American ginseng suppresses colitis through p53-mediated apoptosis of inflammatory cells.
Ulcerative colitis is a dynamic, chronic inflammatory condition associated with an increased colon cancer risk. Inflammatory cell apoptosis is a key mechanism regulating ulcerative colitis. American ginseng (AG) is a putative antioxidant that can suppress hyperactive immune cells. We have recently shown that AG can prevent and treat mouse colitis. Because p53 levels are elevated in inflammatory cells in both mouse and human colitis, we tested the hypothesis that AG protects from colitis by driving inflammatory cell apoptosis through a p53 mechanism. We used isogenic p53(+/+) and p53(-/-) inflammatory cell lines as well as primary CD4(+)/CD25(-) effector T cells from p53(+/+) and p53(-/-) mice to show that AG drives apoptosis in a p53-dependent manner. Moreover, we used a dextran sulfate sodium (DSS) model of colitis in C57BL/6 p53(+/+) and p53(-/-) mice to test whether the protective effect of AG against colitis is p53 dependent. Data indicate that AG induces apoptosis in p53(+/+) but not in isogenic p53(-/-) cells in vitro. In vivo, C57BL/6 p53(+/+) mice are responsive to the protective effects of AG against DSS-induced colitis, whereas AG fails to protect from colitis in p53(-/-) mice. Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling of inflammatory cells within the colonic mesenteric lymph nodes is elevated in p53(+/+) mice consuming DSS + AG but not in p53(-/-) mice consuming DSS + AG. Results are consistent with our in vitro data and with the hypothesis that AG drives inflammatory cell apoptosis in vivo, providing a mechanism by which AG protects from colitis in this DSS mouse model.
Jin
Yu
Y
Department of Biomedical and Pharmaceutical Sciences, South Carolina College of Pharmacy, 770 Sumter Street, Coker Life Sciences, University of South Carolina, Columbia, SC 29208, USA.
Hofseth
Anne B
AB
Cui
Xiangli
X
Windust
Anthony J
AJ
Poudyal
Deepak
D
Chumanevich
Alex A
AA
Matesic
Lydia E
LE
Singh
Narendra P
NP
Nagarkatti
Mitzi
M
Nagarkatti
Prakash S
PS
Hofseth
Lorne J
LJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003092:Colitis / Q000517:prevention & control*; D016264:Dextran Sulfate / Q000633:toxicity; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D005894:Panax; D008517:Phytotherapy; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D016264:Dextran Sulfate