OBJECTIVETo study the effect of total flavonoids of Astmgali Radix (TFA) on liver cirrhosis induced with dimethylnitrosamine (DMN) in rats, and the effect on peroxisome proliferator-activated receptor γ (PPARγ), uncoupling protein 2 (UCP2) and farnesoid X receptor (FXR).

METHODSFifty-three Sprague-Dawley rats were randomly divided into a control group (10 rats) and a DMN group (43 rats). Rats in the DMN group were given DMN for 4 weeks and divided randomly into a model group (14 rats), a low-dosage TFA group (14 rats) and a high-dosage TFA group (15 rats) in the 3rd week. Rats were given TFA for 4 weeks at the dosage of 15 and 30 mg/kg in the low- and high-TFA groups, respectively. At the end of the experiment blood and liver samples were collected. Serum liver function and liver tissue hydroxyproline content were determined. hematoxylin-eosin (HE), Sirus red and immunohistochemical stainings of collagen I, smooth muscle actin (α-SMA) was conducted in paraffinembedded liver tissue slices. Real time polymerase chain reaction (PCR) was adopted to determine PPARγ, UCP2 and FXR mRNA levels. Western blot was adopted to determine protein levels of collagen I, α-SMA, PPARγ, UCP2 and FXR.

RESULTSCompared with the model group, TFA increased the ratio of liver/body weight (low-TFA group P<0.05, high-TFA group P<0.01), improved liver biochemical indices (P<0.01 for ALT, AST, GGT in both groups, P<0.05 for albumin and TBil in the high-TFA group) and reduced liver tissue hydroxproline content (P<0.01 in both groups) in treatment groups significantly. HE staining showed that TFA alleviated liver pathological changes markedly and Sirus red staining showed that TFA reduced collagen deposition, alleviated formation and extent of liver pseudolobule. Collagen I and α-SMA immunohistochemical staining showed that staining area and extent markedly decreased in TFA groups compared with the model group. TFA could increase PPARγ, it regulated target UCP2, and FXR levels significantly compared with the model group (in the low-TFA group all P<0.05, in the high group all P<0.01).

CONCLUSIONTFA could improve liver function, alleviate liver pathological changes, and reduce collagen deposition and formation of liver pseudolobule in rats with liver cirrhosis. The antifibrotic effect of TFA was through regulating PPARγ signal pathway and the interaction with FXR.

Actins ; metabolism ; Animals ; Blotting, Western ; Body Weight ; drug effects ; Collagen Type I ; metabolism ; Dimethylnitrosamine ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Flavonoids ; pharmacology ; therapeutic use ; Hydroxyproline ; metabolism ; Liver ; drug effects ; pathology ; Liver Cirrhosis ; blood ; drug therapy ; genetics ; pathology ; Male ; Organ Size ; drug effects ; PPAR gamma ; genetics ; metabolism ; Plant Extracts ; pharmacology ; therapeutic use ; RNA, Messenger ; genetics ; metabolism ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Receptors, Cytoplasmic and Nuclear ; genetics ; metabolism ; Uncoupling Protein 2 ; genetics ; metabolism

The purpose of the present study is to explore the effect of aliskiren on the proliferation of cardiac fibroblasts (CFs) in AGT-REN double transgenic hypertensive (dTH) mice. The cultured CFs from AGT-REN dTH mice were divided into AGT-REN group (dTH) and aliskiren group (ALIS). Cultured CFs from C57B6 mice were served as control (WT). The effect of different concentration of aliskiren (1 × 10, 1 × 10, 1 × 10, 1 × 10mol/L) on CFs proliferation was determined by MTT assay. After treatment with 1 × 10mol/L aliskiren for 24 h, α-SMA, collagen I, III and NADPH oxidase (NOX) protein expression in CFs of AGT-REN dTH mice were detected by Western blot. The collagen synthesis in CFs was assessed by hydroxyproline kit. The expression of ROS was determined by DHE. Results showed that the blood pressure and plasma Ang II levels were significantly increased and CFs proliferation was significantly increased as well in AGT-REN dTH mice compared with WT group. However, aliskiren intervention decreased CFs proliferation, myofibroblast transformation, as well as the collagen I and III synthesis in CFs of AGT-REN dTH mice. Meanwhile, aliskiren inhibited ROS content and NOX2/NOX4 protein expression in CFs of AGT-REN dTH mice. These results suggest that aliskiren decreases the cell proliferation, myofibroblast transformation and collagen production in CFs of AGT-REN dTH mice, which might be through inhibition of oxidative stress response.
Amides ; Animals ; Blood Pressure ; Cell Proliferation ; Cells, Cultured ; Collagen ; Collagen Type I ; Fumarates ; Heart ; Hydroxyproline ; Hypertension ; Mice ; Mice, Transgenic ; Myocardium ; Myofibroblasts ; NADPH Oxidases

OBJECTIVETo study the effect of Wu-He Dipsacus asper (WHDA), Traditional Chinese Medicine, injection on mice-aging model induced by D-galactose.

