Nobiletin acts anti-inflammatory on murine IL-10−/− colitis and human intestinal fibroblasts
- 307 Downloads
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.
KeywordsNobiletin Colitis Fibroblasts Fibrosis Inflammation Nutraceuticals
The authors thank Yvonne Soltow for excellent technical assistance.
Compliance with ethical standards
Surgery tissue specimen from patients undergoing bowel resection served for isolation of human fiboblasts. This study has been approved by the local ethics committee and has therefore been performed in accordance with the ethical standards.
All persons gave their informed consent prior to their inclusion in the study.
Conflict of interest
All authors declare no conflicts of interest.
- 1.M’Koma AE (2013) Inflammatory bowel disease: an expanding global health problem. Clin Med Insights Gastroenterol 6:33–47Google Scholar
- 12.Evans M, Sharma P, Guthrie N (2004) Bioavailability of citrus polymethoxylated flavones and their biological role in metabolic syndrome and hyperlipidemia. Readings Adv Pharmacokinet—Theory, Methods Appl, pp 267–85Google Scholar
- 17.Murakami A, Nakamura Y, Torikai K, Stress O, Promotion T, Tanaka T et al (2000) Inhibitory effect of citrus nobiletin on phorbol ester-induced skin inflammation, oxidative stress, and tumor promotion in mice. Cancer Res 60:5059–5066Google Scholar
- 28.Latella G, Sferra R, Speca S, Vetuschi A, Gaudio E (2013) Can we prevent, reduce or reverse intestinal fibrosis in IBD. Eur Rev Med Pharmacol Sci 17:1283–1304Google Scholar
- 35.Choi SY, Hwang JH, Ko HC, Park JG, Kim SJ (2007) Nobiletin from citrus peel inhibits the DNA-binding activity of NF-κB and ROS production in LPS-activated RAW 264.7 cells. J Ethn Pharmacol 113:149–155Google Scholar
- 38.Ihara H, Yamamoto H, Ida T, Tsutsuki H, Sakamoto T, Fujita T, Okada T, Kozaki S (2012) Inhibition of nitric oxide production and inducible nitric oxide synthase expression by a polymethoxyflavone from young fruits of Citrus unshiu in rat primary astrocytes. Biosci Biotechnol Biochem 76:1843–1848CrossRefGoogle Scholar
- 55.Lee MH, Yoon S, Moon JO (2004) The flavonoid naringenin inhibits dimethylnitrosamine-induced liver damage in rats. Biol Pharm Bull 27:72–76Google Scholar