Zerumbone ameliorates the inflammatory response and organ damage in severe acute pancreatitis via the ROS/NF-κB pathway

Abstract

Abstract Objective The aim of the current study was to determine the mechanism by which Zerumbone (ZER) ameliorates inflammation and organ damage in a rat model of severe acute pancreatitis (SAP). Methods Different concentrations of ZER (10, 20 and 40 mg/kg) were administered by femoral vein puncture 30 min prior to establishment of the SAP model. Hematoxylin and eosin (H&E) staining was used to assess pathological changes in the pancreatic tissue of SAP-induced rats. The lung wet/dry (W/D) ratio was assessed and serum levels of amylase (AMY), alanine aminotransferase (ALT), creatinine (Cr), aspartate aminotransferase (AST) and phospholipase A2 (PLA2) were measured. Western blot analysis was used to examine changes in the expression of ROS/NF-κB pathway-associated proteins. Results SAP was confirmed by significant histopathological damage to the pancreas. ZER (10, 20 and 40 mg/kg) was found to alleviate pancreatitis and decrease ascites volume, lung W/D ratio, pancreatic pathology score, oxidative stress and inflammatory damage. High concentrations (20 and 40 mg/kg) of ZER were shown to increase levels of hepatorenal toxicity. In contrast, 10 mg/kg ZER was found to attenuate liver enzyme levels, reduce pathological damage to the liver, and protect against extrapancreatic organ damage to the liver in SAP-induced rats. Moreover, ZER showed no significant side effects in normal rats. Finally, we demonstrated that ZER mediated its anti-inflammatory effects on SAP through the ROS/NF-κB signaling pathway. Conclusion ZER alleviated SAP-induced oxidative stress and inflammatory injury via the ROS/NF-κB pathway, and had a protective effect on lung injury and liver damage.