Oxymatrine liposome attenuates hepatic fibrosis via targeting hepatic stellate cells

Figure 1 Oxymatrine liposomes attenuated hepatic fibrosis and improved collagen deposition. A: Representative images of liver treated with oxymatrine (OM) in different liposomal formulations in rats with CCl₄-induced hepatic fibrosis. Liver tissues were obtained at 4 wk after treatment and stained with HE; B: Representative histological images of liver treated with OM in different liposomal formulations in rats with CCl₄-induced hepatic fibrosis. Liver tissues were obtained at 4 wk after treatment and stained with Masson stain (original magnification × 100). HE: Hematoxylin and eosin.

Figure 2 Oxymatrine liposomes induced apoptosis in hepatic stellate cells in vitro. A: Inhibitory effect of oxymatrine (OM) on hepatic stellate cell (HSC) viability in vitro. HSCs were isolated and treated with OM in different liposomal formulations. Cell viability was determined using MTT assay; B: Electron micrograph of untreated HSCs demonstrates the normal structure of HSCs. OM-liposome-treated (24 h) HSCs had morphological features of apoptosis: cell shrinkage and apoptotic body formation. OM-RGD-liposome-treated HSCs showed typical morphological features of apoptosis: cell shrinkage and apoptotic body formation. RGD-liposome-treated HSCs showed normal structure; C: Cell cycle analysis after induction of apoptosis in HSCs by OM via flow cytometry. The cells were incubated with different formulation of OM for 24 h, and stained with PI. MTT: 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide; RGD: Arg-Gly-Asp; PI: Propidium iodide; DI: DNA grading index.

Figure 3 Oxymatrine liposomes inhibited fibrosis-related gene expression. The expression of fibrosis-related gene, such as MMP-2, TIMP-1 and collagen I was evaluated by real-time polymerase chain reaction. ^aP < 0.05 vs normal; ^cP < 0.05 vs CCl₄-induced heaptic fibrosis; ^eP < 0.05 vs oxymatrine liposomes. MMP: Matrix metallopeptidase; TIMP: Tissue inhibitor of metalloproteinase; OM: Oxymatrine; RGD: Arg-Gly-Asp.

Figure 4 Representative fluorescein isothiocyanate hepatic stellate cells in rat hepatic tissue treated with oxymatrine liposomes and oxymatrine-Arg-Gly-Asp liposomes (original magnification × 200). OM: Oxymatrine; RGD: Arg-Gly-Asp.