Emodin alleviates intestinal mucosal injury in rats with severe acute pancreatitis via the caspase-1 inhibition.

BACKGROUND: Emodin, a traditional Chinese medicine, has a therapeutic effect on severe acute pancreatitis (SAP), whereas the underlying mechanism is still unclear. Studies showed that the intestinal mucosa impairment, and subsequent release of endotoxin and proinflammatory cytokines such as IL-1ß, which further leads to the dysfunction of multiple organs, is the potentially lethal mechanism of SAP. Caspase-1, an IL-1ß-converting enzyme, plays an important role in this cytokine cascade process. Investigation of the effect of emodin on regulating the caspase-1 expression and the release proinflammatory cytokines will help to reveal mechanism of emodin in treating SAP. METHODS: Eighty Sprague-Dawley rats were randomly divided into four groups (n=20 each group): SAP, sham-operated (SO), emodin-treated (EM) and caspase-1 inhibitor-treated (ICE-I) groups. SAP was induced by retrograde infusion of 3.5% sodium taurocholate into the pancreatic duct. Emodin and caspase-1 inhibitor were given 30 minutes before and 12 hours after SAP induction. Serum levels of IL-1ß, IL-18 and endotoxin, histopathological alteration of pancreas tissues, intestinal mucosa, and the intestinal caspase-1 mRNA and protein expressions were assessed 24 hours after SAP induction. RESULTS: Rats in the SAP group had higher serum levels of IL-1ß and IL-18 (P<0.05), pancreatic and gut pathological scores (P<0.05), and caspase-1 mRNA and protein expressions (P<0.05) compared with the SO group. Compared with the SAP group, rats in the EM and ICE-I groups had lower IL-1ß and IL-18 levels (P<0.05), lower pancreatic and gut pathological scores (P<0.05), and decreased expression of intestine caspase-1 mRNA (P<0.05). Ultrastructural analysis by transmission electron microscopy found that rats in the SAP group had vaguer epithelial junctions, more disappeared intercellular joints, and more damaged intracellular organelles compared with those in the SO group or the EM and ICE-I groups. CONCLUSIONS: Emodin alleviated pancreatic and intestinal mucosa injury in experimental SAP. Its mechanism may partly be mediated by the inhibition of caspase-1 and its downstream inflammatory cytokines, including IL-1ß and IL-18. Our animal data may be applicable in clinical practice.

[Effects of emodin on cell apoptosis of intestinal mucosa and serum leptin in rats with severe acute pancreatitis].

OBJECTIVE: To explore the mechanisms of emodin in protecting intestinal mucosal barrier in rat with severe acute pancreatitis (SAP). METHODS: Sixty SD rats were randomly divided into three groups: sham-operation group, untreated group, and emodin group. SAP in rats of the untreated group and the emodin group was induced by retrograde pumping of 3.0% sodium cholate to the common bile duct. Specimens were obtained 24 hours after the severe acute pancreatitis was induced. Serum level of leptin, serum activity of amylase and plasma content of endotoxin were measured. Ileum mucosa from ileocecal junction was observed by light microscopy and electron microscopy to measure pathological and ultrastructural changes. Apoptosis of ileum mucosal cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method, and expression of Bax in ileum mucosal cells was measured by immunohistochemical method. RESULTS: Compared with the sham-operation group, there was significant increase in the levels of leptin, endotoxin, the activity of amylase, apoptosis index and Bax expression in the untreated group (P<0.01). Compared with the untreated group, the level of endotoxin, apoptotic index and Bax expression level in the emodin group were significantly reduced (P<0.01) and the leptin level was increased (P<0.05). More severe pathological changes appeared in the untreated group than in the sham-operation group under the light and electron microscopes; meanwhile less severe damage was observed in the emodin group as compared with the untreated group. CONCLUSION: Emodin can inhibit the apoptosis of intestinal mucosa cells and up-regulate the serum leptin content to protect the intestina1 barrier function and prevent the translocation of bacteria and endotoxin.