초록

본 연구과제를 통하여 여러 가지 퇴행성질환의 발병 및 진행에서 중요한 역학을 하는 뇌소교세포의 활성화를 isoflavones 및 그 대사체들이 효과적으로 억제함을 보였음. 특히 in vitro에서 항염증효과가 가장 뛰어난 irisolidone을 중심으로 구체적인 작용기전을 분석하였고 in vivo에서 뇌졸중 억제효과를 규명하였음. 또한 이소프라본의 structure-activity relationship을 규명하였음. 이러한 결과는 퇴행성 뇌질환 치료제 개발을 위한 이소프라본의 임상시험에 토대를 제공해 주는 것으로 사료됨.

Abstract ▼

I. Purpose of Project
The aim of this project is to investigate whether isoflavones and its metabolites suppress microglial activation, and then identify their detail molecular mechanisms. Based on in vitro data, the therapeutic effects on ischemic stroke will be examined by using in vivo animal

I. Purpose of Project
The aim of this project is to investigate whether isoflavones and its metabolites suppress microglial activation, and then identify their detail molecular mechanisms. Based on in vitro data, the therapeutic effects on ischemic stroke will be examined by using in vivo animal models. Ultimately, the results may be applied to clinical study for development of effective therapeutics for various neurodegenerative diseases.
II. Project Contents
${\blacktriangleright}$ Comparison and analysis of the effects of 6 kinds of isoflavones on the expression of pro-and anti-inflammatory cytokines, iNOS in activated microglia.
${\blacktriangleright}$ Examine the effects of isoflavones on inflammatory signaling molecules including NF-k8, AP1, CREB, MAP kinases, and JAK/STAT.
${\blacktriangleright}$ After selection of most effective anti-inflammatory isoflavone, test its effect on neuronal cell death caused by cerebral ischemia and on the number, migration of activated microglia.
${\blacktriangleright}$ Through this study, anti-inflammatory mechanisms of isoflavones will be identified. Furthermore, by analysis of structure-activity relationship, effective therapeutic structures for various neurodegenerative diseases will be elucidated.
III. Results
${\blacktriangleright}$ The effect of isoflavones and its metabolites on the production of TNF-${\alpha}$, IL-1${\beta}$, NO were examined and it was found that the anti-inflammatory effects of isoflavone metabolites are more prominent than the glycoside isoflavones.
${\blacktriangleright}$ Anti-inflammatory mechanisms of isoflavones metabolites were identified by molecular biology methods. In particular, it was found that irisolidone exerts anti-inflammatory effect through ERK, NF-k8 pathway. More detail signaling mechansims were analyzed.
${\blacktriangleright}$ Kakkalide siganificantly reduced the infact size in ischemic stroke animal models. Activation and migration of microglia were also suppressed by isoflavones.
${\blacktriangleright}$ Through this study, anti-inflammatory mechanisms of isoflavones was identified and the relationship between anti-inflammation and neuroprotection was elucidated. Furthermore, by analysis of structure-activity relationship, effective therapeutic structure for neurodegenerative diseases was elucidated.
IV. Application
${\blacktriangleright}$ Understanding the mechanisms underlying microglial activation and inactivation, which play an important role in neuronal cell death.
${\blacktriangleright}$ By elucidating structure-activity relationship, more effective therapeutic structure for neurodegenerative diseases will be identified.
${\blacktriangleright}$Provide the in vitro and in vivo data for developing isoflavones as therapeutic agents for various neurodegenerative diseases.

목차 Contents

• 표지...1
• I. 총괄현황...2
• II. 총괄연구과제 연구결과...28
• 1. 연구개발과제의 배경 및 필요성...29
• 2. 국내외 기술개발 현황...32
• 3. 연구개발과제의 추진체계...34
• 4. 연구개발수행 내용 및 결과...35
• 5. 목표달성도 및 관련분야 기여도...51
• 6. 향후 연구성과 추진계획...52
• 7. 연구개발결과의 파급효과...53
• 8. 연구개발결과의 활용계획...54
• 9. 연구개발과정에서 수집한 해외과학기술정보...54
• 10. 참고문헌...54
• IV. 첨부서류...56
• 1. 자체평가의견서...57
• 2. 연구성과 실적 증빙서류...62
• 3. 기타 요청서류...62
• [양식 2] 최종보고서 평가 면제요청서(중개연구 논문성과 달성)...63