Lycorine attenuates lipopolysaccharide-induced inflammation and intestinal epithelial barrier dysfunction in Caco-2...

Lycorine (LYC) is an isoquinoline alkaloid known for its various biological effects like anti-viral and anti-inflammatory. The purpose of this research was to offer a reference for the clinical application of LYC in inflammatory bowel disease. The toxicity of LYC on Caco-2 cells was assessed utilizing CCK-8 assay and Lactate dehydrogenase (LDH) kit. Tunel staining and flow cytometry determined apoptosis and Elisa kits measured levels of inflammatory factors. Trans-endothelial electrical resistance (TEER) assay and FITC-dextran assay for Caco-2 cell permeability. Western blot assessed the levels of inflammation-related and stimulator of interferon genes (STING)/nuclear factor kappaB (NF-κB) pathway proteins. Caco-2 cell viability and LDH release were not impacted by LYC concentrations below 20μM and LYC (5, 10 and 20μM) attenuated inflammation and apoptosis in Caco-2 cells induced by lipopolysaccharide (LPS). LPS decreased TEER values and increased FITC-dextran levels and LYC ameliorated epithelial barrier dysfunction caused by LPS. LPS activated the STING/NF-κB pathway, which was hindered by LYC. The protective impact of LYC on Caco-2 cells was reduced by over expression STING. In conclusion, LYC reduced cell death and inflammation in Caco-2 cells and preserved the integrity of the epithelial barrier by hindering the STING/NF-κB pathway.