Gabrielová Eva, Zholobenko Aleksey Vladimirovich, Bartošíková Lenka, Nečas Jiří, Modriansky Martin
Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic.
Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic.
PLoS One. 2015 Sep 29;10(9):e0139208. doi: 10.1371/journal.pone.0139208. eCollection 2015.
2,3-dehydrosilybin (DHS) is a minor flavonolignan component of Silybum marianum seed extract known for its hepatoprotective activity. Recently we identified DHS as a potentially cardioprotective substance during hypoxia/reoxygenation in isolated neonatal rat cardiomyocytes. This is the first report of positive inotropic effect of DHS on perfused adult rat heart. When applied to perfused adult rat heart, DHS caused a dose-dependent inotropic effect resembling that of catecholamines. The effect was apparent with DHS concentration as low as 10 nM. Suspecting direct interaction with β-adrenergic receptors, we tested whether DHS can trigger β agonist-dependent gene transcription in a model cell line. While DHS alone was unable to trigger β agonist-dependent gene transcription, it enhanced the effect of isoproterenol, a known unspecific β agonist. Further tests confirmed that DHS could not induce cAMP accumulation in isolated neonatal rat cardiomyocytes even though high concentrations (≥ 10 μM) of DHS were capable of decreasing phosphodiesterase activity. Pre-treatment of rats with reserpine, an indole alkaloid which depletes catecholamines from peripheral sympathetic nerve endings, abolished the DHS inotropic effect in perfused hearts. Our data suggest that DHS causes the inotropic effect without acting as a β agonist. Hence we identify DHS as a novel inotropic agent.
2,3-脱氢水飞蓟宾（DHS）是水飞蓟种子提取物中的一种次要黄酮木脂素成分，以其肝脏保护活性而闻名。最近，我们在分离的新生大鼠心肌细胞缺氧/复氧过程中，将DHS鉴定为一种潜在的心脏保护物质。这是关于DHS对灌注成年大鼠心脏具有正性肌力作用的首次报道。当应用于灌注成年大鼠心脏时，DHS引起了类似于儿茶酚胺的剂量依赖性正性肌力作用。在低至10 nM的DHS浓度下，这种作用就很明显。由于怀疑其与β-肾上腺素能受体直接相互作用，我们在一个模型细胞系中测试了DHS是否能触发β激动剂依赖性基因转录。虽然单独的DHS无法触发β激动剂依赖性基因转录，但它增强了异丙肾上腺素（一种已知的非特异性β激动剂）的作用。进一步的测试证实，即使高浓度（≥10 μM）的DHS能够降低磷酸二酯酶活性，它也不能在分离的新生大鼠心肌细胞中诱导cAMP积累。用利血平（一种从外周交感神经末梢消耗儿茶酚胺的吲哚生物碱）预处理大鼠，消除了DHS在灌注心脏中的正性肌力作用。我们的数据表明，DHS引起正性肌力作用，但不作为β激动剂。因此，我们将DHS鉴定为一种新型的正性肌力药物。
