Inhibitory effects of phloroglucinol derivatives from Mallotus japonicus on nitric oxide production by a murine macrophage-like cell line, RAW 264.7, activated by lipopolysaccharide and interferon-gamma.
An aqueous acetone extract of the pericarps of Mallotus japonicus (MJE) inhibited nitric oxide (NO) production by a murine macrophage-like cell line, RAW 264.7, which was activated by lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Seven phloroglucinol derivatives isolated from MJE exhibited inhibitory activity against NO production. Among these phloroglucinol derivatives, isomallotochromanol exhibited strong inhibitory activity toward NO production, exhibiting an IC(50) of 10.7 microM. MJE and the phloroglucinol derivatives significantly reduced both the induction of inducible nitric oxide synthase (iNOS) protein and iNOS mRNA expression. NO production by macrophages preactivated with LPS and IFN-gamma for 16 h was also inhibited by MJE and the phloroglucinol derivatives. Furthermore, MJE and the derivatives directly affected the conversion of L-[(14)C]arginine to L-[(14)C]citrulline by the cell extract. These results suggest that MJE and the phloroglucinol derivatives have the pharmacological ability to suppress NO production by activated macrophages. They inhibited NO production by two mechanisms: reduction of iNOS protein induction and inhibition of enzyme activity.
Ishii
R
R
Saitama Instiute of Public Health, Japan.
Horie
M
M
Saito
K
K
Arisawa
M
M
Kitanaka
S
S
D000818:Animals; D002460:Cell Line; D019665:Euphorbiaceae; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007371:Interferon-gamma; D008070:Lipopolysaccharides; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis
D008070:Lipopolysaccharides; D010936:Plant Extracts; D012333:RNA, Messenger; D009569:Nitric Oxide; D007371:Interferon-gamma; D010696:Phloroglucinol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse