Exp Mol Med.  2010 Feb;42(2):143-154. 10.3858/emm.2010.42.2.016.

Grifola frondosa water extract alleviates intestinal inflammation by suppressing TNF-alpha production and its signaling

• Lee JS
• Park SY
• Thapa D
• Choi MK
• Chung IM
• Park YJ
• Yong CS
• Choi HG
• Kim JA

• KMID: 983987
• DOI: http://doi.org/10.3858/emm.2010.42.2.016

Abstract

TNF-alpha is a major cytokine involved in inflammatory bowel disease (IBD). In this study, water extract of Grifola frondosa (GFW) was evaluated for its protective effects against colon inflammation through the modulation of TNF-alpha action. In coculture of HT-29 human colon cancer cells with U937 human monocytic cells, TNF-alpha-induced monocyte adhesion to HT-29 cells was significantly suppressed by GFW (10, 50, 100 microg/ml). The reduced adhesion by GFW correlated with the suppressed expression of MCP-1 and IL-8, the major IBD-associated chemokines. In addition, treatment with GFW significantly suppressed TNF-alpha-induced reactive oxygen species production and NF-kappaB transcriptional activity in HT-29 cells. In differentiated U937 monocytic cells, LPS-induced TNF-alpha production, which is known to be mediated through NF-kappaB activation, was significantly suppressed by GFW. In an in vivo rat model of IBD, oral administration of GFW for 5 days (1 g/kg per day) significantly inhibited the trinitrobenzene sulfonic acid (TNBS)-induced weight loss, colon ulceration, myeloperoxidase activity, and TNF-alpha expression in the colon tissue. Moreover, the effect of GFW was similar to that of intra-peritoneal injection of 5-aminosalicylic acid (5-ASA), an active metabolite of sulfasalazine, commonly used drug for the treatment of IBD. The results suggest that GFW ameliorates colon inflammation by suppressing production of TNF-alpha as well as its signaling through NF-kappaB leading to the expression of inflammatory chemokines, MCP-1 and IL-8. Taken together, the results strongly suggest GFW is a valuable medicinal food for IBD treatment, and thus may be used as an alternative medicine for IBD.

Keyword

complementary therapies; Grifola; inflammatory bowel diseases; NF-kappaB; trinitrobenzenesulfonic acid; tumor necrosis factor-alpha

MeSH Terms

Animals
Cell Adhesion/drug effects/immunology
Cell Extracts/administration & dosage/*pharmacology
Chemokine CCL2/biosynthesis/genetics
Coculture Techniques
Colon/drug effects/*metabolism/pathology
Grifola
HT29 Cells
Humans
Inflammatory Bowel Diseases/chemically induced/*drug therapy/pathology/physiopathology
Interleukin-8/biosynthesis/genetics
Intestinal Mucosa/*drug effects/metabolism/pathology
Monocytes/*drug effects/metabolism/pathology
NF-kappa B/genetics/metabolism
Peroxidase/metabolism
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species/metabolism
Stomach Ulcer
Transcription, Genetic/drug effects
Trinitrobenzenesulfonic Acid/administration & dosage
Tumor Necrosis Factor-alpha/*biosynthesis/genetics
U937 Cells
Weight Loss