Effect of oxymatrine on murine fulminant hepatitis and hepatocyte apoptosis

To evaluate the protective effects and mechanism of action of oxymatrine (OM) on the experimental fulminant hepatitis (FH) and early hepatocyte apoptosis in mur ine liver tissue Methods Fulminant hepatitis mice were induced by injecting lipopolysaccharide (LPS) intr aperitoneally (ip) in galactosamine (GalN) sensitized mice Two separate experim ents were designed, including saline control group, fulminant hepatitis group an d oxymatrine pretreated group (50?mg/kg, intraperitoneally, bid×3 days) The leve ls of serum tumor necrosis factor alpha (TNFa) in mice from two experiments were determined at 5 hour and 7 5 hour after injecting galactosamine/lipopolysacc haride Mouse liver samples at 5 hour time point were obtained for in situ end labeling (ISEL) staining and ultrastructural observation of apoptotic cells und er transmission electron microscope (TEM) Liver samples at 7 5 hour time poi nt were taken for hematoxylin eosin (HE) staining and immunohistochemical stain ing of Fas and its ligand (FasL) Results As compared with the fulminant hepatitis group, the levels of serum tumor necros is factor alpha in mice from the OM pretreated group at 5 hour and 7 5 hour t ime point were all significantly decreased ( P 【0 05 and P 【0 01 respecti vely) Hepatocyte apoptosis in mice at 5 hour time point was significantly inh ibited ( P 【0 01) Both the degree of liver injury and the degree of Fas and Fas ligand expression in the OM pretreated group were reduced remarkably ( P 【0 01 and 0 05 respectively) when compared with the saline control group Conclusions Oxymatrine protects mice from fulminant hepatitis induced by GalN/LPS and may bl ock hepatocyte apoptosis and subsequent necrosis through downregulating the prod uction of serum tumor necrosis factor alpha and the expression of Fas and Fas li gand in liver tissue

Inhibitory effect of oridonin on proliferation of RPMI8226 cells and the possible underlying mechanism

OBJECTIVE:To observe the effects of oridonin on proliferation and apoptosis of myeloma RPMI8226cells and to investigate the potential underlying mechanisms.METHODS:RPMI8226 cells were treated with various concentrations of oridonin.Cell proliferation was analyzed using the thiazolyl blue tetrazolium bromide method.Ultramicrostructure was observed by transmission electron microscopy.Annexin-V/PI staining and flow cytometry was performed to determine cell apoptosis.Expression of apoptosis-related proteins was evaluated by western blot analysis.RESULTS:Oridonin suppressed the proliferation of RPMI8226 cells and induced apoptosis in a timeand dose-dependent manner.Transmission electron microscopy confirmed apoptotic morphologyupon treatment with 20μmol/L oridonin and western blot revealed decreased expressions of the apoptosis suppressors survivin,Bcl-2 and pro-caspase-3 proteins,and the increased expression of the apoptosis inducer Bax.CONCLUSION:Our results show that oridonin exhibits an inhibitory effect on the proliferation of RPMI8226 cells and induces apoptosis.This is associated with altering the balance between Bcl-2 and Bax protein expressions and decreased survivin and pro-caspase-3 expressions.