The Activity of Phytotherapic Extracts Combined in a Unique Formulation Alleviates Oxidative Stress and Protects Mitochondria Against Atorvastatin-Induced Cardiomyopathy

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 <i>Curcuma</i> and <i>Boswellia</i> essential oils, <i>Harpagophytum procumbens</i> root, and <i>Bromelain</i> 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.