Silibinin Attenuates Cardiac Hypertrophy and Fibrosis Through Blocking EGFR-Dependent Signaling

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 an model by aortic banding (AB) mice. Our data revealed that silibinin obviously blocked cardiac hypertrophic responses Induced by pressure overload Meanwhile. slid-rum markedly reduced the increased generation of EGFR Moreover. these beneficial effects were associated with attenuation of the EGFR-dependent ERK 1/2, PI3K/Akt signaling cascade. We further demonstrated silibinin decreased inflammation and fibrosis by blocking the activation of NF-kappa B and TGF-beta 1/Smad signaling pathways in vitro and in viva. 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 J. Cell. Biochem. 110: 1111-1122, 2010 (C) 2010 Wiley-Liss. Inc