P-20 オニヒトデ由来の新規ステロイド配糖体の構造、活性および作用機構(ポスター発表の部)

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Exogenous low-molecular-weight compounds that mimic and/or enhance the neuritogenic activity of nerve growth factor (NGF) might be developed as promising therapeutic drugs to treat neurodegenerative diseases such as Alzheimer's disease. We have searched for such substances from marine sources, and found 23 steroid glycosides including 15 novel ones named "acanthasterosides" from the Okinawan crown-of-thorn starfish Acanthaster planci ('Onihitode' in Japanese). The efforts have been made to obtain the basis for developing leads for therapeutic agents. The structures were determined by spectroscopic and chemical methods. These steroid glycosides consist of a highly oxidized steroid core and one or two sugars (usually pentoses) at C-3 and/or side chain. These can be structurally classified into 4 types, and six acanthasterosides (type B) possessing one pentose at C-3 and another sugar at the side chain branch (C-28) showed significant NGF-like neuritogenic activity. NGF binds to TrkA to promote its phosphorylation, but acanthasteroside B3 did not. On the other hand, acanthasteroside B3 promoted phosphorylation of MAP kinase (ERK1/2, p38) and Akt. Upstream pathways are still unclear. To evaluate an effect of acanthasterosides for memory or learning, a mixture of steroid glycoside containing acanthasteroside B1 was subcutaneously administered to middle aged mice (32-40 weeks). Y-maze tests showed that the short-term memory of the aged mice was improved to a level of young mice.
天然有機化合物討論会の論文
2006-09-15

P-20 オニヒトデ由来の新規ステロイド配糖体の構造、活性および作用機構(ポスター発表の部)

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