Metabolites of scutellariae radix inhibit injury of endothelial cells in hypoxia device

The effects of the metabolites of Scutellariae Radix (SR), a traditional anti-inflammatory oriental herbal medicine, on hypoxia/reoxygenation (H/R)-induced inflammation and apoptosis of human umbilical vein endothelial cells (HUVECs) were investigated. SR metabolites (SRMs) were prepared from the sulfatase/β-glucuronidase-added serum of SR-decoction-fed rats and examined using highperformance liquid chromatography. HUVECs were put into a mechanical device conditioned with hypoxia (94 %N₂, 5 % CO₂, and 1 %O₂) for 4 h (H4), and then reoxygenation (room air with 5 % CO₂) for 4 h (R4), alone or in the presence of SRMs or vitamin C. Cell adhesion and apoptosis were detected using the enzyme-linked immunosorbent assay. Intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), caspase-3, and heme oxygenase-1 (HO-1) were evaluated using western blotting. COX-2 small hairpin RNA (shRNA) and HO-1 shRNA were used to evaluate the relationship of COX-2 and HO-1 to cell apoptosis. THP-1 adhesion, and ICAM-1 and COX-2 expression increased at H4 and H4/R4, but decreased at H8, and could be ameliorated by SRMs in a dose-dependent manner. Notedly, SRMs effectively attenuated COX-2-mediated cell apoptosis, which was enhanced byHO-1 shRNA, especially atH4/R4 injury. In conclusion, in a hypoxia chamber that mimics the hypoxic condition in acute coronary syndrome, SRMs protected H/Rinduced inflammation and the death of endothelial cells via oxidative stress reduction.