Puerarin Attenuates Cardiac Hypertrophy Partly Through Increasing Mir-15b/195 Expression and Suppressing Non-Canonical Transforming Growth Factor Beta (Tgf beta) Signal Pathway

Background: Previous studies demonstrated that puerarin has therapeutic effects on cardiac hypertrophy. This study aimed to explore whether the effect of puerarin on attenuating cardiac hypertrophy is related to regulation of microRNAs (miRNAs) and the transforming growth factor beta (TGF beta) signal pathway. Material/Methods: The therapeutic effect of puerarin was assessed using an angiotensin (Ang) II-induced heart hypertrophy model in mice. The primary cardiomyocytes were used as an in vitro model. MiR-15 family expression was quantified using qRT-PCR analysis. The expression of the genes involved in canonical and non-canonical TGF beta signal pathways was measured using qRT-PCR and Western blot analysis. In vitro cardiac hypertrophic features were assessed by quantifying cardiac hypertrophic genes and measurement of cell surface, protein synthesis, and total protein content. Results: Puerarin attenuated cardiac hypertrophy and increased miR-15b and miR-195 expression in the mouse cardiac hypertrophy model and in primary cardiomyocytes. It suppressed both canonical and non-canonical TGF beta signal pathways, partially through miR-15b and miR-195. Puerarin reduced mRNA expression of cardiac hypertrophic genes, reduced cell surface area, and lowered the rate of protein synthesis and the total protein content induced by Ang II. Knockdown of endogenous miR-15b and miR-195 partly abrogated these effects. Knockdown of endogenous p38, but not Smad2/3/4, presented similar effects as miR-15b. Conclusions: Puerarin administration enhances miR-15b and miR-195 expression in an Ang II-induced cardiac hypertrophy model, through which it suppresses both canonical and non-canonical TGF beta signal pathways at the same time. However, the effect of puerarin on attenuating cardiac hypertrophy is mainly through the non-canonical TGF beta pathway.