Institute of Pharmacy, Nirma University, Sarkhej-Gandhinagar Highway, Ahmedabad, Gujarat, 382 481, India.
Cardiovasc Toxicol. 2019 Feb;19(1):23-35. doi: 10.1007/s12012-018-9470-2.
The present investigation was undertaken to study the effect of silymarin on cardiac hypertrophy induced by partial abdominal aortic constriction (PAAC) in Wistar rats. Silymarin was administered for 9 weeks at the end of which we evaluated hypertrophic, hemodynamic, non-specific cardiac markers, oxidative stress parameters, and determined mitochondrial DNA concentration. Hypertrophic control animals exhibited cardiac hypertrophy, altered hemodynamics, oxidative stress, and decreased mitochondrial DNA (mtDNA) concentration. Treatment with silymarin prevented cardiac hypertrophy, improved hemodynamic functions, prevented oxidative stress and increased mitochondrial DNA concentration. Docking studies revealed that silymarin produces maximum docking score with mitogen-activated protein kinases (MAPK) p38 as compared to other relevant proteins docked. Moreover, PAAC-control rats exhibited significantly increased expression of MAPK p38β mRNA levels which were significantly decreased by the treatment of silymarin. Our data suggest that silymarin produces beneficial effects on cardiac hypertrophy which are likely to be mediated through inhibition of MAPK p38β.
本研究旨在探讨水飞蓟素对部分腹主动脉缩窄(PAAC)诱导的 Wistar 大鼠心肌肥厚的影响。水飞蓟素在 9 周后给药,在此期间我们评估了肥厚、血流动力学、非特异性心脏标志物、氧化应激参数,并测定了线粒体 DNA 浓度。肥厚对照组动物表现出心肌肥厚、血流动力学改变、氧化应激和线粒体 DNA(mtDNA)浓度降低。水飞蓟素治疗可预防心肌肥厚、改善血流动力学功能、预防氧化应激并增加线粒体 DNA 浓度。对接研究表明,与其他相关对接蛋白相比,水飞蓟素与丝裂原活化蛋白激酶(MAPK)p38 产生最大的对接评分。此外,PAAC 对照组大鼠 MAPK p38β mRNA 水平显著升高,而水飞蓟素治疗后显著降低。我们的数据表明,水飞蓟素对心肌肥厚有有益的作用,可能是通过抑制 MAPK p38β 介导的。