Fisetin attenuates cerulein-induced acute pancreatitis through down regulation of JNK and NF-κB signaling pathways.

Acute pancreatitis (AP) is a complicated disease which is largely undiscovered. Fisetin, a natural flavonoid from fruits and vegetables, has been shown to have anti-inflammatory, antioxidant, and anti-cancer activities in various disease models. However, the effects of fisetin on AP have not been determined. Pre- and post- treatment of mice with fisetin reduced the severity of AP and pancreatitis-associated lung injury and inhibited several biochemical parameters (pancreatic weight to body weight ratio, amylase, lipase, and myeloperoxidase activity) and production of inflammatory cytokines. In pancreatic acinar cells, fisetin also inhibited cell death and production of inflammatory cytokines. In addition, fisetin inhibited activation of c-Jun NH2-terminal kinase (JNK) and nuclear factor (NF)-κB in vivo and in vitro. In conclusion, these results suggest that fisetin exhibits anti-inflammatory effect on AP and could be a beneficial agent in the treatment of AP and its pulmonary complications.

Scolopendra subspinipes mutilans protected the cerulein-induced 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-1ß. 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.

Protective effects of alpha-pinene in mice with cerulein-induced acute pancreatitis.

AIMS: Acute pancreatitis (AP) is a complicated inflammatory disease that has an unknown underlying pathogenesis. Because alpha-pinene can modulate inflammation, we examined whether alpha-pinene plays a role in AP. MAIN METHODS: Alpha-pinene was administered intraperitoneally 1h prior to the first injection of cerulein. Once AP developed, cerulein, a stable cholecystokinin analog, was injected hourly over a 6-h period. Blood samples were taken 6h later to determine serum amylase and lipase levels. The pancreas and lungs were rapidly removed for morphological examination, myeloperoxidase assay, and real-time reverse transcription polymerase chain reaction. We also isolated the pancreatic acinar cells using a collagenase solution. Cell viability, and cytokine productions were measured in pancreatic acini. KEY FINDINGS: Intraperitoneal administration of alpha-pinene reduced the pancreatic weight (PW) to body weight (BW) ratio and the serum levels of amylase and lipase. Alpha-pinene treatment also reduced histological damage and myeloperoxidase activity in the pancreas and lungs. Furthermore, alpha-pinene pretreatment reduced the production of pancreatic tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 during cerulein-induced AP. In vitro, alpha-pinene inhibited cerulein-induced cell death and cytokine production in isolated cerulein-treated pancreatic acinar cells. SIGNIFICANCE: These findings suggest that alpha-pinene has an anti-inflammatory effect during cerulein-induced AP.