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 path- ways 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 formula- tion (PF) composed of Curcuma and Boswellia essential oils, Harpagophytum procumbens root, and Bromelain 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.