The therapeutic goal in liver fibrosis is the reversal of fibrosis and the selective clearance by apoptosis of hepatic stellate cells (HSCs), which play a central role in liver fibrogenesis.
METHODS AND RESULTS:
In this study, the apoptotic effect of wogonin, oroxylin A,
2',5,6',7-Tetrahydroxyflavone, skullcapflavone I, and baicalein, isolated from the dried root of Scutellaria baicalensis, was investigated in activated rat HSCs, T-HSC/Cl-6 cells transformed with the Simian virus 40. Among the isolated compounds, skullcapflavone I (20 microM for 24 h) significantly induced apoptosis in activated rat HSCs while there was no change in the cell viability of hepatocytes. Skullcapflavone I increased caspase-3 and -9 activities accompanied by the proteolytic cleavage of poly(ADP-ribose) polymerase. Specific inhibitors of caspase-3 and caspase-9 prevented the apoptotic process induced by skullcapflavone I.
CONCLUSIONS:
From these results, skullcapflavone I from S. baicalensis selectively induced apoptosis in T-HSC/Cl-6 cells via caspase-3 and caspase-9 activation. |
