Ankaflavin and Monascin Induce Apoptosis in Activated Hepatic Stellate Cells through Suppression of the Akt/NF-κB/p38 Signaling Pathway

The increased proliferation of activated hepatic stellate cells (HSCs) is associated with hepatic fibrosis and excessive extracellular matrix (ECM)-protein production. We examined the inhibitory effects of the Monascus purpureusfermented metabolites, ankaflavin and monascin (15 and 30 mu M), on the Aid/nuclear factor (NF)-kappa B and p38 mitogen-activated protein kinase (MAPK) signaling pathways in HSC-T6 (activated hepatic stellate cell line). Ankaflavin and monascin (30 mu M) induced apoptosis and significantly inhibited cell growth (cell viabilities: 80.2 +/- 5.43% and 62.8 +/- 8.20%, respectively, versus control cells; P < 0.05). Apoptosis and G1 phase arrest (G1 phase percentages: 76.1 +/- 2.85% and 79.9 +/- 1.80%, respectively, versus control cells 65.9 +/- 4.94%; P < 0.05) correlated with increased p53 and p21 levels and caspase 3 activity and decreased cydin D1 and Bc1-2-family protein levels (P < 0.05, all cases). The apoptotic effects of ankaflavin and monascin were HSC-T6-specific, suggesting their potential in treating liver fibrosis.