Protective mechanism of FAD012, a ferulic acid derivative, against ischemic brain injury.
| Project/Area Number |
16K09255
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General internal medicine(including psychosomatic medicine)
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| Research Institution | Josai University |
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Principal Investigator |
OKAZAKI MARI 城西大学, 薬学部, 教授 (50272901)
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| Co-Investigator(Kenkyū-buntansha) |
松崎 広和 城西大学, 薬学部, 助教 (80582238)
坂本 武史 城西大学, 薬学部, 教授 (20187040)
玄 美燕 城西大学, 薬学部, 助手 (50711751)
日比野 康英 城西大学, 薬学部, 教授 (10189805)
岩田 直洋 城西大学, 薬学部, 助教 (50552759)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | フェルラ酸誘導体FAD012 / 虚血性脳血管障害 / 両側総頚動脈永久結紮（2VO） / 中大脳動脈閉塞・再灌流（MCAO/Re） / 脳血流維持作用 / 内皮型NO合成酵素（eNOS） / 脳保護薬 / 予防的治療薬 / フェルラ酸誘導体 / 両側総頚動脈結紮（2VO） / 内皮型一酸化窒素合成酵素（eNOS） / アポトーシス抑制 / 一酸化窒素（NO） / ラット脳虚血モデル / 硫化水素（H2S) / 脳保護作用 |
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| Outline of Final Research Achievements |
Stroke occurs suddenly, which leads to a poor prognosis. To discover a new preventive therapeutic agent that can protect brain against ischemic injury, we have designed and synthesized dozens of derivatives of ferulic acid (FA) and screened them in vitro. Chronic preventive administration of FAD012, one of the derivatives preserved cerebral blood flow (CBF) and markedly suppressed brain damage in rats treated with bilateral permanent carotid artery permanent occlusion (2VO) or middle cerebral artery occlusion/reperfusion (MCAO / Re). We showed that these effects involve the activation of nitric oxide endothelial synthase (eNOS) in cerebral blood vessels. Our study demonstrated that FAD012, designed from FA, had low toxicity, could be used as a long-term prophylactic agent, and reduced the brain damage after the sudden onset of acute-phase cerebral infarction through the maintenance of CBF during ischemia.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の学術的特色は、虚血性脳障害の予防・軽減を目的とし、フェルラ酸をシードとして創出した新規化合物の有効性を多岐にわたる研究分野を連結して検証し、安全性の高い脳保護薬の開発を目指すところにある。現在、脳梗塞に対する治療は、発症後の薬物療法が中心であり、治療の遅れによる重篤化が医療・介護の負担を増大させている。我々の研究成果により、FAD012は既存薬とは異なるメカニズムを有する安全な脳保護薬として、ハイリスク患者や既往歴のある患者の発症・再発予防および障害の軽減に貢献できる可能性が示された。
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Report
(4 results)
Research Products
(19 results)
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[Presentation] FAD012, a ferulic acid derivative, protects against middle cerebral artery occlusion (MCAO)-induced ischemic stroke by preserving cerebral blood flow in rats2018
Author(s)
Takashi Asano, Ryo Endo, Kosuke Hayashi, Yosuke Kato, Naohiro Iwata, Hirokazu Matsuzaki, Takeshi Sakamoto, Yasuhide Hibino, Mari Okazaki
Organizer
18th WORLD CONGRES OF BASIC AND CLINICAL PHARMACOLOGY
Related Report
Int'l Joint Research
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[Presentation] FAD012, a ferulic acid derivative, improves cerebral blood flow and enhances swallowing reflux in a rat chronic cerebral hypoperfusion model2018
Author(s)
Takashi Asano, Hirokazu Matsuzaki, Yosuke Kato, Kosuke Hayashi, Meiyan Xuan, Naohiro Iwata, Jun Takayama, Takeshi Sakamoto, Yasuhide Hibino, Mari Okazaki
Organizer
18th WORLD CONGRES OF BASIC AND CLINICAL PHARMACOLOGY
Related Report
Int'l Joint Research
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