Cytoprotective mechanism of baicalin against endothelial cell damage by peroxynitrite.
To evaluate the mechanism responsible for the cytoprotective effects of baicalin, an antioxidant flavonoid isolated from Scutellaria baicalensis, we investigated its effects against peroxynitrite (ONOO-)-induced endothelial cell (EC) damage. Baicalin showed efficient antioxidative actions by its ability to scavenge ONOO and inhibit ONOO(-)-mediated nitrotyrosine formation in vitro. Using an EC (YPEN-1) culture system, baicalin exhibited cytoprotective effects against cell death by ONOO- that was induced exogenously with tert-butyl hydroperoxide (t-BHP) in the YPEN-1 model. Baicalin was also found to reduce the intracellular precursors of ONOO-, NO* and O2(-) in the t-BHP-treated ECs. Evidence from Western blotting further revealed down-regulated expressions of iNOS and COX2, endogenous sources of NO* and O2(-) by baicalin treatment. In addition, pre-incubation of baicalin with EC suppressed t-BHP-induced nuclear factor kappa-B binding activity as determined by the transfection assay and Western blot analysis, further indicating baicalin's inhibition of iNOS and COX-2 expression. Based on the present data, we propose that baicalin scavenges ONOO- and protects cells against injury. Based on these data, it was concluded that baicalin is potentially a useful antioxidant against ONOO- and NO* and an inhibitor of iNOS and COX-2.
Kim
Dae Hyun
DH
College of Pharmacy, Aging Tissue Bank, Pusan National University, Busan 609-735, Korea.
Cho
Ki Ho
KH
Moon
Sang Kwan
SK
Kim
Young Suk
YS
Kim
Dong Hyun
DH
Choi
Jae Sue
JS
Chung
Hae Young
HY
D002460:Cell Line; D019610:Cytoprotection / Q000187:drug effects*; D004727:Endothelium / Q000166:cytology / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000494:pharmacology*
D005419:Flavonoids; D016166:Free Radical Scavengers; D016328:NF-kappa B; D030421:Peroxynitrous Acid; C038044:baicalin