Nasoni Maria Gemma, Benedetti Serena, Bargagni Erik, Burattini Sabrina, Osman Riham, Battistelli Michela, Luchetti Francesca
Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy.
Int J Mol Sci. 2025 May 20;26(10):4917. doi: 10.3390/ijms26104917.
Statins, in addition to their main beneficial lipid-lowering effects (lowering cholesterol and LDL levels), have many additional adverse effects. Among them, the most common is skeletal myopathy. Mitochondria not only play a pivotal role in statin-induced adverse skeletal muscle effects but also seem to be involved in the adverse effects of statins on human cardiac function. However, given that similar oxidative phosphorylation pathways are relevant in skeletal and cardiac muscles, whether long-term statin treatment may alter cardiac muscle is currently unknown. Natural products have been widely employed in skeletal muscle disorders thanks to their antioxidant and anti-inflammatory properties. The purpose of this study was to evaluate the effects of a novel phytotherapic formulation (PF) composed of and essential oils, root, and on the human AC16 cell line in an in vitro model of atorvastatin-induced cardiomyopathy. Our results showed that atorvastatin decreased cell viability by approximately 50% and induced ROS production and mitochondrial structural damage. Interestingly, supplementation of cells with PF reduced oxidative stress by 20%, improved mitochondrial reshape and function, and restored the expression of the Nrf2/HO-1/GPX4 axis. These results provide new insights into statin-induced cardiomyopathy and suggest the employment of PF as a promising agent in the recovery of cardiac function.
他汀类药物除了具有主要的有益降脂作用(降低胆固醇和低密度脂蛋白水平)外,还有许多其他不良反应。其中,最常见的是骨骼肌病。线粒体不仅在他汀类药物引起的骨骼肌不良反应中起关键作用,而且似乎还与他汀类药物对人类心脏功能的不良反应有关。然而,鉴于相似的氧化磷酸化途径在骨骼肌和心肌中都相关,长期使用他汀类药物治疗是否会改变心肌目前尚不清楚。天然产物因其抗氧化和抗炎特性已被广泛用于治疗骨骼肌疾病。本研究的目的是在阿托伐他汀诱导的心肌病体外模型中,评估一种由[具体成分1]和[具体成分2]精油、[具体成分3]根以及[具体成分4]组成的新型植物疗法制剂(PF)对人AC16细胞系的影响。我们的结果表明,阿托伐他汀使细胞活力降低了约50%,并诱导了活性氧生成和线粒体结构损伤。有趣的是,用PF处理细胞可使氧化应激降低20%,改善线粒体重塑和功能,并恢复Nrf2/HO-1/GPX4轴的表达。这些结果为他汀类药物诱导的心肌病提供了新的见解,并表明PF有望作为一种恢复心脏功能的药物。