Sulforaphane Protects Pancreatic Acinar Cell Injury by Modulating Nrf2-Mediated Oxidative Stress and NLRP3 Inflammatory Pathway

Figure 5

A schematic representation of the modulatory effects of SFN on cellular oxidative and inflammatory pathways during AP. Cerulein induces oxidative stress and inflammation in primary acinar cells or mice with AP. Prophylactic treatment of SFN restored steady-state pancreatic levels of MDA and redox enzymes including GPx and SOD, which were dysregulated towards enhanced oxidative state during AP. Further mechanistic investigation revealed that SFN enhanced the expression of Nrf2 in pancreatic acinar cells and Nrf2-regulated genes including NQO1, HO-1, SOD1, and GPx critical in the pathogenesis of AP. Moreover, SFN selectively suppressed cerulein-induced activation of NLRP3 inflammasome in pancreatic acinar cells, in parallel with decreased NF-κB activity and reduced expressions of IL-1β, TNF-α, IL-6, and TGF-β. Together, SFN suppresses oxidative stress and inflammatory responses via Nrf2 and NLRP3 NF-κB pathways, respectively, thereby protecting AP.