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

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

BACKGROUND/AIMS: The development of therapeutic strategies for the treatment of cirrhosis has become an important focus for basic and clinical researchers. Adrenergic receptor antagonists have been evaluated as antifibrotic drugs in rodent models of carbon tetrachloride (CCl4)-induced cirrhosis. The aim of the present study was to evaluate the effects of carvedilol and doxazosin on fibrosis/cirrhosis in a hamster animal model. METHODS: Cirrhotic-induced hamsters were treated by daily administration of carvedilol and doxazosin for 6 weeks. Hepatic function and histological evaluation were conducted by measuring biochemical markers, including total bilirubin, aspartate aminotransferase, alanine aminotransferase and albumin, and liver tissue slices. Additionally, transforming growth factor beta (TGF-beta) immunohistochemistry was analyzed. RESULTS: Biochemical markers revealed that hepatic function was restored after treatment with doxazosin and carvedilol. Histological evaluation showed a decrease in collagen type I deposits and TGF-beta-secreting cells. CONCLUSIONS: Taken together, these results suggest that the decrease in collagen type I following treatment with doxazosin or carvedilol is achieved by decreasing the profibrotic activities of TGF-beta via the blockage of alpha1- and beta-adrenergic receptor. Consequently, a diminution of fibrotic tissue in the CCl4-induced model of cirrhosis is achieved.
Adrenergic alpha-1 Receptor Antagonists/*pharmacology ; Alanine Transaminase/blood ; Animals ; Aspartate Aminotransferases/blood ; Bilirubin/blood ; Carbazoles/*pharmacology ; Carbon Tetrachloride ; Collagen Type I/drug effects/metabolism ; Cricetinae ; Doxazosin/*pharmacology ; Liver/metabolism/pathology ; Liver Cirrhosis/blood/chemically induced/*drug therapy ; Liver Function Tests ; Propanolamines/*pharmacology ; Serum Albumin/analysis ; Transforming Growth Factor beta/blood/*drug effects

This study is designed to explore the possible effects of Hemerocallis citrina baroni flavonids (HCBF) on liver fibrosis induced by CCl4 in rats. The liver fibrosis model was induced by CCl4, and HCBF were administered by gastric perfusion at 25 and 50 mg x kg(-1) qd for 50 days, while the contents of alanine transaminase (ALT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), superoxide dismutase (SOD), maleic dialdehyde (MDA) and transforming growth factor-β1 (TGF-β1) were measured and the contents of PINP were measured in liver tissue, and the expression of TGF-β1 were observed by immunohistochemisty and Western blot. The pathological changes of liver tissue were examined by HE. The results showed that HCBF (25, 50 mg x kg(-1)) improved the liver function significantly through reducing the level of ALT, AST, GGT and ALP (P < 0.05 or P < 0.01), and increasing the content of SOD (P < 0.01), while reducing the content of MDA (P < 0.05 or P < 0.01), the expression of TGF-β1 (P < 0.05) and the content of PINP (P < 0.05). The results suggest that HCBF (25, 50 mg x kg(-1)) may inhibit the liver injury induced by CCl4 by decreasing the oxidative stress.
Alanine Transaminase ; metabolism ; Alkaline Phosphatase ; metabolism ; Animals ; Aspartate Aminotransferases ; metabolism ; Carbon Tetrachloride ; Drugs, Chinese Herbal ; pharmacology ; Flavonoids ; pharmacology ; Hemerocallis ; chemistry ; Liver Cirrhosis ; chemically induced ; drug therapy ; Malondialdehyde ; metabolism ; Oxidative Stress ; drug effects ; Plant Extracts ; pharmacology ; Rats ; Superoxide Dismutase ; metabolism ; Transforming Growth Factor beta1 ; metabolism ; gamma-Glutamyltransferase ; metabolism

OBJECTIVETo discuss the reverse effect of Yinchenhao decoction(YCHD) in dimethyl nitrosamine (DMN)-induced hepatic fibrosis in rats.

METHODThe rat hepatic fibrosis model was established through the intraperitoneal injection with 1% dimethyl nitrosamine (DMN) with a dose of 1.0 mL x kg(-1) x d(-1) for consecutively three weeks, once for the first three days of each. The rats were randomly divided into six groups: the silymarin positive control group (50.0 mg x kg(-1) x d(-1), YCHD high (20.0 g x kg(-1) d(-1)), middle (8.0 g x kg(-1) x d(-1)) and low (3.2 g x kg(-1) x d(-1)) dose groups, the model group and the normal control group. The model group and the normal control group were orally administered with normal saline for consecutively five weeks. The pathologic changes in liver tissues were observed by HE staining. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), g-glutamyltransferase (g-GGT), hyaluronic acid (HA), laminin (LN), collagen type IV (CIV) and type III procollagen amino terminal peptide (PIIINP) in serum were determined. The metabolite profiling of amino acid and the content of hydroxyproline in liver tissues were also measured.

