ABSTRACT
Objective It is rarely reported whether myricetin inhibits the activation and function of cardiac fibroblasts and thereby prevents myocardial fibrosis. This study was to investigate the effects of myricetin on the activation,proliferation and secretion of cardiac fibroblasts and its possible molecular mechanisms. Methods Fibroblasts isolated from 1-3 days old rats were cultured and their activation,proliferation and secretion were induced with the transforming growth factor (TGF). The fibroblasts were incubated with myricetin at different concentrations of 1,3,10,30 and 100 μmol/L for 24 hours followed by detection of their proliferation with the CKK8 kit,the transcription levels of fibrotic factors by RT-PCR and the expression levels of α-SMA and signal proteins by immunoflu-orescence staining and Western blot,respectively. Results The expression of α-SMA was significantly up-regulated in the cardiac fi- broblasts of the rats in the TGF-β,30 μmol/L myricetin+TGF-β and 100 μmol/L myricetin+TGF-β groups as compared with that in the control group (P<0.05) but down-regulated in the 30 μmol/L myricetin+TGF-β and 100 μmol/L myricetin+TGF-β groups in com-parison with that in the TGF-β group (P<0.05). At 48 hours,the transcription levels of collagenⅠ,collagenⅢ,fibronectin and con-nective tissue growth factor were markedly higher in the TGF-β,30 μmol/L myricetin+TGF-β and 100 μmol/L myricetin+TGF-β groups than in the control group (P<0.05) but lower in the 30 μmol/L myricetin+TGF-β and 100 μmol/L myricetin+TGF-β groups than in the TGF-β group (P<0.05). The phosphorylation levels of smad2 and smad3 were remarkably elevated in the TGF-β,30 μmol/L myricetin+TGF-β and 100 μmol/L myricetin+TGF-β groups and the expression of smad4 reduced in the TGF-β group as com-pared with the control group (P<0.05). The levels of smad2,smad3 and smad4 were all significantly decreased in the 30 μmol/L myr-icetin+TGF-β and the 100 μmol/L myricetin+TGF-β groups in comparison with the TGF-β group (P<0.05). Conclusion Myricetin suppresses the activation,proliferation and secretion of cardiac fibroblasts induced by TGF-β via inhibiting the smad signaling pathway.