HMOC, a chrysin derivative, induces tolerogenic properties in lipopolysaccharide-stimulated dendritic cells.

Although we previously identified a new hydroxymethoxyl chrysin derivative (HMOC) using ionizing radiation, the anti-inflammatory mechanism of HMOC in dendritic cells remains unclear. In this study, we investigate the effects of HMOC on phenotypic and functional changes in activated bone marrow-derived dendritic cells (BMDCs). In lipopolysaccharide (LPS)-stimulated BMDCs, HMOC treatment inhibited pro-inflammatory cytokines (TNF-α, IL-12p70, and IL-1ß), surface molecules (CD80, CD86, MHC-I, and MHC-II), and antigen-presentation to MHC-I and II without a decrease in IL-10. Furthermore, HMOC increased indoleamine 2,3-dioxygenase-1 (IDO1) activity via activation of JNK and p38 signaling in the presence of LPS. Interestingly, LPS-stimulated DCs treated with HMOC inhibited the proliferation and activation of CD4+ and CD8+ T cells, as well as differentiation of CD4+ T cells into Th1-, Th2- and Th17 cells. In addition, LPS-stimulated DCs treated with HMOC induced an increase in CD4+CD25+Foxp3+ regulatory T cells (Tregs). Collectively, our results suggest that HMOC confers tolerogenic properties in BMDCs, which are responsible for inducing Th cell differentiation to Tregs. Our findings provide a better understanding of the anti-inflammatory mechanism of HMOC in DCs and may contribute to development of a valuable therapeutic candidate for atopic dermatitis.

A hydroxyethyl derivative of chrysin exhibits anti-inflammatory activity in dendritic cells and protective effects against dextran sodium salt-induced colitis in mice.

Inflammatory bowel disease (IBD) is a chronic disease that occurs in the intestinal tract. Phyto-ingredients have been evaluated for their ability to protect against IBD because of their anti-inflammatory activities. In our previous study, we identified a novel derivative of chrysin (HE-chrysin) using irradiation technology, which exhibited stronger anti-cancer activity in human colorectal cancer cells than the original chrysin. Here, to determine whether HE-chrysin is a new therapeutic candidate for IBD, we investigated the anti-inflammatory effects of HE-chrysin on bone marrow-derived dendritic cells (BMDCs) and dextran sodium salt (DSS)-induced colitis in mice. HE-chrysin more effectively inhibited BMDC maturation compared to chrysin, as demonstrated by the decreased levels of pro-inflammatory cytokines, surface molecules, antigen-presenting ability, and T cell proliferation/activation in lipopolysaccharide-stimulated BMDCs. These anti-inflammatory effects of HE-chrysin were regulated by mitogen-activated protein kinases and nuclear factor-κB. Furthermore, oral administration of HE-chrysin attenuated DSS-induced colitis symptoms and clinical signs in the mouse model. The protective effects of HE-chrysin treatment against colitis were mediated by decreasing Th1- and Th17-type cytokine levels. These results indicate that HE-chrysin is attractive candidate for IBD therapy.