RESULTCompared with the model group, YCHD high and middle dose groups could significantly reverse the pathologic changes in liver tissues of rats. YCHD could reduce the levels of ALT, AST, gamma-GGT, HA, LN, CIV, PIIINP in serum and the content of hydroxyproline in liver tissues in a dose-dependent manner, and altered the metabolite profiling of amino acid in rat liver tissues.

CONCLUSIONYCHD has the effect in reversing dimethyl nitrosamine induced hepatic fibrosis in rats.

Alanine Transaminase ; metabolism ; Animals ; Aspartate Aminotransferases ; metabolism ; Collagen Type IV ; metabolism ; Dimethylnitrosamine ; adverse effects ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Hydroxyproline ; metabolism ; Liver ; drug effects ; enzymology ; metabolism ; Liver Cirrhosis ; chemically induced ; drug therapy ; enzymology ; Male ; Rats ; Rats, Sprague-Dawley

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 investigate the effects of ancient Chinese medical formula Xiayuxue Decoction ([symbols; see text], XYXD) on activation of hepatic stellate cells (HSCs) and defenestration of sinusoidal endothelial cells (SECs) in CCl4-induced fibrotic liver of mice.

METHODSHigh performance liquid chromatography was used to identify the main components of XYXD and control the quality of extraction. C57BL/6 mice were induced liver fibrosis by CCl4 exposure and administered with XYXD for 6 weeks simultaneously. Liver tissue was investigated by hematoxylin-eosin and Sirius-red staining. Sinusoidal fenestrations were observed by scanning electronic microscopy and fluorescent immunohistochemistry of PECAM-1 (CD31). Whole liver lysates were detected of α-smooth muscle actin (α-SMA) and type-I collagen by Western blot. Primary rat HSCs-T6 cells were analyzed by detecting α-SMA, F-actin, DNA fragmentation through confocal microscopy, Western blot, terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay and cellomics arrayscan, respectively.

RESULTSAmygdalin and emodin in XYXD were identified. XYXD (993 mg/kg) inhibited Sirius red positive area up to 70.1% (P<0.01), as well as protein levels of α-SMA and type-I collagen by 42.0% and 18.5% (P<0.05) respectively. In vitro, XYXD (12.5 μg/mL, 50 μg/mL) suppressed the activation of HSCs and reversed the myofibroblastic HSCs into quiescent, demonstrated as inhibition of fluorescent F-actin by 32.3% and 46.6% (P<0.05). Besides, XYXD induced the apoptosis of HSC-T6 cells by 20.0% (P<0.05) and 49.5% (P<0.01), evidenced by enhanced TUNEL positivity. Moreover, ultrastructural observation suggested XYXD inhibited defenestration of SECs, which was confirmed by 31.1% reduction of protein level of CD31 (P<0.05).

CONCLUSIONSXYXD inhibited both HSCs activation and SECs defenestration which accompany chronic liver injuries. These data may help to understand the underlying mechanisms of XYXD for prevetion of chronic liver diseases.

Actins ; metabolism ; Animals ; Carbon Tetrachloride Poisoning ; drug therapy ; Collagen Type I ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Endothelium ; drug effects ; pathology ; Hepatic Stellate Cells ; drug effects ; pathology ; ultrastructure ; Liver Cirrhosis ; chemically induced ; drug therapy ; pathology ; Male ; Mice, Inbred C57BL ; Microscopy, Electron, Scanning ; Myofibroblasts ; drug effects ; pathology ; ultrastructure ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism ; Primary Cell Culture ; Rats, Sprague-Dawley