METHODSForty-eight Kunming mice (24 male and 24 female) were randomly divided into control group, model group, positive control group, 7.2 g/kg WHDA group, 3.6 g/kg WHDA group and 1.8 g/kg WHDA group with eight in each group. The model was induced through injecting D-galactose into peritoneal cavity and Morris water maze was used to detect the learning and cognitive ability of mice. The skin hydroxyproline, brain tissue malondialdehyde (MDA), lipofuscin (LP), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels of mice were detected; the IL-2 and IL-6 levels in serum of mice were detected by using double antibody sandwich ELISA method.

RESULTSEach WHDA group was significantly reduced in latency period compared with the model group during Morris water maze test (P < 0.05) and the number of mice in model group through the platform was less than other mice in each group (P < 0.05). The levels of MAD and LP of the control group and each WHDA group were less than model group in the detection of heart, brain tissue oxidation index (SOD, MAD, LP and GSH-Px, P < 0.05). The activity of SOD and GSH-Px in the control group and each WHDA group was significantly higher than that in the model group (P < 0.05). The skin hydroxyproline content of mice which had been injected with D-galactose was significantly lower than that in the control group (P < 0.05) and the skin hydroxyproline content of mice of WHDA group was significantly higher than that in the model group (P < 0.05). The IL-2, IL-6 levels in serum of mice in WHDA group were significantly higher than those in the control group and the model group (P < 0.05) and the IL-2, IL-6 levels in serum of mice in the model group were lower than those in the control group (P < 0.05).

CONCLUSIONThe effective constituents of WHDA have a variety of biological activity which can have a good effect on anti-aging by different ways, improving learning and memory function, eliminating free radicals antioxidant, and enhancing the body immunity and other aspects.

Aging ; drug effects ; physiology ; Animals ; Brain ; drug effects ; metabolism ; Dipsacaceae ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Female ; Galactose ; toxicity ; Glutathione Peroxidase ; metabolism ; Hydroxyproline ; metabolism ; Interleukins ; blood ; Learning ; drug effects ; Lipofuscin ; metabolism ; Male ; Malondialdehyde ; metabolism ; Memory ; drug effects ; Mice ; Skin ; drug effects ; metabolism ; Superoxide Dismutase ; metabolism

OBJECTIVETo observe the pharmacological effect of Cordyceps polysaccharide on dimethylnitrosamine (DMN)-induced liver fibrosis in rats.

METHODDMN rat liver fibrosis model was established and divided into the normal group (N, n = 6), the model group (M, n = 11), the Cordyceps polysaccharide group (C, n = 8) and the colchicine group (Q, n = 9). During the modeling for four weeks, Cordyceps polysaccharide (60 mg x kg(-1)) and colchicine (0.1 mg x kg(-1)) were orally administered for three weeks, while the model and normal groups were given disinfected water of the same amount.

OBSERVATIONserum ALT, AST, GGT and Alb, TBil content; content of hydroxyproline (Hyp) in liver tissues; liver pathology and collagen staining; SOD activity and MDA, GSH, GSH-Px in liver tissues; protein expression of proliferating cell nuclear antigen (PCNA) in liver tissues.

RESULTSerum ALT, AST, GGT, TBil significantly increased, and A1b decreased significantly in the model group. Hepatic Hyp significantly increased in the model group, whereas the index remarkably decreased in the Cordyceps polysaccharide group and the colchicine group. HE staining: the structure of normal hepatic lobules was damaged, with hepatocytes tumefaction and proliferation of connective tissues in portal tracts in the model group, while the Cordyceps polysaccharide group and the colchicine group recorded notable reduction in above pathological changes. Collagen staining: the model group showed hepatic lobule fibrous septum and many intact pseudolobules; while the Cordyceps polysaccharide group and the colchicine group witnessed decrease in collagen deposition. The model group showed significant decrease in SOD, GSH-Px and GSH and increase in MDA, whereas the Cordyceps polysaccharide group and the colchicine group recorded notable growth in GSH and GSH-Px. The model group showed significant decrease in protein expression of PCNA in liver tissues, while the Cordyceps polysaccharide group and the colchicine group showed significant reduction.

