Anti-inflammatory effects of sulfuretin from Rhus verniciflua Stokes via the induction of heme oxygenase-1 expression in murine macrophages

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 PGE2 production in lipopolysaccharide (LPS)-stimulated RAW264.7 and murine peritoneal macrophages. Similarly, sulfuretin reduced tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) production. In addition, sulfuretin suppressed the phosphorylation and degradation of IκB-α 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, PGE2, TNF-α, and IL-1β 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.