Bromelain improves decrease in defecation in postoperative rats: modulation of colonic gene expression of inducible nitric oxide synthase.

Ileus continues to be a common consequence of abdominal surgery, causing significant patient discomfort and often leading to more serious problems. The therapy available is limited, hence, ileus remains an important clinical problem. Activation of inducible nitric oxide synthase (iNOS) directly modulates intestinal dysmotility after bowel manipulation and plays an essential role in initiating intestinal inflammation. Nuclear factor (NF)-kappaB is known to be a critical component of iNOS gene transcriptional activation in response to inflammatory stimuli. Bromelain is a crude extract from the pineapple stem, which is sold as a nutritional supplement to "promote digestive health" and as an anti-inflammatory medication in some developed countries. Here, we have found that oral administration of bromelain improves decrease in defecation in abdominal postoperative rats. Results showed that bromelain increased the wet weight, dry weight, water content and number of fecal pellets in laparotomized plus mechanically manipulated rats, suggesting improvement of postoperative ileus. Furthermore, bromelain treatment inhibited overexpressed iNOS mRNA and restored down-regulated inhibitor kappaBalpha mRNA in the colon of the postoperative rats. From the in vitro experiments, bromelain inhibits lipopolysaccharide (LPS)-induced nitrite overproduction in macrophage cell lines and LPS-induced NF-kappaB luciferase reporter gene expression in RAW264.7 macrophages transfected with NF-kappaB luciferase reporter gene. Thus, our findings suggest that bromelain improves decrease in defecation in postoperative rats, at least in part, by inhibiting colonic iNOS overexpression via NF-kappaB pathway. Our data indicates that bromelain may benefit patients with postoperative ileus.