CONCLUSIONCordyceps polysaccharide can significantly inhibit DMN-induced liver fibrosis and lipid peroxidation in rats.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blotting, Western ; Collagen ; metabolism ; Cordyceps ; chemistry ; Dimethylnitrosamine ; toxicity ; Drug Administration Schedule ; Glutathione ; metabolism ; Glutathione Peroxidase ; Hydroxyproline ; Immunohistochemistry ; Lipid Peroxidation ; drug effects ; Liver ; drug effects ; metabolism ; pathology ; Liver Cirrhosis, Experimental ; blood ; etiology ; prevention & control ; Male ; Malondialdehyde ; metabolism ; Phytotherapy ; Polysaccharides ; administration & dosage ; pharmacology ; Proliferating Cell Nuclear Antigen ; metabolism ; Rats ; Rats, Wistar ; Superoxide Dismutase ; metabolism ; gamma-Glutamyltransferase ; blood

OBJECTIVETo observe the metabolic, regulatory and anti-oxidative effects of modified Bushen Huoxue Decoction (BSHXD), a Chinese herbal medicine for kidney (Shen)-reinforcement and blood-activation, on an osteoarthritis (OA) rabbit model.

METHODSA rabbit model for knee joint OA was established by the classic Hulth's method. The OA model rabbits were randomized into 5 groups: the model control group, the positive control group treated with glucosamine sulfate, and the three BSHXD treated groups treated respectively with low, moderate, and high doses of BSHXD. In addition, a normal control group and a sham-operated group were set up. Experimental animals were sacrificed after a 7-week treatment, and pathological changes in cartilaginous tissue were estimated using the Mankin criteria. Hydroxyproline (Hyp) and malonaldehyde (MDA) contents in blood serum and urine, as well as superoxide dismutase (SOD) activity and nitric oxide (NO) content in blood serum and knee joint synovial homogenates were detected.

RESULTSMankin scoring showed insignificant statistical differences between the various treatment groups (P >0.05), but all were better than the model control group (P <0.05). Serum and urinary contents of Hyp and MDA as well as serum and synovial levels of NO were significantly lower, but the SOD activity in blood serum and synovial tissue was higher in the BSHXD treated groups than in the model group P <0.01); the effect of BSHXD was dose-dependent to some extent.

CONCLUSIONThe modified BSHXD shows an effect of improving cartilage metabolism in experimental rabbits with OA, and possesses osteo-chondric protective effects in antagonizing peroxidation injury.

Animals ; Antioxidants ; pharmacology ; therapeutic use ; Cartilage, Articular ; drug effects ; pathology ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hydroxyproline ; blood ; urine ; Male ; Malondialdehyde ; metabolism ; Nitric Oxide ; blood ; Osteoarthritis ; blood ; drug therapy ; metabolism ; pathology ; Rabbits ; Superoxide Dismutase ; blood ; Synovial Membrane ; drug effects ; enzymology ; pathology

OBJECTIVETo investigate the effect of ursolic acid (UA) on the alloxan-induced myocardial fibrosis in mice and discuss the possible mechanism.

METHODSDiabetes was produced by a single injection of alloxan (70 mg/kg, i.v.) in mice. The mice were randomly divided into four groups: normal control group, model group, ursolic acid group (UA, 35 mg/kg, p.o.) and benazepril group (5 mg/kg, p. o.), and continuous administrated for 8 weeks. The blood glucose was measured 24 hours after the last administration. Detected the specific biochemical of myocardial tissue: superoxide dismutase (SOD), malondialdehyde (MDA) and hydroxyproline(HYP). Using masson staining to observe the morphology of the myocardial tissue. Immunohistochemistry was employed to determine the protein levels of TGF-beta1.

RESULTSCompared to normal group, the blood glucose, heart index, myocardial tissue MDA, HYP level were increased, and SOD activities were decreased in the diabetic mice, Masson stain showed that myocardial cells disarranged, myocardial collagen fibrosis hyperplasia. Meanwhile, the protein expression of TGF-beta1 was increased in model group. The UA group improved all the above significantly.

CONCLUSIONUA improves the myocardial collagen fibrosis in diabetic mice induced by alloxan, its mechanism may be related to inhibiting the expression of TGF-beta1 and antioxidation.

Animals ; Blood Glucose ; Collagen ; metabolism ; Diabetes Mellitus, Experimental ; metabolism ; pathology ; Fibrosis ; Hydroxyproline ; metabolism ; Male ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred Strains ; Myocardium ; metabolism ; pathology ; Oxidative Stress ; Superoxide Dismutase ; metabolism ; Transforming Growth Factor beta1 ; metabolism ; Triterpenes ; pharmacology

OBJECTIVETo study the effects of iptakalim (Ipt), an ATP-sensitive potassium channel opener, on cardiac remodeling induced by isoproterenol (ISO) in Wistar rats.

