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Silibinin attenuates cardiac hypertrophy and fibrosis through blocking EGFR-dependent signaling
Wen Ai1, Yan Zhang, Qi-Zhu Tang
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China.
Insights
Silibinin, a compound that suppresses epidermal growth factor receptor (EGFR), was found to effectively reduce cardiac hypertrophy. This protective effect involves blocking EGFR signaling, inflammation, and fibrosis in heart cells.
Area of Science:
- Cardiovascular Biology
- Molecular Pharmacology
Background:
- Cardiac hypertrophy is a significant risk factor for heart failure.
- Epidermal growth factor receptor (EGFR) signaling is implicated in the development of cardiac hypertrophy.
Purpose of the Study:
- To investigate the potential of silibinin in attenuating cardiac hypertrophy by disrupting EGFR signaling.
- To examine the effects of silibinin on EGFR-dependent signaling pathways, inflammation, and fibrosis in cardiac cells and an animal model.
Main Methods:
- Neonatal cardiac myocytes and fibroblasts were treated with angiotensin II (Ang II) to induce hypertrophy.
- An aortic banding (AB) mouse model was used to simulate pressure overload.
- EGFR generation, downstream signaling cascades (ERK1/2, PI3K/Akt), and inflammatory/fibrotic markers (NF-kappaB, TGF-beta1/Smad) were assessed.
Main Results:
- Silibinin significantly inhibited cardiac hypertrophic responses induced by pressure overload.
- Silibinin reduced EGFR generation and attenuated EGFR-dependent ERK1/2 and PI3K/Akt signaling.
- Silibinin decreased inflammation and fibrosis by inhibiting NF-kappaB and TGF-beta1/Smad pathways.
Conclusions:
- Silibinin demonstrates potential in protecting against cardiac hypertrophy, inflammation, and fibrosis.
- The cardioprotective effects of silibinin are mediated through the blockade of EGFR activity and its downstream signaling pathways.
Abstract:
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.
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