Functional compounds oleuropein and hydroxytyrosol in olive leaves attenuate chronic kidney disease-induced muscle atrophy

<h2>Abstract</h2> Chronic kidney disease (CKD) progression is a risk factor for the loss of muscle mass and strength and heart disease, leading to increased mortality. Hydroxytyrosol (HT) and its precursor oleuropein (OLE), the major phenolic compounds in olive leaves, were found to exert many pharmacological properties, including anticancer, antidiabetic, and anti-inflammatory effects, and offer various health benefits to the organism. In this study, the effects of HT and OLE on cultured myoblast C2C12 cells exposed to the uremic toxin indoxyl sulfate and on adenine and Indoxyl sulfate (IS) -induced CKD mice, respectively, were investigated. OLE significantly suppressed CKD development and attenuated nephropathic muscle atrophy by reducing oxidative stress and promoting muscle protein synthesis and autophagy. HT exhibited similar effects in cultured myoblast cells as OLE did <i>in vivo</i>, suggesting a shared mechanism of action in mitigating muscle atrophy. These findings support the potential role of HT and OLE in preventing and attenuating CKD-induced muscle atrophy. Furthermore, our results highlight the potential of food-derived compounds as promising candidates for novel preventive and therapeutic approaches against muscle wasting in CKD.