title: Anti-inflammatory effects of sulfuretin from Rhus verniciflua Stokes via the induction of heme oxygenase-1 expression in murine macrophages.
abstract: Rhus verniciflua Stokes (Anacardiaceae) has traditionally been used as an ingredient in East Asian medicines used to treat oxidative damage and cancer. Sulfuretin is one of the major flavonoid components isolated from R. verniciflua. In the present study, we isolated sulfuretin from R. verniciflua and demonstrated that sulfuretin inhibited inducible nitric oxide synthase (iNOS) protein and mRNA expression, reduced iNOS-derived NO, suppressed COX-2 protein and mRNA expression, and reduced COX-derived PGE(2) production in lipopolysaccharide (LPS)-stimulated RAW264.7 and murine peritoneal macrophages. Similarly, sulfuretin reduced tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) production. In addition, sulfuretin suppressed the phosphorylation and degradation of I kappaB-alpha as well as the nuclear translocation of p65 by the stimulation of LPS in RAW264.7 macrophages. Furthermore sulfuretin induced heme oxygenase (HO)-1 expression through nuclear translocation of nuclear factor E2-related factor 2 (Nrf)2 and increased heme oxygenase (HO) activity in RAW264.7 macrophages. The effects of sulfuretin on LPS-induced NO, PGE(2), TNF-alpha, and IL-1 beta production were partially reversed by the HO-1 inhibitor, tin protoporphyrin (SnPP). Therefore, it is suggested that sulfuretin-induced HO-1 expression plays a role of the resulting anti-inflammatory effects in macrophages. This indicated that the anti-inflammatory effects of sulfuretin in macrophages might be exerted through a novel mechanism that involves HO-1 expression.
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Dong-Sung
authors.initials: DS
authors.lastname: Lee
authors.forename: Gil-Saeng
authors.initials: GS
authors.lastname: Jeong
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Hyun
authors.initials: H
authors.lastname: Park
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000276:immunology; D027926:Anacardiaceae / Q000276:immunology; D000818:Animals; D001572:Benzofurans / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008518:Medicine, East Asian Traditional; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
chemical_list: D001572:Benzofurans; D005419:Flavonoids; D053583:Interleukin-1beta; D051267:NF-E2-Related Factor 2; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051547:Heme Oxygenase-1; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone; C054989:sulfuretin