Silibinin attenuates cardiac hypertrophy and fibrosis through blocking EGFR-dependent signaling

• Published in: Journal of cellular biochemistry Vol. 110; no. 5; pp. 1111 - 1122
• Main Authors: Ai, Wen, Zhang, Yan, Tang, Qi-Zhu, Yan, Ling, Bian, Zhou-Yan, Liu, Chen, Huang, He, Bai, Xue, Yin, Lu, Li, Hongliang
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.08.2010
• Subjects: Angiotensin II - pharmacology; Animals; Animals, Newborn; Blotting, Western; cardiac hypertrophy; Cardiomegaly - metabolism; Cardiomegaly - prevention & control; Cell Shape - drug effects; Cells, Cultured; Dose-Response Relationship, Drug; EGFR; Fibrosis; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Male; Mice; Mice, Inbred C57BL; Myocardium - metabolism; Myocardium - pathology; Myocytes, Cardiac - cytology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation - drug effects; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Sprague-Dawley; Receptor, Epidermal Growth Factor - metabolism; Signal Transduction - drug effects; signaling pathway; silibinin; Silymarin - pharmacology
• ISSN: 0730-2312; 1097-4644
• 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‐κB and TGF‐β1/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. J. Cell. Biochem. 110: 1111–1122, 2010. Published 2010 Wiley‐Liss, Inc.