Yongying Shi^{1, 2}, Aijun Liu³, Junjiang Lu⁴, Guangyuan Chen¹, Shiming Liu^{2, 5}, Minsheng Chen⁶, Chengfeng Luo^{2, 5,}

Recent studies have suggested that puerarin may attenuate cardiac hypertrophy in mice; however, the underlying mechanism remains unclear. To investigate the role of puerarin in transforming growth factor beta 1 (TGF-β₁)-induced cardiac hypertrophy and the underlying mechanisms. Primary neonatal rat cardiomyocytes (NRCMs) were isolated form the heart of neonatal Wistar rats (1- to 2-day-old) and treated with different doses of puerarin (0,0.1,1or 5 g/L) in the presence of TGF-β₁ (3 μg/L) to investigate the effect of puerarin on TGF-β₁-induced hypertrophic changes and Smad protein alterations. RNA and protein biosynthesis in NRCMs were evaluated by synpropidium iodide staining and [³H]-leucine incorporation, respectively. Gene expression alterations were determined using quantitative real-time PCR and Western blot analysis. Compared with Smad2 knockdown, puerarin treatment (1 g/L) exhibited similar but stronger effects in abrogating TGF-β₁-induced RNA and protein biosynthesis as well as fetal gene upregulation in NRCMs. In addition, puerarin treatment (1 g/L) could remarkably reverse TGF-β₁-induced upregulation of Smad protein expression in NRCMs, suggesting that deactivation of the Smad signaling is possibly involved in the antihypertrophic role of puerarin. Our data suggest that puerarin may protect cardiomyoctyes against TGF-β₁-induced hypertrophic responses and Smad signaling activation, providing basic dosage information and possible targets for puerarin treatment in animal models.

cardiomyocyte hypertrophy, transforming growth factor-β₁, the Smad signaling