title: Baicalein potently inhibits Rho kinase activity and suppresses actin stress fiber formation in angiotensin II-stimulated H9c2 cells.
abstract: Baicalein is a flavonoid (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran4-one) and an active principle in Scutellaria baicalensis. The present study was performed to investigate the mechanisms underlying the anti-fibrotic effects of baicalein with a focus on Rho kinase (ROCK) inhibition. The effect of baicalein on ROCK activity was analyzed using an immobilized metal affinity for phosphochemicals (IMAP)-based time-resolved fluorescence resonance energy transfer (TR-FRET) assay. The underlying mechanisms of baicalein were examined using angiotensin II-stimulated H9c2 cells. Rho kinase (ROCK1 and ROCK2) studies using IMAP-TR-FRET showed that baicalein possesses potent ROCK inhibitory activity with IC50 values of 6.55 and 2.82 µM, respectively. Pretreatment with baicalein (for 2 h) concentration-dependently decreased the angiotensin II-induced phosphorylation of myosin phosphatase (MYPT) and myosin light chain (MLC). Furthermore, baicalein also concentration-dependently suppressed actin stress fiber formation in angiotensin II-stimulated H9c2 cells. These results suggest that baicalein potently inhibits ROCK and that by so doing it modulates actin stress fiber formation. These anti-fibrotic effects of baicalein explain, at least in part, its pharmacology and mode of action.
authors.affiliation: Bio-Organic Science Division, Korea Research Institute of Chemical Technology, Daejeon 305–343, Republic of Korea.
authors.forename: Kwang-Seok
authors.initials: KS
authors.lastname: Oh
authors.forename: Byung Koo
authors.initials: BK
authors.lastname: Oh
authors.forename: Cheon Ho
authors.initials: CH
authors.lastname: Park
authors.forename: Jihye
authors.initials: J
authors.lastname: Mun
authors.forename: Suk Hyun
authors.initials: SH
authors.lastname: Won
authors.forename: Byung Ho
authors.initials: BH
authors.lastname: Lee
mesh_terms: D000199:Actins / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis / Q000378:metabolism / Q000517:prevention & control; D044950:Flavanones / Q000494:pharmacology* / Q000627:therapeutic use; D020128:Inhibitory Concentration 50; D018994:Myosin Light Chains / Q000378:metabolism; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D031364:Scutellaria baicalensis / Q000737:chemistry*; D022502:Stress Fibers / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000199:Actins; D044950:Flavanones; D018994:Myosin Light Chains; D010936:Plant Extracts; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C006680:baicalein; D054460:rho-Associated Kinases; D043263:Myosin-Light-Chain Phosphatase