Scolopendra subspinipes mutilans protected the ceruleininduced acute pancreatitis by inhibiting high-mobility group box protein-1

AIM:To evaluate the inhibitory effects of Scolopendra subspinipes mutilans(SSM) on cerulein-induced acute pancreatitis(AP) in a mouse model.METHODS:SSM water extract(0.1,0.5,or 1 g/kg) was administrated intraperitoneally 1 h prior to the first injection of cerulein.Once AP developed,the stable cholecystokinin analogue,cerulein was injected hourly,over a 6 h period.Blood samples were taken 6 h later to determine serum amylase,lipase,and cytokine levels.The pancreas and lungs were rapidly removed for morphological examination,myeloperoxidase assay,and real-time reverse transcription polymerase chain reaction.To specify the role of SSM in pancreatitis,the pancreatic acinar cells were isolated using collagenase method.Then the cells were pre-treated with SSM,then stimulated with cerulein.The cell viability,cytokine productions and high-mobility group box protein-1(HMGB-1) were measured.Furthermore,the regulating mechanisms of SSM action were evaluated.RESULTS:The administration of SSM significantly attenuated the severity of pancreatitis and pancreatitis associated lung injury,as was shown by the reduction in pancreatic edema,neutrophil infiltration,vacuolization and necrosis.SSM treatment also reduced pancreatic weight/body weight ratio,serum amylase,lipase and cytokine levels,and mRNA expression of multiple inflammatory mediators such as tumor necrosis factor-α and interleukin-1β.In addition,treatment with SSM inhibited HMGB-1 expression in the pancreas during AP.In accordance with in vivo data,SSM inhibited the cerulein-induced acinar cell death,cytokine,and HMGB-1 release.SSM also inhibited the activation of c-Jun NH2-terminal kinase,p38 and nuclear factor(NF)-κB.CONCLUSION:These results suggest that SSM plays a protective role during the development of AP and pancreatitis associated lung injury via deactivating c-Jun NH2-terminal kinase,p38 and NF-κB.

Effect of biologically active fraction of Nardostachys jatamansi on cerulein-induced acute pancreatitis

AIM:To determine if the fraction of Nardostachys jatamansi(NJ) has the potential to ameliorate the severity of acute pancreatitis(AP).METHODS:Mice were administered the biologically active fraction of NJ,i.e.,the 4th fraction(NJ4),intraperitoneally,and then injected with the stable cholecystokinin analogue cerulein hourly for 6 h.Six hours after the last cerulein injection,the pancreas,lung,and blood were harvested for morphological examination,measurement of cytokine expression,and examination of neutrophil infiltration.RESULTS:NJ4 administration attenuated the severity of AP and lung injury associated with AP.It also reduced cytokine production and neutrophil infiltration and resulted in the in vivo up-regulation of heme oxygenase-1(HO-1).Furthermore,NJ4 and its biologically active fraction,NJ4-2 inhibited the cerulein-induced death of acinar cells by inducing HO-1 in isolated pancreatic acinar cells.CONCLUSION:These results suggest that NJ4 may be a candidate fraction offering protection in AP and NJ4 might ameliorate the severity of pancreatitis by inducing HO-1 expression.