Browsing by Subject "Anti-inflammatory"

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    Inactivation of lipoxygenase and cyclooxygenase by natural betalains and semi-synthetic analogues
    (Elsevier, 2014-01-13) Vidal, Pedro J.; Gandía Herrero, Fernando; López Nicolás, José Manuel; García Carmona, Francisco; Bioquímica y Biología Molecular "A"
    Betalains are natural pigments characteristic of plants of the order Caryophyllales. In this work, the role of betalains in the anti-inflammatory activity described for plant extracts is analysed in terms of the inactivation of the enzymes involved in the biochemical response (lipoxygenase and cyclooxygenase). Pure natural betalains and semi-synthetic analogues are demonstrated to promote a significant reduction of the enzymes activity. Reactions were followed spectrophotometrically and by HPLC-DAD. Phenethylamine-betaxanthin was the most potent in the inactivation of cyclooxygenase, with a reduction of 32% of the control activity at 125 lM, while the natural pigment betanidin and a betalain analogue derived from indoline resulted as the most potent inactivators of lipoxygenase, with IC50 values of 41.4 and 40.1 lM, respectively. Molecular docking studies revealed that betalains interact with the lipoxygenase amino acids involved in substrate binding and with Tyr-385 and Ser-530 close to the yclooxygenase active site, interfering in enzyme catalysis.
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    Robust In vitro and in vivo immunosuppressive and anti-inflammatory properties of Inducible caspase-9-mediated apoptotic mesenchymal stromal/stem cell
    (Oxford University Press , 2022-03-03) Romecín, Paola Alejandra; Vinyoles, Meritxell; López-Millán, Belén; Diaz de la Guardia, Rafael; Marín Atucha, Noemí; Querol, Sergi; Bueno, Clara; Benitez, Raquel; González-Rey, Elena; Delgado, Mario; Menéndez, Pablo; Fisiología; Facultad de Medicina
    Mesenchymal stromal stem/cells (MSC) therapies are clinically used in a wide range of disorders based on their robust HLA-independent immunosuppressive and anti-inflammatory properties. However, the mechanisms underlying MSC therapeutic activity remain elusive as demonstrated by the unpredictable therapeutic efficacy of MSC infusions reported in multiple clinical trials. A seminal recent study showed that infused MSCs are actively induced to undergo apoptosis by recipient cytotoxic T cells, a mechanism that triggers in vivo recipient-induced immunomodulation by such apoptotic MSCs, and the need for such recipient cytotoxic cell activity could be replaced by the administration of ex vivo-generated apoptotic MSCs. Moreover, the use of MSC-derived extracellular vesicles (MSC-EVs) is being actively explored as a cell-free therapeutic alternative over the parental MSCs. We hypothesized that the introduction of a "suicide gene" switch into MSCs may offer on-demand in vivo apoptosis of transplanted MSCs. Here, we prompted to investigate the utility of the iCasp9/AP1903 suicide gene system in inducing apoptosis of MSCs. iCasp9/AP1903-induced apoptotic MSCs (MSCiCasp9+) were tested in vitro and in in vivo models of acute colitis. Our data show a very similar and robust immunosuppressive and anti-inflammatory properties of both "parental" alive MSCGFP+ cells and apoptotic MSCiCasp9+ cells in vitro and in vivo regardless of whether apoptosis was induced in vivo or in vitro before administering MSCiCasp9+ lysates. This development of an efficient iCasp9 switch may potentiate the safety of MSC-based therapies in the case of an adverse event and, will also circumvent current logistic technical limitations and biological uncertainties associated to MSC-EVs.