Affiliation:
1. Sunmoon University, Chungnam, Korea
2. Natural Product Informatics Research Center, KIST Gangneung Institute of Natural Products, Korea Institute of Science and Technology (KIST), Gangwon-do, Korea
3. Microorganism Resources Division Biological Resources Research Department, National Institute of Biological Resource, Incheon, South Korea
Abstract
Coumarins are phenolic compounds that are characterized by fused benzene and α-pyrone rings. Among coumarin-based compounds, 7,8-dihydroxy-4-methylcoumarin (DHMC) has anti-inflammatory activities, but whether the level of this activity varies according to the degree of acetylation remains unknown. Therefore, we acetylated DHMC to yield monoacetylated 8-acetoxy-4-methylcoumarin (8AMC) and 7,8-diacetoxy-4-methylcoumarin (DAMC). We then compared the anti-inflammatory activities of DHMC with its acetylated derivatives and discovered a novel anti-inflammatory agent. We evaluated whether DHMC, 8AMC, and DAMC could inhibit lipopolysaccharide (LPS)-induced stimulation in RAW 264.7 cells. We found that DHMC, 8AMC, and DAMC induced a dose-dependent downregulation of nitric oxide (NO), prostaglandin E2 (PGE2), pro-inflammatory cytokine, inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2) expression at the mRNA and protein levels. Western blotting showed that DHMC, 8AMC, and DAMC inhibited phosphorylated mitogen-activated protein kinase (MAK), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38, and nuclear factor-kappa B (NF-κB) expression in a concentration-dependent manner. Furthermore, 8AMC was the most effective inhibitor with powerful anti-inflammatory activity. These results indicate that acetylation can improve the anti-inflammatory activity of natural precursors. We also discovered the new anti-inflammatory compounds 8AMC and DAMC.
Subject
Complementary and alternative medicine,Plant Science,Drug Discovery,Pharmacology,General Medicine
Cited by
2 articles.
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