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 Physiology, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic.
Fitoterapia. 2019 Jan;132:12-21. doi: 10.1016/j.fitote.2018.10.028. Epub 2018 Oct 30.
2,3-dehydrosilybin (DHS) is a minor component of silymarin, Silybum marianum seed extract, used in some dietary supplements. One of the most promising activities of this compound is its anticancer and cardioprotective activity that results, at least partially, from its cytoprotective, antioxidant, and chemopreventive properties. The present study investigated the cardioprotective effects of DHS in myocardial ischemia and reperfusion injury in rats. Isolated hearts were perfused by the Langendorff technique with low dose DHS (100 nM) prior to 30 min of ischemia induced by coronary artery occlusion. After 60 min of coronary reperfusion infarct size was determined by triphenyltetrazolium staining, while lactatedehydrogenase activity was evaluated in perfusate samples collected at several timepoints during the entire perfusion procedure. Signalosomes were isolated from a heart tissue after reperfusion and involved signalling proteins were detected. DHS reduced the extent of infarction compared with untreated control hearts at low concentration; infarct size as proportion of ischemic risk zone was 7.47 ± 3.1% for DHS versus 75.3 ± 4.8% for ischemia. This protective effect was comparable to infarct limitation induced by ischemic preconditioning (22.3 ± 4.5%). Selective inhibition of Src-family kinases with PP2 (4-Amino-3-(4-chlorophenyl)-1-(t-butyl)-1H-pyrazolo[3,4-d]pyrimidine) abrogated the protection afforded by DHS. This study provides experimental evidence that DHS can mediate Src-kinase-dependent cardioprotection against myocardial damage produced by ischemia/reperfusion injury.
2,3-脱水硅蓟素 (DHS) 是水飞蓟宾的次要成分，水飞蓟宾是水飞蓟种子提取物的一种成分，用于一些膳食补充剂中。这种化合物最有前途的活性之一是其抗癌和心脏保护活性，这至少部分归因于其细胞保护、抗氧化和化学预防特性。本研究调查了 DHS 在大鼠心肌缺血再灌注损伤中的心脏保护作用。用 Langendorff 技术对离体心脏进行灌注，在冠状动脉闭塞引起 30 分钟缺血之前用低剂量 DHS（100nM）进行预处理。在冠状动脉再灌注 60 分钟后，通过三苯基四氮唑染色确定梗塞面积，同时在整个灌注过程中收集灌注样品的多个时间点评估乳酸脱氢酶活性。在再灌注后从心脏组织中分离信号体，并检测涉及的信号蛋白。与未处理的对照心脏相比，DHS 在低浓度下减少了梗塞的程度；梗塞面积与缺血危险区的比例为 DHS 组为 7.47±3.1%，缺血组为 75.3±4.8%。这种保护作用与缺血预处理诱导的梗塞限制（22.3±4.5%）相当。用 PP2（4-氨基-3-(4-氯苯基)-1-(叔丁基)-1H-吡唑并[3,4-d]嘧啶）选择性抑制Src 家族激酶，可消除 DHS 提供的保护作用。本研究提供了实验证据，表明 DHS 可以介导 Src 激酶依赖性心脏保护作用，对抗缺血再灌注损伤引起的心肌损伤。
