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
micg/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.