Prostaglandin E(2) production and induction of prostaglandin endoperoxide synthase-2 is inhibited in a murine macrophage-like cell line, RAW 264.7, by Mallotus japonicus phloroglucinol derivatives.
An aqueous acetone extract obtained from the pericarps of Mallotus japonicus (MJE) was observed to inhibit prostaglandin (PG) E(2) production in a lipopolysaccharide (LPS)-activated murine macrophage-like cell line, RAW 264.7. Six phloroglucinol derivatives isolated from MJE exhibited inhibitory activity against PGE(2) production. Among these phloroglucinol derivatives, isomallotochromanol showed the strongest inhibitory activity, with an IC(50) of 1.0 microM. MJE and its phloroglucinol derivatives did not effect the enzyme activity of either prostaglandin endoperoxide synthase (PGHS)-1 or PGHS-2. However, induction of PGHS-2 in LPS-activated macrophages was inhibited by MJE and its phloroglucinol derivatives, whereas the level of PGHS-1 protein was not affected. Moreover, RT-PCR analysis showed that MJE and its phloroglucinol derivatives significantly suppressed PGHS-2 mRNA expression. Therefore, the observed inhibition of PGHS-2 induction by MJE and its phloroglucinol derivatives was likely due to a suppression of PGHS-2 mRNA expression. These results suggest that MJE and its phloroglucinol derivatives have the pharmacological ability to suppress PGE(2) production by activated macrophages.
Ishii
Rie
R
Saitama Institute of Public Health, 639-1 Kamiokubo Saitama, Japan.
Horie
Masakazu
M
Saito
Koichi
K
Arisawa
Munehisa
M
Kitanaka
Susumu
S
D000818:Animals; D002460:Cell Line; D015232:Dinoprostone / Q000096:biosynthesis*; D004790:Enzyme Induction; D019665:Euphorbiaceae / Q000737:chemistry*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D010696:Phloroglucinol / Q000031:analogs & derivatives / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis
D010936:Plant Extracts; D012333:RNA, Messenger; D010696:Phloroglucinol; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone