Hoshovs'ka Iu V, Korkach Iu P, Shymans'ka T V, Kotsiuruba A V, Sahach V F
Fiziol Zh (1994). 2009;55(6):3-11.
Genipin is aglycone of geniposide, one of the active compounds of Gardenia gasminoides Ellis. The gardenia fruit extract has been used in traditional Chinese medicine to relieve the symptoms of type 2 diabetes that is accompanied with extensive oxidative stress and endothelial dysfunction of NO production. Besides, genipin was shown to inhibit UCP-depended proton leak through the inner mitochondrial membrane that leads to increased membrane potential and ATP production. We studied the effects of genipin at ischemia/reperfusion-induced oxidative stress and activity of NOS isozymes using Langendorfperfused old rat heart model. Ischemia/reperfusion is well-known oxidative agent, and showed significant increasing of superoxide radical, hydrogen peroxide and hydroxyl radical. Genipin application in doze 10-5 mol/L for 15 min before prolonged ischemia exerted powerful antiradical and antilipoperoxidative effects. Heart ischemia/reperfusion was supported with peroxynitrite generation and nitrozative stress. We demonstrated the inhibitory property of genipin on INOS expression that possibly occurs via protein kinase A inhibition and stabilization of I-kappaB-NF-kappaB complex. Genipin stimulated cNOS activity seemingly activating PI3K/Akt signaling pathway. Although, post-ischemic recovery ofcardiodynamic parameters of old rat hearts were depressed due to "switching off" the NO production by inducible NOS which is important in early period of reperfusion. Thus, we conclude that genipin is powerfull antioxidant and posses insulin-like activity due to its property of managing the NO production at intracellular signal transduction cascade level.
京尼平是栀子苷的苷元，栀子苷是栀子的活性成分之一。栀子果实提取物已被用于传统中药中，以缓解伴有广泛氧化应激和一氧化氮生成的内皮功能障碍的2型糖尿病症状。此外，已证明京尼平可抑制通过线粒体内膜的UCP依赖性质子泄漏，从而导致膜电位增加和ATP生成增加。我们使用Langendorf灌注的老龄大鼠心脏模型研究了京尼平对缺血/再灌注诱导的氧化应激和一氧化氮合酶同工酶活性的影响。缺血/再灌注是众所周知的氧化剂，可导致超氧阴离子、过氧化氢和羟自由基显著增加。在长时间缺血前15分钟应用10-5mol/L剂量的京尼平可产生强大的抗自由基和抗脂质过氧化作用。心脏缺血/再灌注伴随着过氧亚硝酸盐的生成和亚硝化应激。我们证明了京尼平对诱导型一氧化氮合酶表达的抑制作用，这可能是通过抑制蛋白激酶A和稳定I-κB-NF-κB复合物实现的。京尼平似乎通过激活PI3K/Akt信号通路刺激组成型一氧化氮合酶活性。尽管如此，老龄大鼠心脏的心脏动力学参数在缺血后的恢复因诱导型一氧化氮合酶在再灌注早期“关闭”一氧化氮生成而受到抑制。因此，我们得出结论，京尼平是一种强大的抗氧化剂，由于其在细胞内信号转导级联水平上调节一氧化氮生成的特性，具有胰岛素样活性。
