Enbucrilate ; adverse effects ; therapeutic use ; Female ; Humans ; Hypertension, Portal ; diagnosis ; etiology ; Liver Cirrhosis, Biliary ; drug therapy ; Middle Aged ; Pulmonary Embolism ; chemically induced ; diagnosis ; Sepsis ; chemically induced ; etiology

OBJECTIVETo observe the therapeutic effect of Xiaozheng Rongmu Powder (XRP) for the treatment of progressive CCl4-induced liver cirrhosis in rats.

METHODSRat liver cirrhosis model was established by subcutaneous injection of 50% CCl4-olive oil 2 mL/kg twice a week for 12 weeks. Experimental rats were divided into the control group treated by saline and the two treatment groups, treated with XRP and Xiaochaihu Decoction, respectively, with the treatment starting from the 9th week of modeling. Rats were sacrificed at the terminal of experiment, the death rate, character of ascites, liver histological changes, liver function, mRNA expression of hepatocyte mitosis and the liver fibrosis associated markers in rats were observed.

RESULTSAt the end of the 8th week of modeling, serum levels of ALT, AST and TBil were increased, and Alb decreased significantly in rats (P < 0.01), cirrhosis formation with ascites could be seen in all rats. Meantime, levels of vascular smooth muscle alpha-actin, transforming growth factor-beta1, collagen I A2, tumor necrosis factor-alpha, tissue inhibitor of melalloproteinase-1 mRNA increased, while matrix melalloproteinase-13 mRNA were decreased significantly (P < 0.01), with visible liver proliferation to some extents. Further changes of above-mentioned abnormalities and clear suppression of hepatocytes mitosis were found in the modeled rats at the end of the 12th week. As compared to those occurred in the control group, changes in the XRP treated group were significantly milder at the corresponding duration, and clearly active hepatocytes mitosis was shown.

CONCLUSIONXRP, a Chinese drug with the effect of dissolving phlegm, removing stasis and supplementing qi, could reverse the progress of cirrhosis formation induced by CCl4, and it brings potential new hope for the treatment of advanced cirrhosis by Chinese medicine.

Animals ; Carbon Tetrachloride ; Drugs, Chinese Herbal ; therapeutic use ; Liver Cirrhosis, Experimental ; chemically induced ; drug therapy ; Male ; Phytotherapy ; Rats ; Rats, Wistar

OBJECTIVES: To observe the preventive and therapeutic action of Yuyin Ruangan Granule (YRG, Traditional Chinese Medicine) in hepatic fibrosis rats model and its effect on transforming growth factor-β1 (TGF-β1) expression. METHODS: The Wistar rats were randomly divided into 6 group (=10), and the model of hepatic fibrosis rats was established by subcutaneous injected with carbon tetrachloride (CCL4), fed on high-fat diet and 20% ethanol for 6 weeks, to survey the effect and mechanism of YRG preventing hypatic fibrosis by detecting liver function (the activity of alanine aminotransferase(ALT), aspartate aminotransferase(AST), etc.) of liver fibrosis rats, liver fibrosis indicators (hyaluronic acid, Ⅲ procollagen, type IV collagen, laminin and hepatic pathology, etc.), and TGF-β1 expression in liver tissue after 6 weeks treated with YRG through intragastric administration (q. d.). RESULTS: At the 7 week, fibrotic lesions appears distinctly in liver tissue of model group compared with control group (<0.01), YRG of 6.2~28.8 g/kg could significantly decrease hepatic index, ALT and AST activities, content of hyaluronic acid(HA), Ⅲ procollagen (PCⅢ), type Ⅳ collagen(C-Ⅳ), laminin (LN) in serum, relieve liver fibrosis pathological changes and inhibit TGF-β1 expression in fibrotic liver tissue (<0.05, <0.01). CONCLUSIONS YRG has significantly preventive effects on liver fibrosis rats model, and it may be one of its mechanisms to inhibit expression of TGF-β1.
Animals ; Carbon Tetrachloride ; Drugs, Chinese Herbal ; pharmacology ; Liver ; drug effects ; metabolism ; Liver Cirrhosis ; chemically induced ; drug therapy ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Transforming Growth Factor beta1 ; metabolism

Animals ; Anthraquinones ; therapeutic use ; Carbon Tetrachloride ; Carbon Tetrachloride Poisoning ; Drug Therapy, Combination ; Liver Cirrhosis, Experimental ; chemically induced ; drug therapy ; Male ; Pyrazines ; therapeutic use ; Rats ; Rats, Wistar

OBJECTIVETo optimize a compound prescription for treatment of liver fibrosis with an improved therapeutic effect and low toxicity.

