| Project/Area Number |
16590080
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
MIURA Toshiaki Hokkaido Univ., Grad.School of Pharm., Prof., 大学院・薬学研究科, 教授 (10091505)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUDA Tadashi Hokkaido Univ., Grad.School of Pharm., Prof., 大学院・薬学研究科, 教授 (20212219)
TAMOTO Kouichi Hokkaido Iryou Univ., Fac.of Pharm., Asso.Prof., 薬学部, 助教授 (50088861)
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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 |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Ozonide / Cyclooxygenase-2 / anti-inflammatory action / Signaling pathway / NFкB / MAP kinase / TNF-α / IкBα / 抗炎症薬 |
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| Research Abstract |
Ozonized olive oil has been reported to exert anti-inflammatory effect. However, the details of chemical structure of ozonized olive oil and its action mechanism have long been unclear. We have recently demonstrated that the major component of the ozonized olive oil is triozonide of triolein. In this study, we identified several minor components of ozonized olive oil, including "cross ozonides" of low and high molecular weight. In addition, to elucidate the anti-inflammatory action mechanism of ozonized olive oil, we investigated the effects of ozonized olive oil and methyl oleate ozonides on the generation of PGE_2 and the expression of Cyclooxygenase-2 (COX-2) in Lipopolysaccharide (LPS)-stimulated macrophage-like THP-1 cells. Olive oil, methyl oleate and their ozonides did not affect cell viability and morphology within a concentration used. LPS-induced COX-2 expression and PGE_2 generation in macrophage-like THP-1 cells were not affected by olive oil itself. However, ozonized olive oil inhibited both reactions in a concentration-dependent manner. Methyl oleate ozonides also inhibited COX-2 expression and PGE_2 generation whereas oleic acid and methyl oleate did not show such inhibitory effects. Such actions of ozonized olive oil and methyl oleate ozonide were shown to be due to their inhibitory effect on lкB phosphorylation which is required for Nuclear factor-kappa B (NFкB) activation and subsequent COX-2 gene transcription in LPS-stimulated macrophages. The inhibitory effect was also observed with ozonide having no functional group except for ozonide ring. In addition, ozonized olive oil and methyl oleate ozonide showed no effect on the phosphorylations of p38 and JNK, which are involved in the activation of AP-1. These results demonstrate that ozonized olive oil and methyl oleate ozonides suppress LPS-induced PGE_2 generation in macrophage-like THP-1 cells through inhibition of COX-2 gene transcription by suppressing the lкBαNFкB pathway.
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