In this study, we used ICI 182 780 (ICI), an estrogen receptor (ER) antagonist, to investigate the estrogenic activity of Danshen, and to further explored whether Danshen extract can block Leu27IGF‐II‐induced hypertrophy in H9c2 cardiomyoblast cells. We first used an IGF‐II analog Leu27IGF‐II, which specifically activates IGF2R signaling cascades and induces H9c2 cardiomyoblast cell hypertrophy. However, Danshen extract completely inhibited Leu27IGF‐II‐induced cell size increase, ANP and BNP hypertrophic marker expression, and IGF2R induction. We also observed that Danshen extract inhibited calcineurin protein expression and NFAT3 nuclear translocation, leading to suppression of Leu27IGF‐II‐induced cardiac hypertrophy. Moreover, the anti‐Leu27IGF‐II‐IGF2R signaling effect of Danshen was totally reversed by ICI, which suggest the cardio protective effect of Danshen is mediated through estrogen receptors. Our study suggests that, Danshen exerts estrogenic activity, and thus, it could be used as a selective ER modulator in IGFIIR induced hypertrophy model.

中文翻译：

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丹参（丹参）抑制 Leu27 IGF-II 诱导的 H9c2 细胞肥大

在本研究中，我们使用雌激素受体 (ER) 拮抗剂 ICI 182 780 (ICI) 来研究丹参的雌激素活性，并进一步探讨丹参提取物是否可以阻断 Leu27IGF-II 诱导的 H9c2 心肌细胞肥大。我们首先使用 IGF-II 类似物 Leu27IGF-II，它特异性激活 IGF2R 信号级联并诱导 H9c2 心肌细胞肥大。然而，丹参提取物完全抑制了 Leu27IGF-II 诱导的细胞大小增加、ANP 和 BNP 肥大标志物的表达以及 IGF2R 的诱导。我们还观察到丹参提取物抑制钙调神经磷酸酶蛋白表达和 NFAT3 核易位，从而抑制 Leu27IGF-II 诱导的心脏肥大。此外，丹参的抗 Leu27IGF-II-IGF2R 信号效应被 ICI 完全逆转，这表明丹参的心脏保护作用是通过雌激素受体介导的。我们的研究表明，丹参发挥雌激素活性，因此，它可以用作 IGFIIR 诱导的肥大模型中的选择性 ER 调节剂。