Deoxyschisandrin inhibits H2O2-induced apoptotic cell death in intestinal epithelial cells through nuclear factor-κB

Oxidative stress is a pathogenesis for a typical inflammatory intestinal disease known as ulcerative colitis (UC) characterized by erosion and mucosal ulceration. For the treatment of UC, many kinds of traditional Asian medical plants have been used. Schisandra chinensis fruits (SC) are known to possess anti-ulcer, anti-hepatotoxic and anti-neurotoxic activity. However, its mechanism is still unknown. In the present study, we investigated the cytoprotective effect of deoxyschisandrin, a lignan compound comprised of SC fruits, on H 2 O 2 -induced apoptotic cell death in human intestinal epithelial cells (HCT116). In flow cytometry assay using Annexin V and propidium iodide, deoxyschisandrin inhibited H 2 O 2 -induced apoptotic cell death. To further evaluate the apoptotic signaling by H 2 O 2 , we detected caspase-3 activation using cleavage of pro-caspase-3. Deoxyschisandrin inhibited H 2 O 2 -induced caspase-3 activation by blocking cleavage of pro-caspase-3. Furthermore, it has been reported that oxidative stress by H 2 O 2 induces an activation of nuclear factor-κB (NF-κB). In our results, H 2 O 2 stimulated the degradation of IκBα, inhibitor of NF-κB, in a concentration-dependent manner. On the contrary, deoxyschisandrin inhibited H 2 O 2 -stimulated degradation of IκBα and activation of NF-κB by blocking translocation of NF-κB to the nucleus. Therefore, we suggest that deoxyschisandrin inhibits H 2 O 2 -induced apoptotic cell death.