Table 3.

Vasculoprotective effects of pomegranate-derived substances or their metabolites, as determined in vitro and in vivo pre-clinical studies.

Vasculoprotective effects	Vasculoprotective substances	References
Induction of paraoxonase 2 and reduction in oxidative stress in isolated macrophages	Punicalagin, gallic acid	Shiner et al., 2007
Attenuation of reactive oxygen species (ROS) generation and prevention of eNOS downregulation induced by oxLDL in HUVECs. Stimulation of vasorelaxation of the rat thoracic aorta ex vivo, via an endothelium-dependent mechanism and through an inhibition of calcium influx	Ellagic acid	Lee et al., 2010; Ou et al., 2010; Yilmaz and Usta, 2013
Suppression of formation of advanced glycation end products (AGEs) in vitro and in mice	Punicalin, punicalagin, ellagic acid, gallic acid	Kumagai et al., 2015
Inhibition of lipid metabolism in adipocytes	Punicalagin, ellagic acid	Les et al., 2017
Antioxidative properties in a cell-based assay in vitro	Urolithins	Bialonska et al., 2009
Inhibition of adhesion of monocytes to endothelial cells, of secretion of a cellular adhesion molecule (VCAM-1) and pro-inflammatory cytokine (IL-6). Decrease in the accumulation of cholesterol in THP-1-derived macrophages	Ellagic acid, urolithin A glucuronide, other urolithins	Gimenez-Bastida et al., 2012; Mele et al., 2016
Attenuation of endothelial dysfunction induced by oxLDL in cultured human artery endothelial cells, partly by counteracting eNOS-dependent decrease in NO production. Reduction in myocardial ischemia/reperfusion injury and myocardial infarct size in vivo	Urolithin A	Han et al., 2016; Tang et al., 2017
Anti-hypertensive effects of sweetie juice in humans	Naringin	Reshef et al., 2005
Amelioration of glucose tolerance and diminishing obesity-related inflammation via activation of PPAR-γ and -α	Puninic acid	Hontecillas et al., 2009