OBJECTIVETo evaluate the effect of Ginkgo biloba extract (EGb) on hepatic microcirculation and portal hypertension in CCl4 treated rats.

METHODSTwenty-five male Wistar rats were divided into a blank, a CCl4 treated and a CCl4 plus EGb treated group, and all were treated for 10 weeks. The free portal vein pressures were measured through catheterizations. Hepatic sinusoidal endothelial cells and other parameters of hepatic microcirculation were studied with transmission electron microscopy. The amounts of malondialdehyde (MDA), endothelin (ET-1), platelet-activating factor (PAF), nitric oxide (NO), cNOS and iNOS in the liver tissues were determined.

RESULTSThe portal vein pressure of the CCl4 plus EGb treated group was (7.4 +/- 0.6) mm Hg while the pressure of the CCl4 treated group was (8.7 +/- 0.8) mm Hg. Aggregation of blood cells or microthrombosis in hepatic sinusoids, deposition of collagen in hepatic sinusoids and spaces of Disse, injury of endothelial cells and capillarization of hepatic sinusoid were significantly milder in the EGb group. The amounts of MDA, ET-1, PAF, NO and iNOS were markedly lower in the CCl4 plus EGb treated group than in the CCl4 treated group.

CONCLUSIONThe results demonstrated that EGb can decrease the portal vein pressure and improve hepatic microcirculation in CCl4 treated rats. The mechanisms of this effect may involve its inhibition on ET-1, PAF, lipid peroxidation, and down regulation of the hepatic iNOS and NO expressions.

Animals ; Ginkgo biloba ; Hepatic Veins ; pathology ; Hypertension, Portal ; drug therapy ; physiopathology ; Liver Cirrhosis, Experimental ; chemically induced ; drug therapy ; pathology ; physiopathology ; Male ; Microcirculation ; drug effects ; Plant Extracts ; pharmacology ; Rats ; Rats, Wistar

OBJECTIVETo investigate the effects of Fuzheng Huayu recipe and Huangqi tang on DMN-induced experimental liver cirrhosis in rats and explore the therapeutic characteristics of Buxu herbals on liver cirrhosis.

METHODLiver cirrhosis in rats was induced by intraperitoneally injection of DMN for 4 weeks. Cirrhotic rats were randomly divided into 4 groups: model group, and Fuzheng Huayu recipe group, Huangqi tang group, Fuzheng Huayu recipe combined with Huangqi Tang group. The rats in treatment groups were orally administered with Fuzheng Huayu recipe, Huangqi tang, Fuzheng Huayu recipe combined with Huangqi tang (1:1), respectively. Normal and model control rats were given the equivalent normal saline. The body weight, liver weight and spleen weight were observed when rats were sacrificed. Liver histology was examined by HE staining and Sirius red staining. The liver function parameters including ALT, T. Bil and Alb were determined. The SOD activity and MDA content in liver tissues were also measured. Hepatic hydroxyproline (Hyp) content was determined by Jamall's method. The expression of alpha-SMA was determined by both immunohistochemistry staining and western blot method.

RESULTCompared with normal rats, the serum ALT and T. Bil levels in model rats increased obviously, by contrast, the serum Alb level decreased. There was a significant decline of SOD activity in model rat liver tissue, while the content of MDA and Hyp increased remarkably. A severe deterioration of liver architecture, infiltration of inflammatory cells and deposition of collagen were observed in model rat liver tissue. The expression of alpha-SMA also increased significantly. Compared with model rats, the liver function, lipid peroxidation parameters, Hyp content and liver histology were all improved in the 3 treatment groups. The combined group is better than any single-use group in decreasing collagen deposition and expression of alpha-SMA.

CONCLUSIONFuzheng Huayu recipe, Huangqi tang, Fuzheng Huayu recipe combined with Huangqi tang can attenuate liver fibrosis in DMN induced rats. Fuzheng Huayu recipe combined with Huangqi tang is better than that using alone in decreasing collagen deposition. The mechanism is partially due to the better effect of Fuzheng Huayu recipe combined with Huangqi tang on inhibiting activated HSC.

Animals ; Body Weight ; drug effects ; Dimethylnitrosamine ; adverse effects ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Liver ; drug effects ; enzymology ; Liver Cirrhosis, Experimental ; chemically induced ; drug therapy ; enzymology ; physiopathology ; Organ Size ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism

Magnesium lithospermate B (MLB) is one of the major active components of Salvia miltiorrhizae. The anti-oxidative effects of Salvia miltiorrhizae have been previously reported. The aim of this study was to investigate the effect of purified MLB on hepatic fibrosis in rats and on the fibrogenic responses in hepatic stellate cells (HSCs). Hepatic fibrosis was induced in rats by intraperitoneal thioacetamide (TAA) injections over a period of 8 or 12 weeks. MLB was orally administered daily by gavage tube. Serum AST and ALT levels in TAA + MLB group were significantly lower than those in TAA only group at week 8. Hepatic fibrosis was significantly attenuated in TAA + MLB group than in TAA only group at week 8 or 12. Activation of HSCs was also decreased in TAA + MLB group as compared to TAA only group. Hepatic mRNA expression of alpha-smooth muscle actin (alpha-SMA), TGF-beta1, and collagen alpha1(I) was significantly decreased in TAA + MLB group as compared to TAA only group. Incubation with HSCs and MLB (> or =100 microM) for up to 48 h showed no cytotoxicity. MLB suppressed PDGF-induced HSC proliferation. MLB inhibited NF-kappaB transcriptional activation and monocyte chemotactic protein 1 (MCP-1) production in HSCs. MLB strongly suppressed H2O2-induced reactive oxygen species (ROS) generation in HSCs, and MLB inhibited type I collagen secretion in HSCs. We concluded that MLB has potent antifibrotic effect in TAA-treated cirrhotic rats, and inhibits fibrogenic responses in HSCs. These data suggest that MLB has potential as a novel therapy for hepatic fibrosis.
Actins/genetics/metabolism ; Animals ; Antioxidants/*administration & dosage ; Cell Proliferation/drug effects ; Collagen Type I/genetics/metabolism ; Drugs, Chinese Herbal/*administration & dosage ; Fibrosis/prevention & control ; Hepatic Stellate Cells/*drug effects/metabolism/pathology ; Liver/*drug effects/metabolism/pathology ; Liver Cirrhosis, Experimental/chemically induced/*drug therapy/physiopathology ; Male ; NF-kappa B/metabolism ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Salvia miltiorrhiza/immunology ; Thioacetamide/administration & dosage ; Transcriptional Activation/drug effects