Protective Effects of Lithospermum erythrorhizon Against Cerulein-Induced Acute Pancreatitis

The incidence of acute pancreatitis (AP), a sudden inflammatory condition of the pancreas, has been increasing in recent years.1 In most patients with AP, the disease is mild and self-limited; however, approximately 25% of the patients with AP have a severe course, and approximately 30% of those with acute necrotizing pancreatitis die.2,3 In general, acinar cell response to the activation of trypsinogen in the pancreas is believed to play a role in initiating AP. Acinar cell responses leads to the recruitment of inflammatory cells and generation of inflammatory mediators.4–6 Despite the clinical importance of AP, specific and effective therapies are lacking because the pathogenesis of the disease is not yet fully understood. To verify the pathophysiology of AP, many cellular and animal models of AP have been used.7 Among them, cerulein-induced pancreatitis is one of the best characterized and widely used experimental models.8 The administration of cerulein, a cholecystokinin analog, takes advantage of a supramaximal induction of digestive enzyme secretion, which leads to premature enzyme activation, pancreatic cell injury, interstitial edema, and infiltration of inflammatory cells into the pancreas.8,9 Lithospermum erythrorhizon (LE) has long been used as a traditional Asian medicine for the treatment of rash, eczema, ulcers, and constipation.10 Recent in vitro and in vivo studies have shown beneficial pharmacological effects of LE root extract, such as anti-inflammatory and anticancer activity.11,12 However, the protective activities of LE on cerulein-induced AP have not yet been reported. Therefore, our aim was to investigate the effect of LE on cerulein-induced AP and the underlying transduction mechanisms involved. To gain a better insight of the effects of LE, we investigated its activities of in vivo experimental pancreatitis as well as in vitro in isolated pancreatic acinar cells.