Berberine reduces enteroglial-derived S100B production to alleviate gut vascular barrier damage

Abstract

Gut vascular barrier (GVB) controls the systemic dissemination of bacteria. Enteric glial cells (EGCs) in mucosa as a component of gut vascular unit can amplify inflammation via S100B. Berberine (BBR) is an alkaloid that can alleviate gut inflammation and regulate EGCs activity. In this study, we aimed to unravel the mechanism by which BBR inhibited EGCs-derived S100B generation to protect GVB. In vivo BBR was given via oral gavage to mice who were subjected to 40% total body surface area burns. In vitro BBR, S100B and caspase-8 inhibitor Z-IETD-FMK were used to treat mouse intestinal microvascular endothelial cells (MIMECs). The results showed that (1) BBR lowered serum S100B concentration and decreased S100B accumulation in colonic mucosa; (2) BBR and S100B monoclonal antibody (S100BmAb) lowered burn-induced GVB hyperpermeability; (3) BBR antagonized the effect of S100B enema on GVB permeability; (4) S100B and Z-IETD-FMK increased the permeability of MIMECs and reduced the expression of caspase-8, β-catenin, occludin and VE-cadherin in MIMECs, while these effects of S100B were effectively antagonized by BBR treatment; (5) Z-IETD-FMK inhibited β-catenin expression in MIMECs. Collectively, our findings showed that S100B accumulation in gut mucosa damaged GVB, and BBR treatment alleviated GVB damage via modulation of caspase-8/β-catenin signaling pathways.