| Project/Area Number |
11470485
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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 |
Biological pharmacy
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
YAMAMOTO Itaru Okayama University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (20028848)
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| Co-Investigator(Kenkyū-buntansha) |
TAI Akihiro Okayama University, Faculty of Pharmaceutical Sciences, Research Assistant, 薬学部, 助手 (70284081)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥10,600,000 (Direct Cost: ¥10,600,000)
Fiscal Year 2000: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥7,600,000 (Direct Cost: ¥7,600,000)
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| Keywords | neuro-immune cross-talks / ascorbic acid / stable ascorbate derivatives / AA-2G / lipophilic ascorbate derivatives / 6-Acyl-AA-2G |
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| Research Abstract |
By use of a stable ascorbate, ascorbic acid 2-glucoside (AA-2G), as an ascorbate source, we have shown that ascorbic acid exhibits synergistic enhancing effects on antigen specific antibody productions and neurite outgrowth elicited by cytokines or chemical transmitters, although ascorbic acid alone was without effect or less effective. These findings suggest that ascorbic acid might have function in amplifying cytokine-dependent actions in neuro-immune cross-talks. In order to investigate and document this issue, here we attempted to prepare stable lipophilic ascorbate derivatives. We have chemically synthesized a series of stable and lipophilic ascorbate derivatives, 6-Acyl-AA-2G from AA-2G, with regiospecific acylation technique which we have developed, and shown that these acylated ascorbates led to marked increase in skin penetration and absorbance from intestinal tracts, compared with water soluble ascorbate and AA-2G. It was also demonstrated that these derivatives were enzymatically metabolized by a-glucosidase or esterase in tissues and cells to release ascorbic acid which express its physiological activities such as antiscorbutic activity and stimulation of collagen synthesis in vivo and in vitro. We have found that these acylated ascorbates are superior to ascorbate or AA-2G in the enhancing response of cyclic AMP-induced neurite outgrowth in PC12 cells and in the enhancement of IL-2-dependent antibody response in murine splenic B cells. These ascorbate derivatives will represent a useful tool to study a role of ascorbate in neuro-immune cross-talks functioned by cytokines and chemical transmitters.
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