METHODSISO was given subcutaneously (85 mg/(kg x d), sc, 7 days) to induce cardiac remodeling in rats. The rats in Ipt treated group were administrated with Ipt 3 mg/kg (po) after ISO injection. After treated with Ipt for 6 weeks, the hemodynamic parameters were tested by an eight channel physiological recorder (RM-6000). Then the heart weight was weighed and the cardiac remodeling index was calculated. HE stain and Masson's stain were employed to perform histological analysis, the hydroxyproline(Hyp) content in cardiac tissue was detected by colorimetric method, radioimmunoassay was used to measure the plasma levels of endothelin-1 (ET-1) and prostacyclin (PGI2).

RESULTSSix weeks after ISO injection, the cardiac functions of model group were damaged markedly compared with those of normal group. The characteristics of ventricular remodeling in model group included that the heart weight index, myocyte cross-sectional area, myocardial fibrosis, and the hydroxyproline content in cardiac tissue were all increased significantly. The plasma level of ET-1 was increased, while the plasma level of PGI2 was decreased significantly. These changes could be reversed by Ipt treatment (3 mg/(kg x d) for 6 weeks).

CONCLUSIONIpt can reverse cardiac remodeling induced by isoproterenol in rats. The endothelial protective effect regulating effects of Ipt on the balance between the ET-1 and PGI2 system may be involved in its mechanisms.

Animals ; Endothelin-1 ; blood ; Hemodynamics ; Hydroxyproline ; metabolism ; Isoproterenol ; pharmacology ; KATP Channels ; drug effects ; Male ; Myocardium ; metabolism ; Propylamines ; pharmacology ; Prostaglandins I ; blood ; Rats ; Rats, Wistar ; Ventricular Remodeling ; drug effects

OBJECTIVETo investigate the effects of Corbrin Shugan capsule on dimethylnitrosamine (DMN)-induced hepatic fibrosis in rats.

METHODSHepatic fibrosis was induced by DMN in AD rats. The serum concentrations of III pro-collagen (III PC),laminin (LN) and tissue inhibitor of metalloproteinase-1(TIMP-1) were determined with ELISA. The concentration of albumin (ALB) in sera and the content of hydroxyproline (Hyp) in liver tissues were determined with chemical colorimetric and HPLC, respectively. The fibrosis area was measured with Motic Med 6.0 digital medical image analysis system.

RESULTSCompared to model group the high-dose (450 mg kg(-1)),mid-dose (270 mg kg(-1)) and low-dose (90 mg kg(-1)) groups of Corbrin Shugan capsule had significantly lower serum content of III PC [34.46 ± 13.95),(36.15 ± 9.46), and (40.58 ± 7.72)ng ml(-1) compared with (49.38 ± 10.95)ng ml(-1),P<0.05 or P<0.01],TIMP-1 [(16.65 ± 4.24),(16.66 ± 4.34),and (18.99 ± 6.05)ng ml(-1) compared with (30.84 ± 14.48)ng ml(-1), P<0.05 or P<0.01], LN [(12.94 ± 4.29), (12.96 ± 3.21),and (15.32 ± 8.00)ng ml(-1) compared with (30.22 ± 17.00)ng ml(-1),P<0.05 or P<0.01] and smaller hepatic fibrosis area [(0.02240 ± 0.01337), (0.02176 ± 0.01460) and (0.02384 ± 0.01405)μm(2) compared with vs (0.03929 ± 0.01732)μm2, P<0.05 or P<0.01]; the high-dose and mid-dose groups of Corbrin Shugan capsule had significantly lower content of Hyp in liver tissues [(0.77 ± 0.09) and (0.81 ± 0.09)μg μmg(-1) compared with (1.06 ± 0.33)μg mg(-1),P<0.05 or P<0.01]; and the high-dose group of Corbrin Shugan capsule significantly increased the content of ALB in sera [(34.02 ± 4.17)g L(-1) compared with (30.25 ± 4.21)g L(-1),P<0.05].

CONCLUSIONCorbrin Shugan capsule is effective in treatment of DMN-induced hepatic fibrosis in rats.

