AIMS Cardiac hypertrophy is one of most important risk factors for cardiovascular mortality. Activation of Wnt/β-catenin signaling pathway is acknowledged to be an important mechanism for pathogenesis of cardiac hypertrophy. Polyphyllin I (PPI), a component in the traditional Chinese medicinal herb, has shown anticancer effect partially via interruption of Wnt/β-catenin signaling pathway. Our aim was to test whether PPI attenuates cardiac hypertrophy. MATERIALS AND METHODS Adult male C57BL/6J mice were subjected to either pressure overload generated by transverse aortic constriction (TAC) or sham surgery (control group). Angiotensin-II (Ang-II) was used to induce cardiomyocyte hypertrophy in vitro. PPI was intraperitoneally administrated daily for 4 weeks after TAC surgery and then cardiac function was determined by echocardiography and histological analysis was performed. KEY FINDINGS PPI significantly ameliorated cardiac dysfunction of mice subjected to TAC. Meanwhile, PPI attenuated TAC induced cardiac hypertrophy indicated by blunted increase in heart mass, cross section area of cardiomyocyte, cardiac fibrosis and expression of hypertrophic biomarkers ANP, BNP and β-MHC. In addition, PPI also ameliorated Ang-II induced cardiomyocyte hypertrophy in vitro. Importantly, PPI decreased protein expression of active β-catenin/total β-catenin, phosphorylation of GSK3β and Wnt target genes c-myc, c-jun, c-fos and cyclin D1 and its anti-hypertrophic effect was blunted by supplementation of Wnt 3a. SIGNIFICANCE Our results suggest that PPI attenuates cardiac dysfunction and attenuate development of pressure over-load induced cardiac hypertrophic via suppressing Wnt/β-catenin signaling pathway. PPI might be a candidate drug for treatment of cardiac hypertrophy.

中文翻译：

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多元茶碱I通过抑制Wnt /β-catenin信号传导途径减轻压力超负荷引起的心脏肥大。

AIMS心脏肥大是心血管疾病死亡的最重要危险因素之一。Wnt /β-catenin信号通路的激活被认为是心肌肥大的重要发病机制。传统中草药中的一种成分Polyphyllin I（PPI）已部分地通过中断Wnt /β-catenin信号通路显示出抗癌作用。我们的目的是测试PPI是否减轻心脏肥大。材料与方法成年雄性C57BL / 6J小鼠经历了由主动脉横向狭窄（TAC）或假手术产生的压力超负荷（对照组）。血管紧张素-II（Ang-II）用于体外诱导心肌肥大。在TAC手术后的4周内每天腹腔注射PPI，然后通过超声心动图确定心脏功能并进行组织学分析。主要发现PPI显着改善了接受TAC的小鼠的心脏功能障碍。同时，PPI减轻了TAC诱导的心脏肥大，其表现为心脏质量，心肌细胞横截面积，心脏纤维化和肥大生物标志物ANP，BNP和β-MHC的表达增加。此外，PPI还改善了Ang-II诱导的心肌肥大。重要的是，PPI降低了活性β-catenin/总β-catenin的蛋白表达，GSK3β和Wnt靶基因c-myc，c-jun，c-fos和cyclin D1的磷酸化，其抗肥厚作用因补充Wnt而减弱3a。意义我们的结果表明，PPI通过抑制Wnt /β-catenin信号传导途径，减轻了心脏功能障碍，并减轻了压力超负荷引起的心肌肥大的发展。PPI可能是治疗心脏肥大的候选药物。