Suppression of activation or fibrogenesis and induction of apoptosis, in hepatic stellate cells (HSCs) have been proposed as therapeutic strategies against liver fibrosis. Curcumin, an active compound isolated from yellow curry pigment of turmeric (Curcuma longa Linn), has been demonstrated to be an effective anti-inflammatory and antioxidant compound. In this study, we investigated the in vitro antifibrogenic effects of curcumin on HSCs at the concentration range of (1-40 microM). A cell line of rat HSCs (HSC-T6) was stimulated with transforming growth factor-beta1 (TGF-beta1). The inhibitory effects of curcumin (1.25 approximately 10 microM) on fibrosis-related markers including alpha-smooth muscle actin (alpha-SMA) and collagen were assessed. In addition, the induction effects of curcumin (20 approximately 40 microM) on apoptosis in HSC-T6 cells were also assessed by Hoechst and propidium iodide stains. Curcumin (1.25 approximately 10 microM) concentration-dependently suppressed TGF-beta1-induced alpha-SMA expression and collagen deposition in HSC-T6 cells, without cytotoxicity. Whereas, higher concentrations of curcumin (20 approximately 40 microM) induced cell apoptosis and cytochrome c release in HSC-T6 cells. Our results suggest that curcumin exerted antifibrotic effects, possibly through two different mechanisms depending on its concentrations. At lower concentrations (1.25 approximately 10 microM), curcumin exerted antifibrogenic effects, whereas at higher concentrations (20 approximately 40 microM), curcumin exerted induction of apoptosis in HSCs.
Copyright 2009 John Wiley & Sons, Ltd.