Proliferation; Reactive oxygen specie Substance Nomenclature: 0 (Drugs, Chinese Herbal) ; 0 (Flavonoids) ; 0 (Reactive Oxygen Species) ; 11128-99-7 (Angiotensin II) ; EC 1.6.3.- (Cybb protein, rat) ; EC 1.6.3.- (NADPH Oxidase 2) ; EC 1.6.3.- (NADPH Oxidases) ; VNM47R2QSQ (icariin) Entry Date(s): Date Created: 20181103 Date Completed: 20190308 Latest Revision: 20200225 Update Code: 20240513

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Icariin ameliorates angiotensin II-induced cerebrovascular remodeling by inhibiting Nox2-containing NADPH oxidase activation.