Nobiletin acts anti-inflammatory on murine IL-10−/− colitis and human intestinal fibroblasts

Yvonne Hagenlocher, Sonja Gommeringer, Anna Held, Katharina Feilhauer, Jörg Köninger, Stephan C. Bischoff, Axel Lorentz

Inflammatory bowel disease (IBD) shows increasing prevalence over the last years. We propose that anti-inflammatory plant substances could be used as additional or alternative agents with good compliance in prevention and/or therapy of IBD and its complication intestinal fibrosis. We could recently show that the citrus flavonoid nobiletin acts anti-inflammatory on activation of intestinal mast cells. Here, we analysed the effects of nobiletin on inflammation and fibrosis in IL-10-/-colitis. IL-10-/-and wild-type (WT) mice were orally treated with/without vehicle or nobiletin. Clinical symptoms of colitis and disease activity index (DAI) were assessed, and colon tissue was analysed for tissue damage, cellular infiltration, bowel wall thickness, mast cell number and degranulation, as well as collagen deposition as marker for fibrosis. Human intestinal fibroblasts (hiFB) were treated with nobiletin and the expression of collagen and pro-inflammatory cytokines was measured. Nobiletin treatment of IL-10-/-mice resulted in a reduction of clinical colitis symptoms and a longer survival time. In addition, histological scores of colitis were reduced compared to control groups. Mast cell number and degranulation was lower in nobiletin treated IL-10-/-mice, and correlated positively with DAI. As well, fibrotic marker of collagen deposition was reduced by nobiletin. In hiFB, the expression of collagen as well as of pro-inflammatory cytokines IL-6, TNF and CCL2 was down-regulated by nobiletin treatment. Nobiletin decreases inflammatory symptoms and markers in murine colitis as well as fibrotic collagen deposition and expression. Thus, nobiletin could be a potential new agent in therapy of chronic colitis.