BACKGROUND: Bromelain, a mixture of proteolytic enzymes typically derived from pineapple stem, decreases production of proinflammatory cytokines and leukocyte homing to sites of inflammation. We previously showed that short-term oral treatment with bromelain purified from pineapple stem decreased the severity of colonic inflammation in C57BL/6 Il10(-/-) mice with chronic colitis. Since fresh pineapple fruit contains similar bromelain enzymes but at different proportions, this study aimed to determine whether long-term dietary supplementation with pineapple (supplied as juice) could decrease colon inflammation and neoplasia in Il10(-/-) mice with chronic colitis as compared with bromelain derived from stem. METHODS: Colitis was triggered in Il10(-/-) mice by exposure to the non-steroidal anti-inflammatory drug piroxicam. Mice with colitis were supplemented with fresh vs. boiled pineapple juice or bromelain purified from stem for up to 6 months. RESULTS: Experimental mice readily consumed fresh pineapple juice at a level that generated mean stool proteolytic activities equivalent to 14 mg bromelain purified from stem, while control mice received boiled juice with inactive enzymes. Survival was increased in the group supplemented with fresh rather than boiled juice (P = 0.01). Mice that received fresh juice also had decreased histologic colon inflammation scores and a lower incidence of inflammation-associated colonic neoplasia (35% versus 66%; P < 0.02), with fewer neoplastic lesions/colon (P = 0.05). Flow cytometric analysis of murine splenocytes exposed to fresh pineapple juice in vitro demonstrated proteolytic removal of cell surface molecules that can affect leukocyte trafficking and activation. CONCLUSIONS: These results demonstrate that long-term dietary supplementation with fresh or unpasteurized frozen pineapple juice with proteolytically active bromelain enzymes is safe and decreases inflammation severity and the incidence and multiplicity of inflammation-associated colonic neoplasia in this commonly used murine model of inflammatory bowel disease.
BACKGROUND: Bromelain, a mixture of proteolytic enzymes typically derived from pineapple stem, decreases production of proinflammatory cytokines and leukocyte homing to sites of inflammation. We previously showed that short-term oral treatment with bromelain purified from pineapple stem decreased the severity of colonic inflammation in C57BL/6 Il10(-/-) mice with chronic colitis. Since fresh pineapple fruit contains similar bromelain enzymes but at different proportions, this study aimed to determine whether long-term dietary supplementation with pineapple (supplied as juice) could decrease colon inflammation and neoplasia in Il10(-/-) mice with chronic colitis as compared with bromelain derived from stem. METHODS:Colitis was triggered in Il10(-/-) mice by exposure to the non-steroidal anti-inflammatory drug piroxicam. Mice with colitis were supplemented with fresh vs. boiled pineapplejuice or bromelain purified from stem for up to 6 months. RESULTS: Experimental mice readily consumed fresh pineapplejuice at a level that generated mean stool proteolytic activities equivalent to 14 mg bromelain purified from stem, while control mice received boiled juice with inactive enzymes. Survival was increased in the group supplemented with fresh rather than boiled juice (P = 0.01). Mice that received fresh juice also had decreased histologic colon inflammation scores and a lower incidence of inflammation-associated colonic neoplasia (35% versus 66%; P < 0.02), with fewer neoplastic lesions/colon (P = 0.05). Flow cytometric analysis of murine splenocytes exposed to fresh pineapplejuice in vitro demonstrated proteolytic removal of cell surface molecules that can affect leukocyte trafficking and activation. CONCLUSIONS: These results demonstrate that long-term dietary supplementation with fresh or unpasteurized frozen pineapplejuice with proteolytically active bromelain enzymes is safe and decreases inflammation severity and the incidence and multiplicity of inflammation-associated colonic neoplasia in this commonly used murine model of inflammatory bowel disease.
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