Novel use of silymarin as delayed therapy for acetaminophen-induced acute hepatic injury.

AIM: Recently, we have demonstrated that silymarin has a comparable pharmaceutical activity as Phyllanthus urinaria extract when used to rescue mice from acetaminophen-induced acute liver injury. In the present study, we further compared the therapeutic action of silymarin with N-acetyl cysteine (commonly used in clinical practice for emergency treatments) as a rescuer in mice after administering a lethal dose of acetaminophen for 24 h. METHODS: Acute liver injury was induced in the treatment groups by intraperitoneally administered acetaminophen at a dose of 550 mg/kg body weight on day 1. The control group received an equal volume of physiological saline intraperitoneally. From day 2 to 4, the treatment groups received various doses of silymarin or N-acetyl cysteine orally once daily, while the control group and the acetaminophen group received an equal volume of water orally. The mortality rate was recorded in all groups. On day 5, all mice were sacrificed for examination. RESULTS: Silymarin greatly improved the counteracting effects on mortality rate as compared to N-acetyl cysteine. CONCLUSION: Silymarin should be further considered as an antidote for patients with acetaminopheninduced acute hepatic injury and delayed treatment.

Antiangiogenic activity of a concentrated effective microorganism fermentation extract.

We have previously demonstrated the possible growth inhibitory activity of both first generation of the effective microorganism fermentation extract (EM-X) as well as the second generation (EM-X2) on cancer cell lines in vitro. The possible anti-angiogenic potential of EM-X has not been reported. Herein we show that using the concentrated EM-X, the growth of human umbilical cord endothelial cells (HUCE) was significantly inhibited in vitro. Enzyme linked immunosorbent assay suggested that the concentrated EM-X is able to reduce the level of vascular endothelial growth factor (VEGF) from Hep3B hepatocellular carcinoma (HCC) cells. The conditioned culture medium obtained from the concentrated EM-X incubated Hep3B HCC cells possessed significant antiproliferative effect on the HUCE cells. Moreover, in vivo chick chorioallantoic membrane assay further demonstrated that the concentrated EM-X is able to greatly inhibit the basic fibroblast growth factor induced angiogenesis from chick embryo experiment. We speculate that the anti-cancer potential of this concentrated EM-X involved growth inhibition on cancer cell and antiangiogenic effect on HUCE cells.

Apoptotic potential of the concentrated effective microorganism fermentation extract on human cancer cells.

The effective microorganism fermentation extract (EM-X, the first generation) was claimed to possess strong anti-oxidation property. On the other hand, we have shown that the second generation of the effective microorganism fermentation extract (EM-X2) possessed growth inhibition on human cancer cells involving MDA-MB231 breast cancer and K-562 chronic myelogenous leukaemia cells. Elevation of super oxide dismutase activity from EM-X2 treated cancer cell extract was observed. However, the possible anti-cancer activity of the first generation of the EM-X was not reported. Here we demonstrate that the concentrated form of the EM-X from its original fluid also possess antiproliferation ability together with induction of apoptosis on the human cancer cell lines including Hep3B hepatocellular carcinoma (HCC) and KG1a acute myelogenous leukaemia (AML). Similar effect could also be demonstrated on primary cultured bone marrow samples isolated from patients with AML. Morphological inspection revealed that common apoptotic feature was found on these concentrated EM-X treated cancer cells. Both the anchorage-dependent clonogenicity assay on Hep3B HCC and methyl-cellulose colony formation assay on KG1a cells and bone marrow cells from AML patients further revealed the ability of the concentrated EM-X on reducing their colony formation ability. Incubating KG1a with concentrated EM-X readily induced apoptosis as demonstrated by flow cytometric analysis. Interestingly, few growth inhibition effect of the concentrated EM-X was observed on both the SV40 transformed THLE-2 liver epithelial cells and primary cultured non-malignant haematological disordered bone marrow. Collectively, this concentrated EM-X is effective in inducing cell death and reducing the regeneration potential of both Hep3B HCC and KG1a AML cells in vitro.