Apigenin supplementation protects the development of dextran sulfate sodium-induced murine experimental colitis by inhibiting canonical and non-canonical inflammasome signaling pathways.

The present study was designed to elucidate the protective effects of dietary apigenin (API) enrichment in a chronic colitis model induced by DSS in mice. Inflammatory mediators and the possible role of canonical and non-canonical NLRP3 inflammasome signaling pathways in the beneficial effects of API under chronic inflammatory conditions were also explored. Six-week-old mice were randomized in four dietary groups: sham and control groups received standard diet (SD), and other two groups were fed with API at 0.1%. After 30days, all groups except sham received 3% DSS in drinking water for 5days followed by a regime of 21days of water. Our results revealed that dietary API supplementation decreased the macroscopic and microscopic damage signs of colitis; also, it was capable to down-regulate mPGES, COX-2 and iNOS enzyme colonic expressions and to decrease serum matrix metalloproteinase (MMP-3) levels. Similarly, API diet reduced IL-1ß and TNF-α proinflammatory cytokine secretions in primary LPS-stimulated splenocytes. Furthermore, we demonstrated that API anti-inflammatory activity was related with an inhibition of both canonical and non-canonical NLRP3 inflammasome pathways by decreasing proinflammatory IL-1ß and IL-18 cytokine levels as a consequence of regulation of cleaved caspase-1 and caspase-11 enzymes. We conclude that API supplement might provide a basis for developing a new dietary strategy for the prevention of chronic ulcerative colitis.

Anti-inflammatory effects of Retama monosperma in acute ulcerative colitis in rats

Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn’s disease, is a chronic intestinal disorder resultant from a dysfunctional epithelial, innate and adaptive immune response to intestinal microorganisms. Current IBD treatment presents limitations in both efficacy and safety that stimulated for new active drugs. Retama spp. have been traditionally used in the Mediterranean region in treatment of pain and inflammation. In this study, the anti-inflammatory and protective properties of a standardised aqueous extract from Retama monosperma (RmE) was evaluated in vivo, by intra-colonic administration of trinitrobenzene sulfonic acid (TNBS) in rats as a Crohn’s disease model. The qualitative and quantitative analysis of flavonoids from RmE was performed by high-performance liquid chromatography-tandem mass spectrometry. Oral administration of RmE diminished the severity and extension of the intestinal injuries induced by TNBS. In addition, RmE increased mucus production in goblet cells in colon mucosa, decreased neutrophil infiltration and cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) overexpression. Similarly, RmE significantly reduced p38 mitogen-activated protein kinase activation, preventing the inhibitory protein IêB degradation in colonic mucosa. RmE anti-inflammatory effects seem to be related to impairment of neutrophil function and COX-2 and iNOS down-regulation possibly through p38 MAPK and nuclear transcription factor kappa B signalling pathways. These results suggest that RmE might contribute to the development of new pharmaceutical products for inflammatory bowel disease

Anti-inflammatory effects of Retama monosperma in acute ulcerative colitis in rats.

Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, is a chronic intestinal disorder resultant from a dysfunctional epithelial, innate and adaptive immune response to intestinal microorganisms. Current IBD treatment presents limitations in both efficacy and safety that stimulated for new active drugs. Retama spp. have been traditionally used in the Mediterranean region in treatment of pain and inflammation. In this study, the anti-inflammatory and protective properties of a standardised aqueous extract from Retama monosperma (RmE) was evaluated in vivo, by intra-colonic administration of trinitrobenzene sulfonic acid (TNBS) in rats as a Crohn's disease model. The qualitative and quantitative analysis of flavonoids from RmE was performed by high-performance liquid chromatography-tandem mass spectrometry. Oral administration of RmE diminished the severity and extension of the intestinal injuries induced by TNBS. In addition, RmE increased mucus production in goblet cells in colon mucosa, decreased neutrophil infiltration and cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) overexpression. Similarly, RmE significantly reduced p38 mitogen-activated protein kinase activation, preventing the inhibitory protein IκB degradation in colonic mucosa. RmE anti-inflammatory effects seem to be related to impairment of neutrophil function and COX-2 and iNOS down-regulation possibly through p38 MAPK and nuclear transcription factor kappa B signalling pathways. These results suggest that RmE might contribute to the development of new pharmaceutical products for inflammatory bowel disease.

Oleuropein, a secoiridoid derived from olive tree, inhibits the proliferation of human colorectal cancer cell through downregulation of HIF-1α.

Oleuropein (OL) is the most prominent phenolic compound in the fruit of olive tree. Although OL has shown powerful anticancer activity the underlying action mechanism remains largely unknown. The present study evaluated the effects of OL on hydroxityrosol (HT)-29 human colon adenocarcinoma cells in comparison to hydroxytyrosol, its hydrolysis product, and to elucidate the underlying anticancer molecular mechanisms involved. Cell proliferation was determined using SRB assay. Cell cycle and apoptosis were assessed by flow cytometry and changes in MAPK cascade protein expression, HIF-1α, p53, PPARγ, and NFKß signaling pathways by Western blot. Although OL showed less potency than HT, in terms of cell growth inhibition, induced significant changes in cell cycle analysis and caused a significant increase in the apoptotic population. Both compounds produced a remarkable decrease in HIF-1α protein and an upregulation of p53 protein expression. However, no significant changes in IkB-α and MAPK cascade protein expressions were observed. HT produced a significant upregulation in peroxisome proliferator-activated receptor gamma (PPARγ) expression whereas OL failed. PPARγ upregulation may be one of the principal mechanisms of the tumor shrinkage by HT. Our novel findings demonstrate that OL limits the growth and induces apoptosis in HT-29 cells via p53 pathway activation adapting the HIF-1α response to hypoxia.