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

Abstract

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.

Keywords:

• Enteric glial cells
• caspase-8
• occludin
• β-catenin

Disclosure statement

The authors declare that they have no conflicts of interest.

Data availability statement

The data used to support the findings of this study are available from the corresponding author upon request.

Additional information

Funding

This research was supported by the project of Medical Science and Technology Foundation of Guangdong Province [A2022453, A2021087], Special Fund for Science and Technology of Maoming City [2020KJZX010], and High-level Hospital Construction Research Project of Maoming People’s Hospital [ZX2020019].