Intestinal anti-inflammatory effects of goat whey on DNBS-induced colitis in mice

This study evaluated the intestinal anti-inflammatory effects of goat whey in a mouse model of colitis induced by 2,4-dinitrobenzenesulfonic acid that resembles human IBD. At a concentration of 4 g/kg/day, the goat whey improved the symptoms of intestinal inflammation, namely by decreasing the disease activity index, colonic weight/length, and leukocyte infiltration. Moreover, goat whey inhibited NF-kappa B p65 and p38 MAPK signaling pathways and consequently down-regulated the gene expression of various proinflammatory markers such as IL-1 beta, IL-6, IL-17, TNF-alpha, iNOS, MMP-9, ICAM-1. Also, goat whey increased the expression of proteins such as mucins, occludin proteins and cytokine signalling suppressors. The immunomodulatory properties of goat whey were also evaluated in vitro using the murine macrophage cell line Raw 264 and CMT-93 cells derived from mouse rectum carcinomas. The results revealed the ability of goat whey to inhibit the production of NO and reduce IL-6 production in LPS-stimulated cells. In conclusion, goat whey exhibited antiinflammatory effects in the DNBS model of intestinal inflammation, and these observations were confirmed by its immunomodulatory properties in vitro. Together, our results indicate that goat whey could have applications for the treatment of IBD.info:eu-repo/semantics/publishedVersio

Telmisartan Modulates the Oral Mucositis Induced by 5-Fluorouracil in Hamsters

Oral mucositis (OM) is a common adverse effect resulting from cancer therapy. The OM it has implications that may compromise oncologic treatment and decrease the patient’s quality of life. The therapeutic options to prevent or treat the symptoms of OM are scarce; there is no effective therapy that improves the symptoms. Based on the need for further research for the treatment of OM, the present study objective was to evaluate the effect of telmisartan (TELM) on the OM induced by 5-fluorouracil (5-FU), using as animal model Golden Syrian hamsters. 5-FU followed by mechanical trauma on day 4 was used to induce OM in hamsters. Euthanasia occurred on the day 10. The experiments were constituted by the groups saline, mechanical trauma, 5-FU, and TELM in three doses (1, 5, or 10 mg/kg). Macroscopic, histopathological, and immunohistochemical analyses as well as immunofluorescence experiments were performed on the oral mucosa of the animals. The samples also were used for analysis enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reactions (qPCR). TELM (5 or 10 mg/kg) was able to reduce the inflammatory ulceration and infiltration in the oral mucosa of the animals, decreasing the levels of the cytokines TNF-α and IL-1β. These treatments was minimize the immunostaining for cyclooxygenase-2, matrix metalloproteinase-9, transforming growth factor-β, and smad 2/3. The nuclear transcription factor kappa B (NFκB) p65 and inducible nitric oxide synthase were reduced in the oral mucosa. Finally, TELM (10 mg/kg) increased the PPARγ gene expression and reduced STAT1 and NFκB p65 gene expression relative to the 5-FU group. Therefore, TELM prevents the OM produced by 5-FU on animal model

Anti-inflammatory and antinociceptive activities of Phyllanthus niruri spray-dried standardized extract

Phyllanthus niruri L., Euphorbiaceae, spray-dried standardized extract was studied for its anti-inflammatory and antinociceptive activities in adult albino rats and mice. The anti-inflammatory effect of spray-dried standardized extract was observed in carrageenan-induced paw edema and thioglycolate-induced leukocyte migration, while antinociceptive effects were observed using Randall & Selitto, tail flick, and hot plate tests. This study showed that intraperitoneal spray-dried standardized extract at 100, 200, 800, or 1600 mg/kg reduced the vascular response in the inflammatory process of paw edema induced by 1% carrageenan. Oral spray-dried standardized extract at 100 or 200 mg/kg inhibited leukocyte migration to the site of inflammation induced by 3% thioglycolate. In rats, at 100 and 200 mg/kg intraperitoneally, the extract exhibited a marked peripheral analgesic effect in a Randall & Selitto assay and showed significant central analgesic activity in a hot plate and tail flick assay. In conclusion, this study suggested that Phyllanthus niruri spray-dried standardized extract has potent inflammatory and antinociceptive activities and that these activities are not modified by standard drying process, making it feasible to use the dry extract standardized to obtain a phytotherapic preparation and thus validating its use for the treatment of pain and inflammation disorders

Effects of goat whey on gene expression by RT-qPCR and immunofluorescence of the intestinal mucosal barrier proteins as measured.

