Sesquiterpene Lactone Lactucopicrin Boosts Apoptotic Cell Clearance by Colonic Epithelial Cells and Alleviates Colitis in Mice

Abstract

Boosting apoptotic cell clearance by phagocytes including colonic epithelial cells (CECs), a process named efferocytosis, inhibits colitis development. Lactucopicrin (LCP), one common bitter sesquiterpene lactone affluent in leafy vegetables possesses a significant antiinflammatory property. However, it remains unknown whether LCP could regulate CECs efferocytosis and colitis development in vivo. Methods and Results: LCP (0.25-1 µmol/L) does not appreciably change the efferocytic capacity of murine primary CECs to clear apoptotic CECs. Instead, LCP dose-dependently increases the efferocytic capacity of CECs treated with butyrate (But). This effect is reliant on efferocytic receptor brain-specific angiogenesis 1 (BAI1). Although LCP does not significantly affect BAI1 expression, it alters BAI1 distribution with an increase in lipid raft microdomains in plasma membrane, an effect responsible for the LCP effect on efferocytic capacity. Moreover, dietary supplementation with 0.012% wt/wt of LCP attenuates dextran sulfate sodium (DSS)-induced colitis in C57BL/6J mice, along with an increase in efferocytic capacity of CECs and fecal But content, a reduction in apoptotic cell accumulation and inflammation burden in colonic tissues. Conclusion: Dietary LCP could inhibit DSS-induced colitis in mice, likely through enhancing BAI1-mediated efferocytosis of CECs, thus providing a new candidate for the treatment of colitis.