Zhejiang Chinese Medical University, Hangzhou 310053, China.
Zhejiang Academy of Medical Sciences, Hangzhou 310007, China.
J Ethnopharmacol. 2015 Jul 1;169:435-40. doi: 10.1016/j.jep.2015.04.026. Epub 2015 Apr 27.
Rhizome and root of Smilax glabra Roxb (Liliaceae family) is a widely used traditional Chinese medicine (TCM) named Tu-fu-ling (TFL) for cardiac disease therapy. The TFL flavonoids (TFLF) has been extracted and proven to possess the anti-cardiac hypertrophy effect in our previous reports. Such effect could be mediated by the modulation of intracellular Ca(2+) flux in myocardial cells, in which junctophilin-2 (JP2) and ryanodine receptor 2 (RyR2) play an important role. However, its mechanism of the anti-cardiac hypertrophy effect remains unclarified.
2μmol/L Ang II was applied to induce hypertrophy model of rat primary cardiomyocytes. After treatment of TFLF at 0.25, 0.5 and 1.0mg/ml, the cell size was microscopic measured, and the protein and mRNA expressions of JP2 and RyR2 in cardiomyocytes were estimated by immunofluorescence imaging, ELISA and real-time PCR assay.
Obvious hypertrophy of cardiomyocytes was induced by Ang II but reversed by TFLF from 0.5 to 1.0mg/ml. The protein and mRNA expressions of JP2 and RyR2 in cardiomyocytes were also inhibited by Ang II but restored by TFLF at its dose range. Such effect of TFLF was exerted at a dose dependent manner, which was even better than that of verapamil.
Our findings may evidence the correlation between JP2/RyR2 and myocardiac hypertrophy, and indicate the JP2/RyR2-mediated anti-hypertrophy mechanism of TFLF for the first time. It deserves to be developed as a promising TCM candidate of new drug for myocardial hypertrophy treatment.
菝葜（百合科菝葜属）的根茎和根是一种广泛使用的传统中药（TCM），名为土茯苓（TFL），用于心脏病治疗。我们之前的研究已经提取并证明 TFL 黄酮（TFLF）具有抗心肌肥大作用。这种作用可能是通过调节心肌细胞内的 Ca(2+) 流来介导的，其中 junctophilin-2 (JP2) 和 Ryanodine 受体 2 (RyR2) 发挥着重要作用。然而，其抗心肌肥大作用的机制尚不清楚。
将 2μmol/L Ang II 应用于诱导大鼠原代心肌细胞肥大模型。在 0.25、0.5 和 1.0mg/ml 的 TFLF 处理后，通过显微镜测量细胞大小，并通过免疫荧光成像、ELISA 和实时 PCR 测定法评估心肌细胞中 JP2 和 RyR2 的蛋白和 mRNA 表达。
Ang II 明显诱导心肌细胞肥大，但 TFLF 从 0.5 到 1.0mg/ml 逆转了这种作用。Ang II 还抑制了心肌细胞中 JP2 和 RyR2 的蛋白和 mRNA 表达，但 TFLF 在其剂量范围内恢复了它们的表达。TFLF 的这种作用呈剂量依赖性，甚至优于维拉帕米。
我们的发现可能证明了 JP2/RyR2 与心肌肥大之间的相关性，并首次表明 TFLF 通过 JP2/RyR2 介导的抗肥大机制。它值得作为一种有前途的心肌肥大治疗中药候选新药进行开发。
