Protective effect of asiatic acid in an experimental cerulein-induced model of acute pancreatitis in mice

Asiatic acid (AA), a triterpenoid derived from the medicinal plant Centella asiatica, is considered to have anti-inflammatory, anti-fibrotic and anti-tumor effects, but its effects in acute pancreatitis (AP) are unknown. Our purpose of this study was to investigate the effects of AA in a mouse model of cerulein-induced pancreatitis. We evaluated AA in an experimental model of AP induced in mice by six hourly intraperitoneal injections of cerulein 50 mu g/kg. Mice were pretreated with vehicle or AA 50 mg/kg 2 h before the first cerulein injection. The severity of AP was evaluated histologically and by biochemistry, myeloperoxidase activity, proinflammatory cytokine production, and nuclear factor (NF)-kappa B activity. Administration of AA significantly reduced the severity of AP, and was associated with reduction of serum amylase and lipase levels, decreased pancreatic histological damage, and decreased myeloperoxidase activity. The serum levels and mRNA expression of interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)-alpha, and NF-kappa B activity were reduced. AA also significantly improved the in vitro viability of pancreatic acinar cells induced by cholecystokinin (CCK) and suppressed NF-kappa B activity. AA protected against experimental AP, possibly by reducing production of proinflammatory cytokines via suppression NF-kappa B activation.