A search of compounds with regulating activated macrophages

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860072
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Natural medicines
• Research Institution: Osaka University of Pharmaceutical Sciences
• Principal Investigator: Koike Atsushi 大阪薬科大学, 薬学部, 助手 (00625725)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: マクロファージ / 抗炎症 / 天然物 / アポトーシス

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.

Free Research Field

環境・衛生系薬学