15 research outputs found

    Loureirin B, an essential component of Sanguis Draxonis, inhibits Kv1.3 channel and suppresses cytokine release from Jurkat T cells

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    Sanguis draxonis (SD), also known as “Dragon’s Blood”, is a traditional herb medicine that has been used to treat a variety of complications with unknown mechanisms. Recent studies show that SD displays immunosuppressive activities and improves symptoms of type I diabetes in animal models. However, the mechanisms underlying SD’s immunosuppressive actions are not completely understood. The voltage-gated Kv1.3 channel plays a critical role in the pathogenesis of autoimmune diseases by regulating the functions of both T cells and B cells. Here we investigated the effect of SD and one of its active components loureirin B (LrB) on Kv1.3. Both SD and LrB inhibited Kv1.3-mediated currents, produced a membrane depolarization, and reduced Ca(2+) influx in Jurkat T cells. In addition, application of LrB inhibited phytohemagglutinin (PHA)-induced IL-2 release from activated Jurkat T cells. Furthermore, point mutations in the selective filter region significantly reduced the inhibitory effect of LrB on Kv1.3. The results of these experiments provide evidence that LrB is a channel blocker of Kv1.3 by interacting with amino acid residues in its selective filter region. Direct inhibition of Kv1.3 in T cells by SD and LrB might be the cellular and molecular basis of SD-mediated immunosuppression

    Microwave assisted synthesis and X-ray structure of a novel anthracene-derived aminophosphonate. Enantioseparation of two α-aminophosphonates and genotoxicity in vivo

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    <p>A novel anthracene-derived α-aminophosphonate has been synthesized through a classical addition reaction of dimethyl phosphite to a Schiff base and via a microwave assisted Kabachnik–Fields reaction. The compound has been characterized by elemental analysis, TLC, IR, NMR, and fluorescent spectra. The X-ray analysis showed that the compound crystallizes in the orthorhombic space group <i>Pbca</i> (N° 61) with one molecule per asymmetric unit. The enantioseparation of two racemic aminophosphonates (<b>5</b> and <b>6</b>) into enantiomers (<b>5a, 5b</b> and <b>6a, 6b</b>, respectively) has been performed. Data about genotoxicity and antiproliferative activity in vivo of the racemic compounds and their enantiomeric forms is also presented. The studied racemic α-aminophosphonates <b>5</b> and <b>6</b> and their enantiomers have weak genotoxic effect. Both pairs of enantiomers did not show a significant inhibition of cell dividing processes in the bone marrow cells compared to <b>5</b> and <b>6</b>. The hematopoietic function of the bone marrow will not be discontinued after exposure of the tested compounds.</p
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