METHODSIn rat models of liver fibrosis induced by thioacetamide (TAA), the optimized prescription was screened based on a uniform design with 2-factor 5-level table using Uniform Design 3.0 software and tested using liver content of Hyp as the screening index. To verify the efficacy of the optimized prescription, the rat models of liver fibrosis were randomized into normal control group, model group, colchicine group and optimized prescription group, and the changes of hepatic Hyp content, serum HA, ALT, AST, and ALB levels, and the pathology liver fibrosis were observed after corresponding treatments.

RESULTSThe optimized prescription, which contained 70 mg/kg glycyrrhizin and 70 mg/kg matrine, showed a significant therapeutic effect against liver fibrosis in rats (Plt;0.05), and the effect was equivalent to that of colchicine (P>0.05).

CONCLUSIONUniform design is a valuable method in prescription optimization. The optimized compound prescription of matrine and glycyrrhizin has a significant effect in inhibiting liver fibrosis.

Alkaloids ; administration & dosage ; Animals ; Drug Therapy, Combination ; Female ; Glycyrrhizic Acid ; administration & dosage ; Liver Cirrhosis ; chemically induced ; drug therapy ; Male ; Phytotherapy ; Quinolizines ; administration & dosage ; Rats ; Rats, Sprague-Dawley ; Thioacetamide

BACKGROUND: The current study aimed to investigate the hepatoprotective effects of Sasa veitchii extract (SE) on carbon tetrachloride (CCl)-induced liver fibrosis in mice. METHODS: Male C57BL/6J mice were intraperitoneally injected with CCl dissolved in olive oil (1 g/kg) twice per week for 8 weeks. SE (0.1 mL) was administered orally once per day throughout the study, and body weight was measured weekly. Seventy-two hours after the final CCl injection, mice were euthanized and plasma samples were collected. The liver and kidneys were collected and weighed. RESULTS: CCl administration increased liver weight, decreased body weight, elevated plasma alanine aminotransferase, and aspartate aminotransferase and increased liver oxidative stress (malondialdehyde and glutathione). These increases were attenuated by SE treatment. Overexpression of tumor necrosis factor-α was also reversed following SE treatment. Furthermore, CCl-induced increases in α-smooth muscle actin, a marker for hepatic fibrosis, were attenuated in mice treated with SE. Moreover, SE inhibited CCl-induced nuclear translocation of hepatic nuclear factor kappa B (NF-κB) p65 and phosphorylation of mitogen-activated protein kinase (MAPK). CONCLUSION These results suggested that SE prevented CCl-induced hepatic fibrosis by inhibiting the MAPK and NF-κB signaling pathways.
Animals ; Carbon Tetrachloride ; toxicity ; Liver Cirrhosis ; chemically induced ; drug therapy ; Male ; Mice ; Mice, Inbred C57BL ; Plant Extracts ; pharmacology ; Protective Agents ; pharmacology ; Random Allocation ; Sasa ; chemistry

OBJECTIVETo investigate the therapeutic effects of peptide YY against hepatic fibrosis in rats and explore the possible mechanism.

METHODRat models of hepatic fibrosis were established with a subcutaneous injection of carbon tetrachloride and randomized into normal control group, model group, peptide YY (PYY)-treated group, octreotide-treated group, and interferon gamma-treated group. Serum levels of the hepatic function indices and hepatic fibrotic index were detected, and the hepatic fibrosis grade was assessed using HE staining. The expression of transforming growth factor beta1 (TGFbeta1) were determined with immunohistochemical staining method.

RESULTSThe rats in PYY-treated group showed significantly different serum levels of TBIL, HA and LN from the rats in the model group (P<0.05). PYY significantly reduced hepatic fibrosis scores and lowered TGFbeta1 expression as compared with the model group.

CONCLUSIONSPYY can down-regulate TGFbeta1 expression to inhibit the development of hepatic fibrosis with comparable efficacy with interferon gamma and octreotide.

