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The present study was designed to investigate the anti-inflammatory effects of a new derivative of hydroxytyrosol (HTy), peracetylated hydroxytyrosol (Per-HTy), compared with its parent, HTy, on lipopolysaccharide (LPS)-stimulated murine macrophages as well as potential signaling pathways involved. In particular, we attempted to characterize the role of the inflammasome underlying Per-HTy possible anti-inflammatory effects. Isolated murine peritoneal macrophages were treated with HTy or its derivative in the presence or absence of LPS (5 μg/ml) for 18 h. Cell viability was determined using sulforhodamine B (SRB) assay. Nitric oxide (NO) production was analyzed by Griess method. Production of pro-inflammatory cytokines was evaluated by enzyme-linked immunosorbent assay (ELISA) and inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway (STAT3), haem oxigenase 1 (HO1), nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression and mitogen-activated protein kinases (MAPKs) activation was determined by Western blot. Per-HTy significantly reduced the levels of NO and pro-inflammatory cytokines as well as both COX-2 and iNOS expressions. Furthermore, Per-HTy treatment inhibited STAT3 and increased Nrf2 and HO1 protein levels in murine macrophages exposed to LPS. In addition, Per-HTy anti-inflammatory activity was related with an inhibition of non-canonical nucleotide binding domain (NOD)-like receptor (NLRP3) inflammasome pathways by decreasing pro-inflammatory interleukin (IL)-1β and IL-18 cytokine levels as consequence of regulation of cleaved caspase-11 enzyme. These results support that this new HTy derivative may offer a new promising nutraceutical therapeutic strategy in the management of inflammatory-related pathologies. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a widespread organ involvement. Recent studies have suggested that extra virgin olive oil (EVOO) might possess preventive effects on this immunoinflammation-related disease. However, its role in SLE remained unknown. In this work, we evaluated the effects of EVOO diet in a pristane-induced SLE model in mice. Three-month-old mice received an injection of pristane or saline solution and were fed with different experimental diets: sunflower oil diet or EVOO diet. After 24weeks, mice were sacrificed, spleens were collected and kidneys were removed for immunoinflammatory detections. The kidney expression of microsomal prostaglandin E synthase 1, heme oxygenase 1 (HO-1), nuclear factor E2-related factor 2 (Nrf-2), mitogen-activated protein kinases (MAPKs), Janus kinase/signal transducer and activator of transcription (JAK/STAT) and nuclear transcription factor-kappa B (NF-κB) pathways were studied by western blotting. In addition to macroscopic and histological analyses, serum matrix metalloproteinase 3 (MMP-3) levels and proinflammatory cytokines production in splenocytes were evaluated by enzyme-linked immunoassay. We have demonstrated that EVOO diet significantly reduced renal damage and decreased MMP-3 serum and PGE2 kidney levels as well as the proinflammatory cytokines production in splenocytes. Our data indicate that Nrf-2 and HO-1 protein expressions were up-regulated in those mice fed with EVOO and the activation of JAK/STAT, MAPK and NF-κB pathways were drastically ameliorated. These results support the interest of EVOO as a beneficial functional food exerting a preventive/palliative role in the management of SLE. [ABSTRACT FROM AUTHOR]

Hydroxytyrosol, a polyphenolic compound from extra virgin olive oil (EVOO) has exhibited an improvement in a model of DSS-induced colitis. However, other phenolic compounds present such as hydroxytyrosyl acetate (HTy-Ac) and 3,4-dihydroxyphenylglycol (DHPG) need to be explored to complete the understanding of the overall effects of EVOO on inflammatory colon mucosa. This study was designed to evaluate the effect of both HTy-Ac and DHPG dietary supplementation in the inflammatory response associated to colitis model. Six-week-old mice were randomized in four dietary groups: sham and control groups received standard diet, and other two groups were fed with HTy-Ac and DHPG, respectively, at 0.1%. After 30 days, all groups except sham received 3% DSS in drinking water for 5 days followed by a regime of 5 days of water. Acute inflammation was evaluated by Disease Activity Index (DAI), histology and myeloperoxidase (MPO) activity. Colonic expression of iNOS, COX-2, MAPKs, NF- k B and FOXP3 were determined by western blotting. Only HTy-Ac-supplemented group showed a significant DAI reduction as well as an improvement of histological damage and MPO. COX-2 and iNOS protein expression were also significantly reduced. In addition, this dietary group down-regulated JNK phosphorylation and prevented the DSS-induced nuclear translocation level of p65. However, no significant differences were observed in the FOXP3 expression. These results demonstrated, for the first time, that HTy-Ac exerts an antiinflammatory effect on acute ulcerative colitis. We concluded that HTy-Ac supplement might provide a basis for developing a new dietary strategy for the prevention of ulcerative colitis. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Cistus albidus L. (Cistaceae) has been traditionally used to treat various inflammatory diseases, but no systematic studies on the anti-inflammatory and anti-nociceptive actions of C. albidus and its putative mechanism have been reported. We aimed to explore the anti-inflammatory and anti-nociceptive effects of this plant and to characterize its polyphenolic composition by liquid chromatography coupled to mass spectrometry (MS). Materials and methods A chloroform extract derived from C. albidus leaves was obtained by solid-liquid and liquid-liquid extraction. The tail immersion test and acetic-acid-induced writhing test were used to evaluate the anti-nociceptive action, while the experimental λ-carrageenan-induced paw edema model was used to test the anti-inflammatory action. Changes in cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) expression, as well as the role of mitogen-activated protein kinases (MAPKs) and the nuclear transcription factor kappa B (NF-kB) signaling pathways on lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages were analyzed by western blotting. HPLC with diode array detection coupled to tandem mass spectrometry detection with electrospray ionization (HPLC-DAD-ESI-MS/MS) was performed to determine the phytochemical profile of the extract. Results Significant anti-nociceptive activity was observed both in the tail immersion (59.63% reduction at 120 min) and in the acetic acid (65.94% inhibition) tests at 100 mg/kg. The extract (50 mg/kg) exhibited a substantial reduction in paw edema (51.6%) and significantly inhibited nitrite generation (72.62%) without affecting cell viability of LPS-stimulated murine peritoneal macrophages. These results were concomitant with a down-regulation of the pro-inflammatory enzymes COX-2 and iNOS in extract-treated macrophages and a decrease in p38 MAPK phosphorylation. HPLC-DAD-ESI-MS/MS analysis revealed that flavonols such as kaempferol and quercetin derivatives were potentially responsible for such effects. Conclusion These results support the widespread use of C. albidus in popular medicine and indicate that this plant has therapeutic potential with analgesic and anti-inflammatory properties based on the presence of flavonol derivatives. [ABSTRACT FROM AUTHOR]