Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events.
Taxifolin (TAX) is a typical plant
flavonoid, which has long been used clinically for treatment of cardiovascular and
cerebrovascular diseases. However, very little is known about whether TAX can influence the development of
cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited
angiotensin II (Ang II) induced
hypertrophy and
protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It was demonstrated that TAX prevented pressure overload induced
cardiac hypertrophy in mice, as assessed by ventricular mass/
body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of
ANP, BNP and β-MHC. The excess production of
reactive oxygen species (ROS) played critical role in the development of
cardiac hypertrophy. TAX arrested oxidative stress and decreased the expression of 4-HNE induced by pressure overload. Moreover, TAX negatively modulated TAC-induced phosphorylation of ERK1/2 and JNK1/2. Further studies showed that TAX significantly attenuated left ventricular
fibrosis and
collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. These results demonstrated that TAX could inhibit
cardiac hypertrophy and attenuate ventricular
fibrosis after pressure overload. These beneficial effects were at least through the inhibition of the excess production of ROS, ERK1/2, JNK1/2 and Smad signaling pathways. Therefore, TAX might be a potential candidate for the treatment of
cardiac hypertrophy and
fibrosis.