Animals ; Carbon Tetrachloride ; Immunohistochemistry ; Liver Cirrhosis, Experimental ; chemically induced ; drug therapy ; metabolism ; Male ; Peptide YY ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; biosynthesis

OBJECTIVETo investigate the recipe-based pathogenesis and effects of Xiayuxue Decoction (XD), Yinchenhao Decoction (YcD), Yiguanjian Decoction (YgD) and Huangqi Decoction (HD) on carbon tetrachloride (CCl4) induced liver cirrhosis formation in rats on the basis of the recognition of basic pathogenesis of liver cirrhosis in TCM and train of thoughts of detecting the TCM syndrome by recipe.

METHODSModel rats of liver cirrhosis were established by subcutaneous injecting of 100% CCl4 3ml/kg followed by 50% CCl4 olive solution 2ml/kg, twice a week for 12 weeks. They were randomly divided into the model group, the XD treated group, the YcD treated group, the YgD treated group and the HD treated group. Rats in the three treated group received the treatment starting from the 9th week of modeling with the corresponding decoctions. All animals were sacrificed by the end of the 12th week, and their hepatic function, liver pathological changes and hydroxyproline (Hyp) content of hepatic tissue were detected.

RESULTS(1) Typical chronic liver injury and fibrosis became evident in the model rat at the 8th week and cirrhosis came into being at the 12th week. (2) Compared with the rats in the model group, hepatic pathological changes were alleviated significantly, content of Hyp in hepatic tissue was decreased markedly and hepatic function improved remarkably in the XD group and YgD group. The improvement in the XD group was superior to that in the YgD group, while the serum albumin level elevated more significant in the YgD group.

CONCLUSIONThe main pathological changes during CCl4 induced liver cirrhosis formation in rats is the rapid hyperplasia of hepatic fibrous connective tissue and obstruction of collaterals by blood stasis, thus induced reconstruction of the tissue structure, which could be treated with XD effectively, while the severe injury of liver parenchyma in this phase is another pathological change of Gan-yin deficiency syndrome, which could be effectively treated with YgD by its Yin-nourishing action.

Animals ; Carbon Tetrachloride ; Diagnosis, Differential ; Drugs, Chinese Herbal ; therapeutic use ; Hydroxyproline ; metabolism ; Liver ; drug effects ; metabolism ; pathology ; Liver Cirrhosis, Experimental ; chemically induced ; diagnosis ; drug therapy ; Male ; Medicine, Chinese Traditional ; Phytotherapy ; Random Allocation ; Rats ; Rats, Wistar ; Yin Deficiency ; drug therapy

OBJECTIVETo observe the effects of Danggui Buxue Decoction (DBD) on liver fibrosis and to explore its mechanism related to hepatic lipid peroxidation in rats.

METHODSLiver fibrosis model was established in 28 rats by the combination of injecting carbon tetrachloride (CCl4) subcutaneously and feeding high lipid and low protein diet. The model rats were randomly divided into 2 groups, the model group (n = 14) and the treated group (n = 14). Besides, a normal group was set up with 10 normal rats. For the treated group, rats were administered with DBD at a dosage of 6 g/kg body weight once a day by gastrogavage starting from the day of modeling for 6 successive weeks and to the control group, equal volume of normal saline was administered instead. The inflammation and fatty degeneration in rat liver tissues were examined with HE staining; the collagen deposition observed with sirius red; the liver function including serum level of alanine transaminase (ALT), aspartate aminotransferase (AST), albumin (Alb) and total bilirubin (TBil) were determined using corresponding test kits; the hepatic lipid peroxidation indexes, including triglyceride (TG), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by biochemical methods; the hepatic hydroxyproline (Hyp) content was detected with Jamall's method and the expression of collagen type I was analyzed by Western blotting.

RESULTSCompared with those in the normal rats, serum ALT, AST, TBil level, TG and MDA content remarkablely increased, level of Alb and SOD activity decreased, and hepatic fatty degeneration and collagen pathological deposition in liver was more obvious in the model rats (all P < 0.05). While in the DBD group, the hepatic fatty degeneration and collagen deposition were significantly improved, changes of all the above-mentioned indexes were significantly reversed (P <0.05).

CONCLUSIONDBD has a good antagonist effect against experimental liver fibrosis, and its mechanism may be related to the anti-lipid peroxidation injury effect.

Animals ; Carbon Tetrachloride ; Collagen ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Lipid Peroxidation ; drug effects ; Liver ; drug effects ; metabolism ; pathology ; Liver Cirrhosis ; chemically induced ; drug therapy ; metabolism ; Male ; Phytotherapy ; Random Allocation ; Rats ; Rats, Wistar

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