Isoliquiritin alleviates sepsis-induced intestinal barrier dysfunction in mice potentially by promoting autophagy.

Intestinal barrier function protection is essential to ameliorate sepsis. Isoliquiritin (ILQ) is a natural compound with broad biological activities. However, whether ILQ attenuates sepsis-induced intestinal damage remains unclear. An LPS-induced sepsis mouse model was established. ILQ inhibited body weight loss in sepsis mice. ILQ enhanced mouse intestinal function, as evidenced by decreased serum LDH levels and increased citrulline levels. Alcian blue staining showed that ILQ increased goblet cells in sepsis mouse ileum. ILQ increased the MUC2 RNA levels and decreased the claudin-2 protein expression in the sepsis mouse ileum. We subsequently examined the ILQ effects on intestinal autophagy activity. ILQ reduced the p62 protein expression and increased the conversion of LC3BI to LC3BII in sepsis mouse ileum. The LC3 protein expression was reduced in sepsis mouse ileum. An LPS-stimulated Caco-2 cell model was established. ILQ enhanced the viability of LPS-stimulated Caco-2 cells, reduced the LDH activity in cell supernatants, and increased the MUC2 RNA levels. ILQ enhanced the cellular barrier of LPS-stimulated Caco-2 cells, as indicated by the reduction in claudin-2 protein and the increase in TEER. ILQ also promoted autophagy activity in LPS-stimulated Caco-2 cells. Rescue experiments showed that an autophagy inhibitor disrupts the protective effect of ILQ on the Caco-2 cell barrier and inhibits ILQ-promoted autophagy activity. ILQ promoted the expression of LC3BII following the addition of chloroquine in LPS-stimulated Caco-2 cells. In conclusion, ILQ alleviated intestinal dysfunction and promoted autophagy activity in sepsis mice ileum, and might enhance the barrier function of LPS-stimulated Caco-2 cells via autophagy.