| Project/Area Number |
26860072
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Natural medicines
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| Research Institution | Osaka University of Pharmaceutical Sciences |
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Principal Investigator |
Koike Atsushi 大阪薬科大学, 薬学部, 助手 (00625725)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | マクロファージ / 抗炎症 / 天然物 / アポトーシス / シコニン / 天然化合物 / LPS |
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| Outline of Final Research Achievements |
Macrophages play pivotal roles in inflammatory responses. Shikonin (SHK) and its derivatives (β-hydroxyisovalerylshikonin, acetylshikonin, and isobutylshikonin) are 1,4-naphthoquinone pigments extracted from the roots of Lithospermum erythrochizon. We investigated the effects of SHK derivatives on lipopolysaccharide (LPS)-treated macrophages. Low doses of SHK derivatives significantly induced macrophage cytotoxicity (mouse macrophage-like J774.1/JA-4 cells and mouse peritoneal macrophages) in the presence of LPS. SHK activated caspases-3 and -7, which led to DNA fragmentation, but this cytotoxicity was prevented through a pan-caspase inhibitor in LPS-treated JA-4 cells. Maximal cytotoxic effects were achieved when SHK was added immediately before LPS addition. These results indicate that SHK derivatives induced caspase-dependent apoptotic cell death of the LPS-treated macrophages and suggest that SHK acts during an early stage of LPS signaling.
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