In addition to high plasma glucose, increased levels of trimethylamine N-oxide (TMAO) have been found in obese subjects, where are considered as a novel risk factor for cardiovascular diseases. The present study aimed to investigate the effect of a novel nutraceutical formulation based on grape polyphenols (registered as Taurisolo®) in counteracting TMAO- and high glucose (HG)-induced cytotoxicity in cardiomyoblast H9c2 cells. Cell damage was induced with HG (HG-H9c2) and HG+TMAO (THG-H9c2); both experimental cell models were, thus, incubated for 72 h in the presence or absence of Taurisolo®. It was observed that Taurisolo® significantly increased the cell viability and reduced lactate dehydrogenase and aspartate transaminase release in both HG- and THG-H9c2 cells. Additionally, through its antioxidant activity, Taurisolo® modulated cell proliferation via ERK activation in THG-H9c2. Furthermore, Taurisolo® was able to induce autophagic process via increasing the expression of LC3II, a protein marker involved in formation of autophagosome and ex novo synthesis of sphingomyelin, ceramides, and their metabolites both in HG- and THG-H9c2 cells. Finally, Taurisolo® reduced hypertrophy and induced differentiation of HG-H9C2 cells into cardiomyocyte-like cells. These data suggest that Taurisolo® counteracts the toxicity induced by TMAO and HG concentrations increasing autophagic process and activating de novo sphingolipid synthesis, resulting in a morphological cell remodeling. In conclusion, our results allow speculating that Taurisolo®, combined with energy restriction, may represent a useful nutraceutical approach for prevention of cardiomyopathy in obese subjects.

中文翻译：

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Taurisolo®在新生糖鞘脂合成中对高糖和三甲胺N-氧化物处理的心肌成肌细胞H9c2的心脏保护作用

除了高血浆葡萄糖外，在肥胖的受试者中还发现了三甲胺N-氧化物（TMAO）含量的增加，肥胖的受试者被认为是心血管疾病的新危险因素。本研究旨在研究基于葡萄多酚（注册为Taurisolo®）的新型营养制剂在抵消成肌细胞H9c2细胞中TMAO和高葡萄糖（HG）诱导的细胞毒性中的作用。HG（HG-H9c2）和HG + TMAO（THG-H9c2）诱导细胞损伤。因此，在有或没有Taurisolo®的情况下，将两种实验细胞模型孵育72小时。观察到Taurisolo®在HG-和THG-H9c2细胞中均显着提高了细胞活力并减少了乳酸脱氢酶和天冬氨酸转氨酶的释放。此外，通过其抗氧化活性，通过THG-H9c2中的ERK激活。此外，Taurisolo®能够诱导自噬过程通过增加LC3II，涉及自噬体形成和的蛋白质标志物的表达Novo生产鞘磷脂的合成，神经酰胺，以及它们二者在HG-和THG-H9c2细胞代谢物。最后，Taurisolo®减少了肥大，并诱导HG-H9C2细胞分化为心肌样细胞。这些数据表明，Taurisolo®可抵消TMAO和HG浓度诱导的毒性，从而增加自噬过程并重新激活鞘脂合成，导致形态细胞重塑。总之，我们的结果可以推测Taurisolo®与能量限制相结合可能是预防肥胖受试者心肌病的一种有用的营养保健方法。