title: Cytoprotective mechanism of baicalin against endothelial cell damage by peroxynitrite.
abstract: 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.
authors.affiliation: College of Pharmacy, Aging Tissue Bank, Pusan National University, Busan 609-735, Korea.
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Ki Ho
authors.initials: KH
authors.lastname: Cho
authors.forename: Sang Kwan
authors.initials: SK
authors.lastname: Moon
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Kim
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Jae Sue
authors.initials: JS
authors.lastname: Choi
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: 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*
chemical_list: D005419:Flavonoids; D016166:Free Radical Scavengers; D016328:NF-kappa B; D030421:Peroxynitrous Acid; C038044:baicalin