Macrophage polarization by potential nutraceutical compounds: A strategic approach to counteract inflammation in atherosclerosis

Chronic inflammation represents a main event in the onset and progression of atherosclerosis and is closely associated with oxidative stress in a sort of vicious circle that amplifies and sustains all stages of the disease. Key players of atherosclerosis are monocytes/macrophages. According to their pro- or anti-inflammatory phenotype and biological functions, lesional macrophages can release various mediators and enzymes, which in turn contribute to plaque progression and destabilization or, alternatively, lead to its resolution. Among the factors connected to atherosclerotic disease, lipid species carried by low density lipoproteins and pro-oxidant stimuli strongly promote inflammatory events in the vasculature, also by modulating the macrophage phenotyping. Therapies specifically aimed to balance macrophage inflammatory state are increasingly considered as powerful tools to counteract plaque formation and destabilization. In this connection, several molecules of natural origin have been recognized to be active mediators of diverse metabolic and signaling pathways regulating lipid homeostasis, redox state, and inflammation; they are, thus, considered as promising candidates to modulate macrophage responsiveness to pro-atherogenic stimuli. The current knowledge of the capability of nutraceuticals to target macrophage polarization and to counteract atherosclerotic lesion progression, based mainly on in vitro investigation, is summarized in the present review.