Grifola frondosa water extract alleviates intestinal inflammation by suppressing TNF-alpha production and its signaling.
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.
Lee
Jong Suk
JS
College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Korea.
Park
Su Young
SY
Thapa
Dinesh
D
Choi
Mi Kyoung
MK
Chung
Ill Min
IM
Park
Young Joon
YJ
Yong
Chul Soon
CS
Choi
Han Gon
HG
Kim
Jung Ae
JA
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002457:Cell Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D018920:Coculture Techniques; D003106:Colon / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D048691:Grifola; D019073:HT29 Cells; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013276:Stomach Ulcer; D014158:Transcription, Genetic / Q000187:drug effects; D014302:Trinitrobenzenesulfonic Acid / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D020298:U937 Cells; D015431:Weight Loss
C111835:CCL2 protein, human; D002457:Cell Extracts; D018932:Chemokine CCL2; D016209:Interleukin-8; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase