American ginseng suppresses colitis through p53-mediated apoptosis of inflammatory cells. 2010

Yu Jin, and Anne B Hofseth, and Xiangli Cui, and Anthony J Windust, and Deepak Poudyal, and Alex A Chumanevich, and Lydia E Matesic, and Narendra P Singh, and Mitzi Nagarkatti, and Prakash S Nagarkatti, and Lorne J Hofseth
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.

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.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D008214 Lymphocytes White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS. Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D008297 Male Males
D008517 Phytotherapy Use of plants or herbs to treat diseases or to alleviate pain. Herb Therapy,Herbal Therapy
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D003092 Colitis Inflammation of the COLON section of the large intestine (INTESTINE, LARGE), usually with symptoms such as DIARRHEA (often with blood and mucus), ABDOMINAL PAIN, and FEVER. Colitides
D005894 Panax An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. Sometimes confused with Siberian ginseng (ELEUTHEROCOCCUS). Ginseng,Korean Ginseng,Korean Red Ginseng,Panax ginseng,Jen Shen,Ninjin,Renshen,Schinseng,Shinseng,Ginseng, Korean,Ginseng, Korean Red,Ginsengs,Jen Shens,Korean Ginsengs,Korean Red Ginsengs,Ninjins,Red Ginseng, Korean,Renshens,Schinsengs,Shen, Jen,Shinsengs
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016159 Tumor Suppressor Protein p53 Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER. p53 Tumor Suppressor Protein,Cellular Tumor Antigen p53,Oncoprotein p53,TP53 Protein,TRP53 Protein,p53 Antigen,pp53 Phosphoprotein,Phosphoprotein, pp53

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