Berberine decreases S100B generation to regulate gut vascular barrier permeability in mice with burn injury

Context: Berberine (BBR) can regulate enteric glial cells (EGCs) and the gut vascular barrier (GVB).Objective: To explore whether BBR regulates GVB permeability via the S100B pathway.Materials and methods: GVB hyperpermeability in C57BL/6J mice was induced by burns or S100B enema. BBR (25 or 50 mg/kg/d, 3 d) was gavaged preburn. S100B monoclonal antibody (S100BmAb) was i.v. injected postburn. Mouse intestinal microvascular endothelial cells (MIMECs) were treated with S100B, S100B plus BBR, or Z-IETD-FMK. GVB permeability was assayed by FITC-dextran, S100B by ELISA, Caspase-8, β-catenin, occludin and PV-1 by immunoblot.Results: Burns elevated S100B in serum and in colonic mucosa to a peak (147.00 ± 4.95 ng/mL and 160.30 ± 8.50 ng/mg, respectively) at 36 h postburn, but BBR decreased burns-induced S100B in serum (126.20 ± 6.30 or 90.60 ± 3.78 ng/mL) and in mucosa (125.80 ± 12.40 or 91.20 ± 8.54 ng/mg). Burns raised GVB permeability (serum FITC-dextran 111.40 ± 8.56 pg/mL) at 48 h postburn, but BBR reduced GVB permeability (serum FITC-dextran 89.20 ± 6.98 or 68.60 ± 5.50 ng/mL). S100B enema (1 μM) aggravated burns-raised GVB permeability (142.80 ± 8.07 pg/mL) and PV-1, but the effect of S100B was antagonized by BBR. Z-IETD-FMK (5 μM) increased S100B-induced permeability to FITC-dextran (205.80 ± 9.70 to 263.80 ± 11.04 AUs) while reducing β-catenin in MIMECs. BBR (5 μM) reduced S100B-induced permeability (104.20 ± 9.65 AUs) and increased Caspase-8, β-catenin and occludin.Discussion and conclusion: BBR decreases burns-induced GVB hyperpermeability via modulating S100B/Caspase-8/β-catenin pathway and may involve EGCs.

Enteric glial cells; caspase-8; occludin; β-catenin.