Saucerneol D inhibits dendritic cell activation by inducing heme oxygenase-1, but not by directly inhibiting toll-like receptor 4 signaling

Abstract

Ethnopharmacological relevance Saururus chinensis is a medicinal plant used to treat jaundice, pneumonia, edema, fever, and several inflammatory diseases. Saucerneol D (SD), a lignan constituent of this plant, has antioxidant, anti-asthmatic, and anti-inflammatory activities. SD has been previously reported to inhibit the pro-inflammatory responses of RAW264.7 cells and primary mast cells. In this study, we investigated the effect of SD on the functions of dendritic cells (DCs). Materials and methods SD was isolated from methanol extract of the roots of S. chinensis. Bone marrow-derived DCs were used as target cells. The effects of SD on the following DC functions were examined: surface molecule expression, cytokine expression, migration, allogenic T cell activation, heme oxygenase-1 expression, and Toll-like receptor 4 signaling. Results In lipopolysaccharide (LPS)-treated DCs, SD inhibited the expression of cell surface molecules (MHC I/II, CD40, CD80, and CD86), the production of inflammatory mediators (nitric oxide, IL-12, IL-1β, and TNF-α), and allogenic T cell activation capacity. SD also inhibited DC migration toward MIP-3β by down-regulating CCR7 expression. SD attenuated LPS-induced activation of NF-κB and MAPK signaling in DCs, but did not directly inhibit kinase activities of IRAK1, IRAK4, TAK1, or IKKβ in enzymatic assays. SD did not inhibit LPS binding to myeloid differentiation protein-2, co-receptor of TLR4. SD increased the production of reactive oxygen species, Nrf-2, and heme oxygenase (HO)-1, which degrades the heme to immunosuppressive carbon monoxide and biliverdin, which may underlie the anti-inflammatory effects in SD-treated DCs. Conclusions Taken together, these data suggest that SD suppresses LPS-induced activation of DCs through the induction of HO-1, but not by directly affecting Toll-like receptor 4 signaling