Resveratrol: Efecto protector mediado por NOX1/SIRT1 para restaurar la integridad intestinal en la sepsis

One serious consequence of sepsis that has a direct impact on patient outcomes is intestinal barrier disruption brought on by sepsis. Although the polyphenolic molecule resveratrol (RE) is well-known for its anti-inflammatory and antioxidant properties, it is unknown how it affects the NADPH oxidase 1 (NOX1)/sirtuin 1 (SIRT1) pathway and against intestinal barrier failure by sepsis.

This work adopted a lipopolysaccharide (LPS)-treated Caco-2 cell and sepsis mice model (cecal ligation and puncture) to assess the protective effects of RE. We employed quantitative reverse transcription PCR, enzyme-linked immunosorbent assay, histological analysis, immunohistochemistry, and Western blot to assess survival rates, inflammatory cytokine levels, autophagy markers, and intestinal barrier function. The role of NOX1 and SIRT1 in RE-mediated protection was explored through NOX1 overexpression and related molecular analyses.

RE significantly improved survival rates in sepsis mice, reduced inflammatory cytokines, and restored intestinal barrier function. RE reversed the increase of NOX1 and the decrease of SIRT1 observed in sepsis. Histological analysis showed that RE protected the intestinal structure, maintained the expression of tight junction proteins, and alleviated intestinal damage. In LPS-treated Caco-2 cells, RE inhibited inflammation, autophagy suppression, and reactive oxygen species (ROS) production. NOX1 overexpression partially reversed the protective effects of RE.

By modifying the NOX1/SIRT1 signaling pathway, RE guards against intestinal barrier failure by sepsis. These results underline the critical involvement of the NOX1/SIRT1 pathway in autophagy and inflammation control and imply that RE may be a viable treatment approach for intestinal damage associated with sepsis.