Sulforaphane protects intestinal epithelial cells against lipopolysaccharide-induced injury by activating the AMPK/SIRT1/PGC-1ɑ pathway.

The naturally occurring isothiocyanate sulforaphane, found in vegetables, shows promising anti-inflammatory, anti-apoptosis, and anti-oxidative effects. Whether sulforaphane protects against lipopolysaccharide (LPS)-induced injury in intestinal epithelial cells is unclear. The present study examines the ability of sulforaphane to protect Caco-2 cultures from LPS-induced injury, as well as the mechanism involved. Caco-2 cells were incubated for 24 h with 1 μg/mL LPS and different concentrations of sulforaphane (0.1-10 μM). Then, various indicators of oxidative stress, inflammation, apoptosis, and intestinal permeability were assayed. Sulforaphane increased cell viability and reduced lactate dehydrogenase activity in LPS-treated Caco-2 cells in a concentration-dependent manner. Sulforaphane weakened LPS-induced increases in intestinal epithelial cell permeability and oxidative stress (based on assays of reactive oxygen species, DMA, and HO), and it increased levels of antioxidants (SOD, GPx, CAT and T-AOC). At the same time, sulforaphane weakened the ability of LPS to induce production of inflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α) and the pro-apoptotic caspases-3 and -9. Sulforaphane also upregulated p-AMPK, SIRT1, and PGC-1ɑ, whose inhibitors antagonized the compound's protective effects. Sulforaphane can protect intestinal epithelial cells against LPS-induced changes in intestinal permeability, oxidative stress, inflammation, and apoptosis. It appears to act by activating the AMPK/SIRT1/PGC-1ɑ pathway. The drug therefore shows potential for preventing LPS-induced intestinal injury.