Construction of an Aohitode saponin library and basic research for development of nervous disease therapy
| Project/Area Number |
16310151
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Living organism molecular science
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| Research Institution | Nagoya University |
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Principal Investigator |
OJIKA Makoto Nagoya University, Graduate School of Bioagricultural Sciences, Professor, 大学院・生命農学研究科, 教授 (50152492)
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| Co-Investigator(Kenkyū-buntansha) |
UCHIDA Koji Nagoya University, Graduate School of Bioagricultural Sciences, Associate Professor, 大学院・生命農学研究科, 助教授 (40203533)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2005: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2004: ¥7,300,000 (Direct Cost: ¥7,300,000)
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| Keywords | Blue starfish / Linckia laevigata / neurite outgrowth / nerve growth factor / PC12 cells / marine organisms / steroid glycoside / ERK / Linckia leavigata |
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| Research Abstract |
Structurally diverse novel saponins were found from the Okinawan blue starfish Linckia laevigata, and their NGF-like neuritogenic activity was demonstrated. The findings would provide important information for developing drug candidates for nervous diseases, such as Alzheimer's desease.
1. Isolation
The blue starfish was collected in Okinawa and extracted with MeOH. The extract was chromatographed on ODS followed by silica gel. Saponin fractions were further purified by HPLC to afford 21 saponin containing 17 novel metaboliytes.
2. Structural elucidation
On the basis of spectroscopic analysis as well as chemical derivatization, their structures were determined. The novel compounds were named linckosides. The common structure is steroidal core modified by one or two pentoses (xylose or arabinose) at C-3 and the side chain. The structural diversity was due to the number and nature of the pentoses, oxidation degree of the steroid core, carbon branching mode of the side chain, and O-methylation of sugars.
3. Biological activity
Nerve hrowth facter (NGF)-like neuritogenic activity was evaluated by using rat PC12 cells. The disaccharides that possess two pentoses at C-3 and the side chain were much more active than the monosaccharides that possess a xylose at C-3. The 2'-O-methylation of the xylose at C-3 increased twice the activity. The compounds possessing a xylose at the side chain were more active than those possessing an arabinose. The carbon branching at the side chain increased the activity. The NGF-enhancing activity was also evaluated in the presence of a low concentration of NF. All saponins showed significant NGF-enhancing activity.
4. Mode of action
The neuritogenic saponins were demonstrated to activate ERK by inducing its phosphorylation like NGF. However, they did not activate the NGF receptor TrkA The NGF-enhancing activity might be due to sustaining the phosphorylation of ERK by NGF at a low concentration.
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Report
(3 results)
Research Products
(9 results)
