Diallyl Disulfide Attenuates STAT3 and NF-κB Pathway Through PPAR-γ Activation in Cerulein-Induced Acute Pancreatitis and Associated Lung Injury in Mice

We have previously shown that diallyl disulfide (DADS) protects mice against cerulein-induced acute pancreatitis (AP) and associated lung injury. However, the molecular mechanisms underlying its effect and the components involved have not been studied. We hypothesized that DADS may reduce TNF-alpha, CSE expression, H2S production, STAT3, and NF-kappa B activation and induce SOCS3 expression through peroxisome proliferator-activated receptor gamma (PPAR-gamma) pathway in cerulein-induced mice. Male Swiss mice were treated with hourly intraperitoneal injections of cerulein (50 mu g/kg) for 6 h. Diallyl disulfide (200 mu g/kg) was administered in the presence or absence of PPAR-gamma antagonist GW9662 (0.3 mg/kg) (i.p) 1 h after the induction of AP. Our findings revealed that DADS blocked TNF-alpha, CSE expression, H2S production, and STAT3, and NF-kappa B activation was reversed by GW9662. Furthermore, GW9662 abrogated DADS-induced SOCS3 expression. The results show for the first that DADS-induced anti-inflammatory effect in acute pancreatitis is regulated through PPAR-gamma.

Automated summary

This study investigates the anti-inflammatory effect of diallyl disulfide (DADS) in acute pancreatitis and its molecular mechanisms. The results show that DADS can reduce the expression of inflammatory molecules and induce the expression of specific genes through the PPAR-γ pathway. This provides a new therapeutic strategy for the treatment of acute pancreatitis.