<p>Colonic gene expression of the barrier function mediators gene expression (A) Mucin (MUC)-2, (B) MUC-3, (C) occludin, (D) zonula occludens (ZO)-1 analyzed by real-time qPCR and normalized with the housekeeping gene, Glyceraldehyde-3-phosphate dehydrohenase (GAPDH) in dinitrobenzene-sulphonic acid (DNBS) mice colitis 4 days after damage induction. Representative confocal photomicrographs of ZO-1 (E) immunoreactivity (green) in colons of the animals from each group; the sections are nuclear counterstained with DAPI (blue): (E.1) Healthy group had moderated ZO-1 labelling; (E.2) ZO-1 labelling was almost absence in DNBS control group; (E.3) ZO-1 labelling (red arrow) was strong in the treated group with goat whey; (E.4) Densitometric analysis confirmed a significant increases in ZO-1 in goat whey. Data are expressed as the means ± SEM. the groups with different letters differ significantly (one-way ANOVA post hoc Tukey’s test, P < 0.05).</p

Effects of goat whey on pro-inflammatory cytokines as measured by ELISA.

<p>Distal colon tissue samples were cultured overnight. The supernatants were assessed for cytokine levels using kits from R&D Systems (Minneapolis, MN, USA) following the manufacturer’s protocols. The cytokine levels in the supernatant were expressed as the concentration in pg/mL. (A) Interleukin (IL)-6 and (B) tumour necrosis factor (TNF)-α production in colonic tissues from mice with 2,4-dinitrobenzenesulfonic acid (DNBS)-induced colitis. Data are expressed as the mean ± SEM (n = 12). The groups with different letters are significantly different (one-way ANOVA post hoc Tukey’s test, P < 0.05).</p

Effect of goat whey on IL-17 expression in colitic mice.

<p>Representative confocal photomicrographs of IL-17 (Panel A) immunoreactivity (green) in colons of the animals from each group; the sections are nuclear counterstained with DAPI (blue): (A.1) Healthy group had absent or weak IL-17 labelling in all mucosa layers; (A.2) IL-17 labelling was strong in the DNBS control group; (A.3) weak to moderate IL-17 labelling (red arrow) was seen in the group treated with goat whey; (A.4) Densitometric analysis confirmed a significant reduction in IL-17 immunoreactivity in goat whey. Data are expressed as the means ± SEM; the groups with different letters differ significantly (one-way ANOVA post hoc Tukey’s test, P < 0.05).</p

Effects of goat whey on the gene expression of pro-inflammatory cytokines as measured by RT-qPCR.

<p>Colonic gene expression of the pro-inflammatory cytokines (A) Interleukin (IL)-1β, (B) IL-6, (C) tumour necrosis factor (TNF)-α, (D) inducible nitric oxide synthase (iNOS), (E) matrix metalloproteinase (MMP)-9, and (F) intercellular adhesion molecule (ICAM)-1 analyzed by real-time qPCR and normalized with the housekeeping gene, Glyceraldehyde-3-phosphate dehydrohenase (GAPDH) in dinitrobenzene-sulphonic acid (DNBS) mice colitis 4 days after damage induction. Data are expressed as the mean ± SEM (n = 12/group). The groups with different letters are significantly different (one-way ANOVA post hoc Tukey’s test, P < 0.05).</p

Effects of goat whey on cell lines.

<p>(A) Nitrite (NO) production and (B) interleukin (IL)-6 levels in Raw 264 and CMT-93 cells, respectively, in basal or LPS-stimulated conditions (100 ng/mL and 1 μg/mL, respectively). Data are expressed as the mean ± SEM. The bars with different letters are significantly different (one-way ANOVA post hoc Tukey’s test, P < 0.05).</p

Composition of goat whey (GW).

<p>Composition of goat whey (GW).</p