Peracetylated hydroxytyrosol,a new hydroxytyrosol derivate,attenuates LPS-induced inflammatory response in murine peritoneal macrophages via regulation of non-canonical inflammasome,Nrf2/HO1 and JAK/STAT signaling pathways |
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| Affiliation: | 1. Department of Pharmacology, Faculty of Pharmacy, University of Seville, Spain;2. Department of Organic Chemistry, Faculty of Chemistry, University of Seville, Spain;1. Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada, R3T 2N2;2. Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, MB, Canada, R2H 2A6;3. Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, Winnipeg, MB, Canada, R2H 2A6.;1. Food Technology Department, UTPV-XaRTA, Agrotecnio Research Center, University of Lleida, Alcalde Rovira Roure 191, 25198 Lleida, Spain;2. School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551, Singapore;3. Animal Facilities, Campus Ciències de la Salut, Facultat de Medicina, University of Lleida, C/Montserrat Roig 2, 25008 Lleida, Spain;1. Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College St., Toronto, Ontario, Canada, M5S 3E2;2. Department of Kinesiology, Faculty of Applied Health Sciences, University of Waterloo, 200 University Ave. W., Waterloo, Ontario, Canada, N2L 3G1;3. Lipid Biology, Nestlé Institute of Health Sciences, EPFL Innovation Park, Bâtiments G & H, 1015 Lausanne, Switzerland |
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| Abstract: | 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. |
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