Lee, Kyung-Mi Park, Taejin Kim, Min-Seon Park, Jin-Soo Chi, Won-Jae Kim, Seung-Young 2024-01-19T12:02:29Z 2024-01-19T12:02:29Z 2022-06-02 2022-05 1934-578X https://pubs.kist.re.kr/handle/201004/115207 Coumarins are phenolic compounds that are characterized by fused benzene and alpha-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 (PGE(2)), 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-kappa B) 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. English Natural Product Communications Anti-inflammatory Activities of 7,8-Dihydroxy-4-Methylcoumarin Acetylation Products via NF-kappa B and MAPK Pathways in LPS-Stimulated RAW 264.7 Cells Article 10.1177/1934578X221086893 1 Natural product communications, v.17, no.5 Natural product communications 17 5 Y scie scopus 000799071900001 Chemistry, Medicinal Food Science & Technology Pharmacology & Pharmacy Food Science & Technology Article NITRIC-OXIDE PRODUCTION DOWN-REGULATION RAW264.7 CELLS LIPOPOLYSACCHARIDE INHIBITION ACTIVATION SUPPRESSION FLAVONOIDS INFLAMMATION MEDIATORS kinase pathways anti-inflammation coumarin monoacetylation bioactivity nitric oxide