Tectochrysin ameliorates dextran sulfate sodium-induced chronic colitis by regulating the intestinal flora and inflammatory responses

Abstract

Tectochrysin (TEC) is a natural flavonoid with anti-inflammatory, antioxidant, antitumor, and wound-healing activity. However, little is known about the therapeutic effects of TEC on inflammatory bowel disease (IBD). This study investigated the anti-inflammatory effect of TEC on IBD. Mice with dextran sulfate sodium (DSS)-induced chronic colitis served as an in vivo model of IBD. Lipopolysaccharide (LPS)-stimulated J774A.1 macrophages and mouse bone marrow-derived macrophages (BMDMs) served as in vitro models of inflammation. In vivo, 0.5% (w/w) TEC ameliorated DSS-induced colitis in mice by decreasing lipocalin-2 levels, disease activity index, colon shorten, weight loss, histological scores, and the apoptosis of colonic mucosal cells; it improved intestinal barrier function by increasing the expression of ZO-1 and occludin, decreasing the Th17/Treg ratio, and reducing the protein expression of NLRP3 and caspase-1 in the colon. Moreover, TEC decreased inflammation by reducing the serum levels of pro-inflammatory cytokines IFN-γ, IL-1β, G-CSF, IL-6, IL-8, iNOS, and TNF-α and increasing the levels of anti-inflammatory cytokines Bcl-2 and IL-10. TEC increased the relative abundance of the beneficial bacteria norank_f_Muribaculaceae in the mouse intestine. In vitro, 500 ng/mL TEC reduced oxidative stress by decreasing LPS-induced mitochondrial ROS production in BMDMs. TEC alleviated the increased levels of IL-1β, IL-6, and TNF-α and increased IL-10 levels in the culture supernatant of LPS-stimulated J774A.1 macrophages and BMDMs. These results indicate that TEC has a protective effect on DSS-induced chronic colitis by inhibiting inflammation, improving intestinal barrier function, and regulating intestinal microbial composition. Therefore, TEC has a high potential to treat IBD.