Deoxyschisandrin inhibits H2O2-induced apoptotic cell death in intestinal epithelial cells through nuclear factor-kappaB.
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 H2O2-induced apoptotic cell death in human intestinal epithelial cells (HCT116). In flow cytometry assay using Annexin V and propidium iodide, deoxyschisandrin inhibited H2O2-induced apoptotic cell death. To further evaluate the apoptotic signaling by H2O2, we detected caspase-3 activation using cleavage of pro-caspase-3. Deoxyschisandrin inhibited H2O2-induced caspase-3 activation by blocking cleavage of pro-caspase-3. Furthermore, it has been reported that oxidative stress by H2O2 induces an activation of nuclear factor-kappaB (NF-kappaB). In our results, H2O2 stimulated the degradation of IkappaBalpha, inhibitor of NF-kappaB, in a concentration-dependent manner. On the contrary, deoxyschisandrin inhibited H2O2-stimulated degradation of IkappaBalpha and activation of NF-kappaB by blocking translocation of NF-kappaB to the nucleus. Therefore, we suggest that deoxyschisandrin inhibits H2O2-induced apoptotic cell death.
Gu
Bon-Hee
BH
Department of Immunology, Institute of Medical Sciences, Chonbuk National University Medical School, Jeonju, Jeonbuk, Korea.
Minh
Nguyen Van
NV
Lee
Sun-Hee
SH
Lim
Sung-Won
SW
Lee
Young-Mi
YM
Lee
Kang-Soo
KS
Kim
Dae-Ki
DK
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D034242:Cyclooctanes / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology*; D017705:Lignans / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D011083:Polycyclic Compounds / Q000494:pharmacology*
D034242:Cyclooctanes; D017705:Lignans; D016328:NF-kappa B; D016877:Oxidants; D011083:Polycyclic Compounds; C034734:schizandrin A; D006861:Hydrogen Peroxide