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 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.
Highlights
Inflammatory bowel disease (IBD) encompasses two chronic intestinal diseases, Crohn's disease (CD) and ulcerative colitis (UC), which are characterized by recurrent flare of inflammation in the gastrointestinal tract (Podolsky, 2002; Elson et al, 2005)
We examined the inhibitory effects and mechanism of action of Grifola frondosa (GF) water extract (GFW) on intestinal inflammation by using in vitro bioassay model of inflammatory bowel disease (IBD) in which HT-29 cells were treated with TNF-α, and in vivo animal model of IBD, trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats
Administration of the rats with GFW or 5-aminosalicylic acid (5-ASA) (i.p. 100 mg/kg) significantly reversed the decrease of body weight and increase of colon weight associated with TNBSinduced colitis
Summary
Inflammatory bowel disease (IBD) encompasses two chronic intestinal diseases, Crohn's disease (CD) and ulcerative colitis (UC), which are characterized by recurrent flare of inflammation in the gastrointestinal tract (Podolsky, 2002; Elson et al, 2005). Upon stimulation with TNF-α, intestinal epithelium produces reactive oxygen species (ROS) through NAD(P)H oxidase (Nox) activation (Kim et al, 2007; Babu et al, 2008). Such TNF-α-induced ROS leads to activation of the transcription factor, NF-κB, which is a major regulator of inflammatory gene expression The important role of MCP-1 during intestinal inflammation has been demonstrated in recent studies in which markedly increased MCP-1 level is observed in the colon tissue of IBD patients (Reinecker et al, 1995). We examined the inhibitory effects and mechanism of action of GFW on intestinal inflammation by using in vitro bioassay model of IBD in which HT-29 cells were treated with TNF-α, and in vivo animal model of IBD, TNBS-induced colitis in rats
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