Synthetic study on polymethoxyflavones: separation and enhancing of their biological activities
| Project/Area Number |
15K08032
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Drug development chemistry
|
|---|
| Research Institution | Teikyo University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
小佐野 博史 帝京大学, 薬学部, 教授 (40246020)
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
Miyata Yoshiki 帝京大学, 薬学部, 准教授 (20433881)
Tabata Hidetsugu 帝京大学, 薬学部, 講師 (80445634)
|
|---|
| Project Period (FY) |
2015-04-01 – 2018-03-31
|
| Project Status |
Completed (Fiscal Year 2017)
|
| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
|
|---|
| Keywords | ポリメトキシフラボン / 後発白内障 / 糖尿病網膜症 / 構造活性相関 / MMP-9 / ノビレチン / 白内障 / リン酸化 |
|---|
| Outline of Final Research Achievements |
Over the past two decades, increasing attention has been given to polymethoxyflavones (PMFs) because of their diverse bioactivities such as anticancer, antiinflammatory, antidiabetic, and neurotrophic activities. We demonstrated that nobiletin isolated from citrus plants attenuated MMP-9 enzymatic activity through the suppression of transcription for MMP-9 gene and augmentation of TIMP-1 production in retinal Mueller cells. Nobiletin regulated MMP-9 gene expression and TIMP-1 by inhibiting the PI3 K/Akt signaling pathway. We also observed the augmentation of inhibitory action against MMP-9 activity by 4'-demethylnobiletin. We believe that the enhancement of inhibitory action against MMP-9 activity by 4'-demethylnobiletin is through the dual inhibition on Erk1/2 and Akt phosphorylation. The SAR studies revealed that, for the enhancement of inhibitory action against MMP-9 enzymatic activity, demethylation at position 4' in B-ring was a key structural modification in Mueller cells.
|
Report
(4 results)
Research Products
(10 results)
