Supercritical fluid carbon dioxide extract of <i>Alpinia oxyphylla</i> ameliorates dextran sulfate sodium-induced intestinal barrier damage in mice

Abstract

Purpose: Inflammation and oxidative stress are the leading causes of intestinal barrier dysfunction and a wide range of diseases. The  purpose of this study was to explore the protective effect and elucidate potential mechanisms of supercritical carbon dioxide extract from  Alpinia oxyphylla Miq. (AOE) on intestinal inflammation. Methods: The AOE was extracted by supercritical carbon dioxide extraction and its components were determined. Cytotoxicity of the  extract (0.05 to 20μg/mL) was determined on Caco-2 cells. In vitro assessment of whether AOE protected against LPS-induced intestinal  barrier dysfunction was done on Caco-2 cells pretreated with non-cytotoxic concentrations (0.5μg/mL and 1 μg/mL) of the extract. Experimental colitis of mouse model was induced by drinking water containing 3% dextran sulfate sodium (DSS). The intestinal  permeability was assessed by TEER and fluorescein isothiocyanate conjugated dextran (FITC). Pathological evidence and possible  mechanism were verified by tissue staining and molecular methods including quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Results: TEER and FITC testing indicated that AOE pretreatment significantly improved intestinal barrier hemostasis  (p<0.05). Furthermore, AOE pretreatment counteracted DSS-induced upregulation of pro-inflammatory cytokines and oxidative stress  (p<0.05). Lastly, two crucial signal pathways regarding hemostasis of intestinal barrier, NF-κB and NOX1-LCN2, were significantly  attenuated upon AOE pretreatment (p<0.05). Conclusion: This study sheds lights on the protective effect of AOE for intestinal hemostasis  and supports the development of AOE-based intestinal protective agents.