Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China.
J Cell Biochem. 2010 Aug 1;110(5):1111-22. doi: 10.1002/jcb.22623.
Cardiac hypertrophy is a major determinant of heart failure. The epidermal growth factor receptor (EGFR) plays an important role in cardiac hypertrophy. Since silibinin suppresses EGFR in vitro and in vivo, we hypothesized that silibinin would attenuate cardiac hypertrophy through disrupting EGFR signaling. In this study, we examined this hypothesis using neonatal cardiac myocytes and fibroblasts induced by angiotensin II (Ang II) and animal model by aortic banding (AB) mice. Our data revealed that silibinin obviously blocked cardiac hypertrophic responses induced by pressure overload. Meanwhile, silibinin markedly reduced the increased generation of EGFR. Moreover, these beneficial effects were associated with attenuation of the EGFR-dependent ERK1/2, PI3K/Akt signaling cascade. We further demonstrated silibinin decreased inflammation and fibrosis by blocking the activation of NF-kappaB and TGF-beta1/Smad signaling pathways in vitro and in vivo. Our results indicate that silibinin has the potential to protect against cardiac hypertrophy, inflammation, and fibrosis through blocking EGFR activity and EGFR-dependent different intracellular signaling pathways.
心肌肥厚是心力衰竭的主要决定因素。表皮生长因子受体（EGFR）在心肌肥厚中发挥重要作用。由于水飞蓟素在体外和体内均能抑制 EGFR，我们假设水飞蓟素通过破坏 EGFR 信号通路来减轻心肌肥厚。在这项研究中，我们使用血管紧张素 II（Ang II）诱导的乳鼠心肌细胞和成纤维细胞以及主动脉缩窄（AB）小鼠动物模型来检验这一假说。我们的数据表明，水飞蓟素明显阻断了由压力超负荷引起的心肌肥厚反应。同时，水飞蓟素显著降低了 EGFR 的增加生成。此外，这些有益的作用与 EGFR 依赖性 ERK1/2、PI3K/Akt 信号级联的衰减有关。我们还进一步证明，水飞蓟素通过阻断 NF-kappaB 和 TGF-beta1/Smad 信号通路的激活，在体外和体内减轻了炎症和纤维化。我们的结果表明，水飞蓟素通过阻断 EGFR 活性和 EGFR 依赖性不同的细胞内信号通路，具有预防心肌肥厚、炎症和纤维化的潜力。
