<i>In vitro</i> mechanism of luteolin suppresses enhanced endothelial permeability

Abstract Luteolin, a flavonoid, has been reported to inhibit the enhanced endothelial permeability in vitro. The purpose of this study was to determine the mechanism of luteolin affected the in vitro suppression of elevated endothelial permeability involves protein kinase C activity and intracellular calcium concentration. The inducer bradykinin was tested using the in vitro vascular permeability assay in endothelial cells obtained from human umbilical vein endothelial cells (HUVECs). Protein kinase C assay test and the intracellular calcium concentration were also determined. Results revealed luteolin (5, 10, and 25 μM) significantly suppressed increased endothelial permeability ( P &lt; 0.001). The increased activity of protein kinase C was significantly suppressed by luteolin at the dose of 5 μM ( P &lt; 0.05), 10 μM ( P &lt; 0.01), and 25 μM ( P &lt; 0.01). The increased concentration of intracellular calcium was significantly suppressed by luteolin at the dose of 10 μM ( P &lt; 0.01) and 25 μM ( P &lt; 0.001). Collectively, these results showed luteolin suppressed the activity of protein kinase C and suppressed the increased concentration of intracellular calcium when HUVECs were induced by bradykinin, leading to the suppression of increased endothelial permeability as the nitric oxide-cyclic guanosine monophosphate (NO-cGMP ) pathway was being inactivated. This may explain the pharmacologic properties of luteolin, which is anti-inflammatory, antioxidant, and neuroprotective. These results also revealed the potential use of luteolin in treating many other diseases involve endothelial permeability.