Objective: The present study aimed to evaluate the protective effects of scopoletin (SC) on cerulein-induced acute pancreatitis (AP) and associated lung injury in mice.
Methods: Acute pancreatitis was induced in male Swiss mice by 6 consecutive hourly intraperitoneal injections of cerulein (50 μg/kg). Scopoletin was administered 1 hour (intraperitoneal, 10 mg/kg) after the first cerulein injection.
Results: Administration of SC attenuated the severity of AP and associated lung injury as shown by histology, reduced myeloperoxidase, and serum amylase activity. Further, the anti-inflammatory effect of SC was associated with a reduction of pancreatic and pulmonary proinflammatory cytokines (interleukin 1β and tumor necrosis factor α) and hydrogen sulfide. Moreover, SC inhibited cerulein-induced nuclear factor κB activation in both pancreas and lung. Also, SC treatment further enhances the beneficial effect by reducing cerulein-induced mast cell activation as shown by reduced monocyte chemoattractant protein 1, interleukin 33, and preprotachykinin A expression (encodes neuropeptide substance P) in the pancreas and lungs.
Conclusions: The present findings show for the first time that in AP SC may exhibit an anti-inflammatory effect by down-regulating substance P and hydrogen sulfide signaling via nuclear factor κB pathway.