hypoxoside and Inflammatory-Bowel-Diseases

Brachyspira hyodysenteriae is the causative agent of swine dysentery and induces a characteristic mucosal inflammation resulting in pronounced typhlocolitis in swine and mice. Hypoxis hemerocallidea corm (African potato) is a traditional medicine in southern Africa. An African potato methanolic extract (APME) and one of its major constituents, hypoxoside, have been shown in vitro to possess an anti-inflammatory property. The aim of this study is to evaluate the ability of APME to prevent or ameliorate B. hyodysenteriae-induced typhlocolitis. Mice were orally treated with APME for seven days prior to B. hyodysenteriae infection and the treatments continued daily for seven days postinfection (DPI). At the termination of the experiment, weight loss, gross and histological lesions, myeloperoxidase (MPO) activity, and intestinal epithelial proliferation were evaluated. In addition, the protein level of activated p65 subunit of nuclear factor-kappaB (NF-kappaB) and mRNA expression of NF-kappaB-associated genes were also measured. APME treatment significantly (P < 0.05) reduced weight loss, the severity of typhlocolitis, mucosal MPO activity and intestinal epithelial proliferation subsequent to B. hyodysenteriae infection. Mucosal protein levels of active p65 and expression levels of NF-kappaB-associated genes following B. hyodysenteriae infection were also decreased by the oral treatment with APME. In conclusion, prophylactic treatment with APME ameliorated B. hyodysenteriae-induced typhlocolitis, suggesting H. hemerocallidea corm methanolic extract may have potential for ameliorating enteropathies that are mediated by overactive host inflammatory processes.

Topics: Africa, Southern; Alkynes; Animals; Anti-Inflammatory Agents; Brachyspira hyodysenteriae; Cell Proliferation; Disease Models, Animal; Down-Regulation; Glucosides; Gram-Negative Bacterial Infections; Hypoxis; Inflammatory Bowel Diseases; Intestinal Mucosa; Mice; Mice, Inbred C3H; Neutrophils; NF-kappa B; Peroxidase; Phytotherapy; Plant Extracts; Plants, Medicinal; RNA, Messenger; Signal Transduction; Transcription Factor RelA

Susceptibility to inflammatory bowel diseases depends upon interactions between the genetics of the individual and induction of chronic mucosal inflammation. We hypothesized that administration of dietary phenolics, caffeic acid and rutin, would suppress upregulation of inflammatory markers and intestinal damage in a mouse model of colitis. Colitis was induced in C3H/ HeOuJ mice (8 weeks old, 6 male/6 female per treatment) with 1.25% dextran sulfate sodium (DSS) for 6 d in their drinking water. Rutin (1.0 mmol (524 mg)/kg in diet), caffeic acid (1.0 mmol (179 mg)/kg in diet), and hypoxoside extract (15 mg/d, an anticolitic phenolic control) were fed to the mice for 7 d before and during DSS treatment, as well as without DSS treatment. Body weight loss was prevented by rutin and caffeic acid during DSS treatment. Colon lengths in mice fed caffeic acid and hypoxoside during DSS treatment were similar to DSS-negative control. Food intake was improved and myeloperoxidase (MPO) was decreased with each phenolic treatment in DSS-treated mice compared with DSS treatment alone. Colonic mRNA expression of IL-17 and iNOS were inhibited when IL-4 was increased by each phenolic treatment combined with DSS, whereas CYP4B1 mRNA was increased only by caffeic acid in DSS-treated mice, compared with DSS treatment alone. Colonic and cecal histopathology scores of DSS-treated mice were significantly more severe (P < 0.01) than in mice fed caffeic acid before and during DSS treatment, based on mucosal height, necrosis, edema, erosion, and inflammatory cell infiltration. Although both rutin and caffeic acid suppressed the expression of selected inflammatory markers, only caffeic acid protected against DSS-induced colitis, in association with normalization of CYP4B1 expression. The inhibition of DSS-induced colitic pathology by caffeic acid was mediated by mechanisms in addition to anti-inflammatory effects that deserve further study.

Topics: Alkynes; Animals; Antioxidants; Aryl Hydrocarbon Hydroxylases; Body Weight; Caffeic Acids; Colitis; Colon; Dextran Sulfate; Eating; Female; Gene Expression Regulation, Enzymologic; Glucosides; Humans; Inflammatory Bowel Diseases; Interleukin-17; Interleukin-4; Male; Mice; Nitric Oxide Synthase Type II; Organ Size; Peroxidase; RNA, Messenger; Rutin; Time Factors