The aim of this study was to evaluate the anti-inflammatory and hepatoprotective effects of the total flavonoid C-glycosides isolated from Abrus mollis extracts (AME). In the anti-inflammatory tests, xylene-induced ear edema model in mice and carrageenan-induced paw edema model in rats were applied. The hepatoprotective effects of AME were evaluated with various in vivo models of acute and chronic liver injury, including carbon tetrachloride (CCl4)-induced hepatitis in mice, D-galactosamine (D-GalN)-induced hepatitis in rats, as well as CCl4-induced hepatic fibrosis in rats. In the acute inflammation experiment, AME significantly suppressed xylene-induced ear edema and carrageenan-induced paw edema, respectively. In the acute hepatitis tests, AME significantly attenuated the excessive release of ALT and AST induced by CCl4 and D-GalN. In CCl4-induced hepatic fibrosis model, AME alleviated liver injury induced by CCl4 shown by histopathological sections of livers and improved liver function as indicated by decreased liver index, serum ALT, AST, TBIL, and ALP levels and hydroxyproline contents in liver tissues, and increased serum ALB and GLU levels. These results indicated that AME possesses potent anti-inflammatory activity in acute inflammation models and hepatoprotective activity in both acute and chronic liver injury models. In conclusion, AME is a potential anti-inflammatory and hepatoprotective agent and a viable candidate for treating inflammation, hepatitis, and hepatic fibrosis.
Abrus ; chemistry ; Animals ; Anti-Inflammatory Agents ; pharmacology ; therapeutic use ; Biomarkers ; blood ; Carbon Tetrachloride ; Carrageenan ; Chemical and Drug Induced Liver Injury ; drug therapy ; metabolism ; pathology ; Edema ; chemically induced ; drug therapy ; Female ; Flavonoids ; pharmacology ; therapeutic use ; Galactosamine ; Glycosides ; pharmacology ; therapeutic use ; Inflammation ; chemically induced ; drug therapy ; pathology ; Liver ; drug effects ; metabolism ; pathology ; Liver Cirrhosis ; drug therapy ; Male ; Mice, Inbred ICR ; Monosaccharides ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Protective Agents ; pharmacology ; therapeutic use ; Rats, Sprague-Dawley ; Xylenes

Terlipressin is a vasopressin analogue that is widely used in the treatment of hepatorenal syndrome or variceal bleeding. Because it acts mainly on splanchnic vessels, terlipressin has a lower incidence of severe ischemic complications than does vasopressin. However, it can still lead to serious complications such as myocardial infarction, skin necrosis, or bowel ischemia. Herein we report a case of severe ischemic bowel necrosis in a 46-year-old cirrhotic patient treated with terlipressin. Although the patient received bowel resection, death occurred due to ongoing hypotension and metabolic acidosis. Attention should be paid to patients complaining of abdominal pain during treatment with terlipressin.
Bilirubin/blood ; Creatinine/blood ; Electrocardiography ; Fatal Outcome ; Hepatorenal Syndrome/*drug therapy ; Humans ; Intestinal Mucosa/pathology ; Intestines/surgery ; Liver Cirrhosis/diagnosis/therapy ; Lypressin/adverse effects/*analogs & derivatives/therapeutic use ; Male ; Middle Aged ; Necrosis/*chemically induced/surgery ; Tomography, X-Ray Computed ; Vasoconstrictor Agents/*adverse effects/*therapeutic use

OBJECTIVETo observe the effect and mechanism of isoorientin from Gypsophila elegans on alcohol-induced hepatic fibrosis in rats.

METHODninety healthy male Wistar rats were randomly divided into six groups: the normal control group, the model control group, the colchicines group (positive control, 1.0 mg x kg(-1) x d(-1)), the high, middle and low-dose isoorientin groups (20, 50, 100 mg x kg(-1) x d(-1)). The normal control group received normal saline, while other groups received alcohol to cause hepatic fibrosis. After 24-weeks treatment, the alanine aminotransferase (ALT), aspartate aminotransferase (AST), Interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), hyaluronic acid (HA), laminin (LN), type III precollagen (PCIII), hydroxyproline (Hyp), Myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were assayed according to the manufacturer's instructions, the alpha-SMA and TGF-beta1 were detected by western blotting, and the histopathological changes was observed by H&E staining.

RESULTIsoorientin could improve the liver function by decreasing the activity of ALT, AST, IL-6, TNF-alpha, MDA, MPO, HA, LN, PCIII and Hyp (P < 0.05), increasing the activity of SOD and GSH-Px (P < 0.05), and reducing the expression of alpha-SMA and TGF-beta1 (P < 0.05). In addition, the high and middle-dose isoorientin groups showed more remarkable effect

CONCLUSIONIsoorientin from G. elegans can protect hepatic fibrosis induced by alcohol.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Drugs, Chinese Herbal ; administration & dosage ; Ethanol ; adverse effects ; Glutathione Peroxidase ; blood ; Humans ; Liver Cirrhosis ; chemically induced ; drug therapy ; enzymology ; prevention & control ; Luteolin ; administration & dosage ; Male ; Protective Agents ; administration & dosage ; Rats ; Rats, Wistar ; Transforming Growth Factor beta1 ; metabolism