城西大学機関リポジトリJURAInvolvement of restoration of cerebral blood flow and maintenance of eNOS expression in the prophylactic protective effect of a novel ferulic acid derivative FAD012 against ischemia/reperfusion injury in rats

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Involvement of restoration of cerebral blood flow and maintenance of eNOS expression in the prophylactic protective effect of a novel ferulic acid derivative FAD012 against ischemia/reperfusion injury in rats

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ID	JOS-ijms24119663
著者：名前	浅野, 昂志/玄, 美燕/岩田, 直洋/高山, 淳/林, 浩輔/加藤, 洋介/青山, 隼也/周郷, 広史/松崎, 広和/袁, 博/神内, 伸也/日比野, 康英/坂本, 武史/岡崎, 真理
著者：別形式	Asano, Takashi / Xuan, Meiyan / Iwata, Naohiro / Takayama, Jun / Hayashi, Kousuke / Kato, Yosuke / Aoyama, Toshiya / Sugo, Hiroshi / Matsuzaki, Hirokazu / Yuan, Bo / Kamiuchi, Shinya / Hibino, Yasuhide / Sakamoto, Takeshi / Okazaki, Mari
著者：カナ	アサノ, タカシ/ゲン, ビエン/イワタ, ナオヒロ/タカヤマ, ジュン/ハヤシ, コウスケ/カトウ, ヨウスケ/アオヤマ, トシヤ/スゴウ, ヒロシ/マツザキ, ヒロカズ/エン, パク/カミウチ, シンヤ/ヒビノ, ヤスヒデ/サカモト, タケシ/オカザキ, マリ
著者：所属	城西大学大学院薬学研究科薬品作用学研究室 / 城西大学大学院薬学研究科医薬品化学研究室 / 城西大学薬学部生体防御学研究室 / 城西大学大学院薬学研究科医薬品化学研究室 / 城西大学大学院薬学研究科医薬品化学研究室 / 城西大学大学院薬学研究科医薬品化学研究室 / 城西大学大学院薬学研究科薬品作用学研究室 / 城西大学大学院薬学研究科薬品作用学研究室 / 城西大学大学院薬学研究科薬品作用学研究室 / 城西大学大学院薬学研究科薬品作用学研究室 / 城西大学薬学部生体防御学研究室 / 城西大学薬学部生体防御学研究室 / 城西大学大学院薬学研究科医薬品化学研究室 / 城西大学大学院薬学研究科薬品作用学研究室
著者：所属(別形式）	Josai University, Faculty of Pharmaceutical Sciences, Laboratory of Pharmacology / Josai University, Faculty of Pharmaceutical Sciences, Laboratory of Organic and Medicinal Chemistry / Josai University, Faculty of Pharmaceutical Sciences, Laboratory of Immunobiochemistry / Josai University, Faculty of Pharmaceutical Sciences, Laboratory of Organic and Medicinal Chemistry / Josai University, Faculty of Pharmaceutical Sciences, Laboratory of Organic and Medicinal Chemistry / Josai University, Faculty of Pharmaceutical Sciences, Laboratory of Organic and Medicinal Chemistry / Josai University, Faculty of Pharmaceutical Sciences, Laboratory of Pharmacology / Josai University, Faculty of Pharmaceutical Sciences, Laboratory of Pharmacology / Josai University, Faculty of Pharmaceutical Sciences, Laboratory of Pharmacology / Josai University, Faculty of Pharmaceutical Sciences, Laboratory of Pharmacology / Josai University, Faculty of Pharmaceutical Sciences, Laboratory of Immunobiochemistry / Josai University, Faculty of Pharmaceutical Sciences, Laboratory of Immunobiochemistry / Josai University, Faculty of Pharmaceutical Sciences, Laboratory of Organic and Medicinal Chemistry / Josai University, Faculty of Pharmaceutical Sciences, Laboratory of Pharmacology
著者版フラグ	publisher
出版地	Basel
出版者	MDPI
冊子ISSN	16616596
電子ISSN	14220067
掲載誌名	International Journal of Molecular Sciences
巻	24
号	11
刊行年月	2023-06
開始ページ	1
終了ページ	18
コンテンツ作成日	2023-04-13
コンテンツ修正日	2023-05-30
コンテンツ登録日	2023-07-19
識別番号：DOI	info:doi/10.3390/ijms24119663
識別番号：DOI（リンク）	https://doi.org/10.3390/ijms24119663
PubMed番号	37298615
抄録	Tissue plasminogen activator, aiming to restore cerebral blood flow (CBF), has been used for acute ischemic strokes in clinics; however, its narrow therapeutic time window remains a serious concern. To develop novel prophylactic drugs to alleviate cerebral ischemia/reperfusion injuries, ferulic acid derivative 012 (FAD012) was synthesized and showed comparable antioxidant properties to ferulic acid (FA) and probably possesses the potent ability to cross the blood–brain barrier. A more potent cytoprotective effect of FAD012 against H2O2-induced cytotoxicity in PC12 cells was also observed. In vivo toxicity was not observed in rats given a long-term oral administration of FAD012, indicating its good tolerability. A one-week-course oral administration of FAD012 significantly alleviated middle cerebral artery occlusion (MCAO)-induced cerebral ischemia/reperfusion injuries in rats, accompanied by the restoration of CBF and endothelial nitrogen oxide synthetase (eNOS) expression. Treatment with FAD012 significantly restored the cell viability and eNOS expression damaged by H2O2, used to mimic MCAO-triggered oxidative stress, in rat brain microvascular endothelial cells. Our findings suggested that FAD012 protected the viability of vascular endothelium and maintained eNOS expression, ultimately contributing to the restoration of CBF, and may provide a rationale for the development of FAD012 into an effective prophylactic drug for patients at high risk of stroke.
キーワード	ferulic acid derivative/middle cerebral artery occlusion/ischemia/reperfusion injury/cerebral blood flow/oxidative stress/endothelial nitrogen oxide synthetase
注記	p.18 Article number: 9663 Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
言語	eng
資源タイプ	text
ジャンル	01学術雑誌論文 / Journal Article
フォーマット	application/pdf
権利	Copyright © 2023 by the authors.
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