Albumins ; metabolism ; Animals ; Capsules ; Collagen Type III ; blood ; Dimethylnitrosamine ; adverse effects ; Drugs, Chinese Herbal ; therapeutic use ; Hydroxyproline ; metabolism ; Laminin ; blood ; Liver Cirrhosis, Experimental ; drug therapy ; Male ; Rats ; Rats, Sprague-Dawley ; Tissue Inhibitor of Metalloproteinase-1 ; blood

OBJECTIVETo observe the effect of traditional Chinese medicine formulas clearing away heat and promoting blood circulation-Biejiayinzi (BJYZ), Gexiazhuyu Tang (GXZYT) and Fugan Wan (FGW) on liver fibrosis in CCl4 mice by screening and analyzing formula-syndrome database of kidney and liver fibrosis based on the principle of formula-syndrome, compared with pivot-harmonizing decoction.

METHODTen-week-old male C57BL/6 mice, with the weight of (20 +/- 3) g, were randomly divided into 6 groups: the normal group, the model group, the BJYZ group, the GXZY group, the FGW group and the XST group. Except the normal group, other groups were abdominally injected with 10% CCl4 olive oil solution a dose of 2 mL x kg(-1) body weight for four weeks, three times each week. Meanwhile, the latter four groups were administered with extracts of BJYZ, GXZYT, FGW and XST, respectively, once every day, concomitantly continued CCl4 administration. The normal and the model groups were given the same volume of deionized water. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (gamma-GT), Alb and TBil were detected by chemiluminescence. The hydroxyproline (HYP) content was detected by acid hydrolysis method. The hepatic collagen deposition was evaluated with Sirius red staining.

RESULTCompared with the normal group, the model group recorded notable decrease in weight and increase in the ratio of liver weight and body weight and the ratio of spleen weight and body weight, with obvious fatty degeneration and inflammatory necrosis in liver cells. Collagen fiber deposition was so notable to form fibrous septums and pseudolobules. The levels of serum ALT, AST, TBil, gamma-GT, the HYP content in liver tissue and the deposition of hepatic collagen were significantly increased in the model group. Compared with model group, Serum AST were significantly decreased in BJYZ group as gamma-GT decreased in the GXZYT group, without notable decrease in degeneration and inflammatory necrosis in liver cells and collagen deposition. The GXZYT group showed significant decrease in gamma-GT, with slight improvement in degeneration and inflammatory necrosis in liver cells and reduction in collagen deposition. The ratio of liver weight and body weight, AST, gamma-GT and HYP content were significantly decreased in the FGW group, with slight improvement in degeneration and inflammatory necrosis in liver cells and reduction in collagen deposition. The XST group showed decrease in the ratio of liver weight and body weight, with no obvious change in inflammation and fibrosis of hepatic tissue.

CONCLUSIONFGW shows the best effect of prevention and treatment of liver fibrosis in CCl4 mice.

Animals ; Blood Circulation ; drug effects ; Body Temperature ; drug effects ; Carbon Tetrachloride ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hydroxyproline ; metabolism ; Liver ; drug effects ; metabolism ; pathology ; Liver Cirrhosis ; drug therapy ; metabolism ; pathology ; prevention & control ; Male ; Mice ; Mice, Inbred C57BL ; Organ Size ; drug effects

OBJECTIVETo investigate the therapeutic effect of Corbrin shugan capsule for treatment of alcoholic hepatic fibrosis in rats.

METHODSThe rat model of alcoholic hepatic fibrosis was induced by intragastric administration of alcohol repeatedly. The serum procollagen III (PC III), laminin (LN) and tissue inhibitors of metalloproteinase-1 (TIMP-1) levels were measured with ELISA, and the content of hydroxyproline (Hyp) in liver tissue were determined with colorimetric method. Collagen deposition in liver tissue was observed with Masson's staining, and the fibrosis area was measured with digital medical image analysis system (Motic Med 6.0).

RESULTSCompared with the model control group, the serum TIMP-1 and LN levels and hepatic fibrosis area in liver tissue significantly decreased in Corbrin shugan capsule groups with doses of 0.09,0.27 and 0.45 g*kg(-1), and the serum PC III and the Hyp contents in liver tissue also decreased of Corbrin shugan capsule groups with doses of 0.27 and 0.45g*kg(-1).

CONCLUSIONCorbrin shugan capsule can decrease serum PC III, TIMP-1 and LN levels and Hyp levels in liver tissue and hepatic fibrosis area in rats, indicating it may have therapeutic effect on alcoholic hepatic fibrosis.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Hydroxyproline ; metabolism ; Laminin ; blood ; Liver ; metabolism ; pathology ; Liver Cirrhosis, Alcoholic ; drug therapy ; metabolism ; pathology ; Male ; Procollagen ; blood ; Rats ; Tissue Inhibitor of Metalloproteinase-1 ; blood