Mechanistic Insights on Cardioprotective Properties of Ursolic Acid: Regulation of Mitochondrial and Non-mitochondrial Pathways

Ursolic acid, a natural pentacyclic triterpenoid compound, has been shown to have significant cardioprotective effects in various preclinical studies. This article reviews the various mechanisms by which ursolic acid achieves its cardioprotective effects, highlighting its potent anti-oxidant, anti-inflammatory, and anti- apoptotic properties. Ursolic acid upregulates anti-oxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx), effectively reducing oxidative stress, thereby decreasing reactive oxygen species (ROS) and improving lipid peroxidation levels. Furthermore, ursolic acid downregulates pro-inflammatory cytokines and inhibits key inflammatory pathways, such as nuclear factor kappa B (NF-κB), which results in its anti-inflammatory effects. These actions help in protecting cardiac tissues from acute and chronic inflammation. Ursolic acid also promotes mitochondrial function and energy metabolism by enhancing mitochondrial biogenesis and reducing dysfunction, which is critical during ischemia-reperfusion (I/R) injury. Additionally, ursolic acid influences multiple molecular pathways, including B-cell leukemia/lymphoma 2 protein (Bcl- 2)/Bcl-2 associated x-protein (Bax), miR-21/extracellular signal-regulated kinase (ERK), and phosphoinositide 3-kinase (PI₃K)/protein kinase B (Akt), to reduce cardiomyocyte apoptosis. Collectively, these properties make ursolic acid a promising therapeutic agent for cardiovascular diseases (CVDs), warranting further research and clinical trials to harness its potential fully.