Naringenin inhibits transforming growth factor-β1-induced cardiac fibroblast proliferation and collagen synthesis via G0/G1 arrest.

The Traditional Chinese Medicine naringenin (NRG) has a number of biological effects, including anti-inflammatory, anti-oxidative, anti-tumor and anti-atherosclerotic effects. However, the mechanism underlying its effects remains unclear. The aim of the present study is to investigate the role and mechanism of NRG on proliferation and collagen synthesis of cardiac fibroblasts (CFs) induced by transforming growth factor β1 (TGF-β1). Firstly, proliferation and collagen synthesis in CFs subjected to TGF-β1 was assessed subsequent to the consumption of NRG or control treatment. Additionally, the cell cycle of different groups and the roles of cyclins and cyclin-dependent kinases (CDKs) in NRG treatment of CFs were detected. In the present study, it was revealed that treatment of CFs with NRG resulted in attenuated fibroblast α-smooth muscle actin expression, deceased proliferation and collagen synthesis when compared with a TGF-β1 stimulus. Additionally, it was demonstrated that cell population of CFs treated with NRG in the S-phase became smaller whereas that of CFs in the G0/G1-phase increased when compared with the TGF-β1 group. Mechanistically, the expression of cyclin D1-CDK4/6 and cyclin E2-CDK2 were inhibited in the NRG treatment group. These results illustrated that the protective effects of NRG on proliferation and collagen synthesis of CFs were at least in part due to G0/G1 arrest. Therefore, NRG may become a novel strategy for treating cardiac fibrosis in the future.