Brazilian propolis extract reduces intestinal barrier defects and inflammation in a colitic mouse model

Abstract

Brazilian propolis is rich in cinnamic acid derivatives and reportedly reduces intestinal inflammation in rodents; however, the underlying mechanisms remain unclear. We hypothesized that the regulation of tight junction (TJ) barrier, Th17 cell differentiation, and/or, macrophage activation by cinnamic acid derivatives were involved in the propolis-mediated anti-inflammatory effect. Mice were orally administered 2% dextran sodium sulfate (DSS) in combination with either the feeding control or a diet containing 0.3% ethanol extract of Brazilian propolis for 9 days. DSS administration induced acute colitis in mice, whereas the propolis extract mitigated DSS-induced weight loss; colon shortening; increased plasma levels of lipopolysaccharide-binding protein; reduced expression of TJ proteins, such as zonula occludens, junctional adhesion molecule-A, occludin, and claudins; and increased expression of inflammatory cytokines, such as tumor necrosis factor (TNF) α, interleukin (IL) 6, and IL-17a. Cinnamic acid derivatives, such as artepillin C and caffeic acid phenethyl ester, present in the propolis extract suppressed the IL-17 production from cultured murine splenocytes through decreased retinoic acid-related orphan receptor gT expression. Baccharin, drupanin, and culifolin, which are also present in Brazilian propolis, reduced the TNF-α and/or IL-6 production by suppressing inflammatory signaling in murine RAW 264.7 macrophages. Taken together, the regulation of Th17 differentiation and macrophage activation by cinnamic acid derivatives, at least in part, contribute to the anti-inflammatory effect mediated by Brazilian propolis.