OBJECTIVETo investigate the role of adiponectin (ADP) and adiponectin receptor 2 (adipoR2) in pathology of fatty liver, and to investigate the effect of Chinese herbal decoction (Qushi Huayu Decoction, QHD) on fatty liver disease.

METHODSTwo experimental fatty liver models were used. One was induced with high-fat diet for ten weeks, and the rats were divided into normal, model and QHD group, the QHD group was administrated with QHD during the last four weeks. The other experimental fatty liver model was induced by subcutaneous injection of carbon tetrachloride (CCl4) in combination with high-fat and low-protein diet for four weeks, and the rats were also divided into normal, model and QHD group, the QHD group was administrated with QHD during the last two weeks. The observation items include: (1) hepatic steatosis (H.E. staining); (2) serum ADP, hepatic triglyceride (TG), free fatty acid (FFA) and adipoR2; (3) correlation among serum ADP content, hepatic TG, FFA and adipoR2.

RESULTS(1) Serious hepatic steatosis, increased hepatic TG and FFA, decreased serum ADP and hepatic adipoR2 were observed in the two models (P less than 0.01). QHD administration significantly reduced the hepatic TG and FFA, and increased serum ADP and hepatic adipoR2 (P less than 0.01) in these two models. (2) Inverse correlation was observed between hepatic TG, FFA and serum ADP, hepatic adipoR2 in these two models.

CONCLUSION(1) Decreased serum ADP and hepatic adipR2 may play important roles in pathological process of fatty liver. (2) QHD administration increased the serum ADP and hepatic adipoR2.

Adiponectin ; blood ; Animals ; Carbon Tetrachloride ; administration & dosage ; Dietary Fats ; administration & dosage ; Disease Models, Animal ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Fatty Acids, Nonesterified ; metabolism ; Fatty Liver ; drug therapy ; etiology ; metabolism ; pathology ; Liver ; drug effects ; metabolism ; pathology ; Male ; Phytotherapy ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Wistar ; Receptors, Adiponectin ; metabolism ; Triglycerides ; metabolism

AIM: The potential of Trifolium pratense (red clover) extract in the prevention of lipid disorder has attracted increasing attention in recent years. In this study, the aim was to determine whether and how red clover extract affected the development of murine diet-induced non-alcoholic steatohepatitis. METHODS: Non-alcoholic steatohepatitis was induced in C57BL/6 mice by feeding mice with a methionine-choline-deficient (MCD) diet. Hematoxylin and eosin staining was used for histological analyses. Real-time PCR was used to analyze the mRNA expression levels. RESULTS: Hepatic steatosis and necroinflammation was observed in MCD diet-fed mice, and this diet-induced steatosis was significantly attenuated, whereas liver inflammation was not significantly attenuated, by red clover extract treatment. Consistent with the results of H&E staining, the MCD diet-induced increase of liver triglycerides and cholesterol levels were significantly reduced by red clover extract treatment. However, with the improvement in hepatic steatosis, mRNA levels of acetyl CoA oxidase, carnitine palmitoyl transferase-1, and liver fatty acid-binding protein, three genes regulated by peroxisome proliferator-activated receptor (PPAR) α, were unaffected. CONCLUSION Red clover extract alleviated MCD diet-induced hepatic steatosis, but did not ameliorate liver inflammation in C57BL/6 mice, and the improvement in hepatic steatosis was not through activating PPARα.
Animals ; Cholesterol ; metabolism ; Choline Deficiency ; complications ; Diet ; adverse effects ; Disease Models, Animal ; Inflammation ; drug therapy ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Methionine ; deficiency ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease ; drug therapy ; etiology ; metabolism ; PPAR gamma ; metabolism ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; RNA, Messenger ; metabolism ; Trifolium ; Triglycerides ; metabolism

OBJECTIVEThe prevalence of non-alcoholic fatty liver disease (NAFLD) has markedly increased. Insulin resistance has been implicated in the pathogenesis of NAFLD. This study was aimed at observing the relationship between insulin resistance and NAFLD, and evaluating the role of pioglitazone (PGZ) acting as insulin-sensitizing agents in the prevention and treatment of rat fatty liver induced by high fat feeding.

METHODSThe rats were separated randomly into 6 groups: model group I were fed high fat diet for 8 weeks, PGZ prevention group were given PGZ 4 mg/(kg.d) simultaneously, while control group I were fed normal food for 8 weeks; model group II were fed high fat diet for 16 weeks, PGZ treatment group were given PGZ 4 mg/(kg.d) orally simultaneous with high fat diet for 8 weeks after high fat feeding for 8 weeks, control group II were fed normal food for 16 weeks. The rats were sacrificed after 8 weeks and 16 weeks respectively. Liver weight, body weight, serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), tumor necrosis factor alpha (TNF-alpha), fasting blood glucose (FBG), fasting plasma insulin (FINS), HOMA (homeostasis model assessment) insulin resistance index (HOMA-IR), and the liver histology of rats of all groups were assayed.

RESULTSAfter 8 weeks, the liver in model group I showed typical steatosis, accompanied with mild to moderate lobular inflammatory cell infiltration, liver indexes and serum levels of ALT, AST, ALP, TNF-alpha were significantly increased (P<0.05) compared with control group I. Whereas, the degree of hepatic injury was attenuated in PGZ prevention group, liver indexes and serum levels of ALT, ALP were significantly decreased (P<0.05) compared with model group I. After 16 weeks, notable steatosis, and lobular inflammation were observed in model group II rat liver, while the degree of hepatic injury was attenuated in the PGZ treatment group. Liver index, serum levels of ALT, AST, ALP, FINS and HOMA-IR were significantly increased (P<0.05) in model group II compared with control group II. Whereas, in PGZ treatment group, serum levels of AST and FINS showed decreasing tendency, liver indexes, serum levels of ALT, ALP, TNF-alpha and HOMA-IR were significantly decreased compared with model group II.

CONCLUSIONInsulin resistance plays a role in the pathogenesis of NAFLD in rats. Pioglitazone can attenuate insulin resistance and biochemical and histological injury in high fat-induced fatty liver in rats.

Alanine Transaminase ; blood ; Alkaline Phosphatase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Fatty Liver ; drug therapy ; etiology ; metabolism ; pathology ; Insulin Resistance ; Liver ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Thiazolidinediones ; therapeutic use ; Tumor Necrosis Factor-alpha ; analysis

Nonalcoholic steatohepatitis (NASH) is characterized by hepatocyte injury and inflammatory cell infiltration, which has been linked to peripheral insulin resistance and increased levels of triglycerides in the liver. The purposes of this study were to establish a mouse model of NASH by feeding mice a 60% high-fat diet (HFD) and to demonstrate the anti-fibrotic effects of oleuropein, which has been shown to have anti-oxidant and anti-inflammatory properties, in this HFD-induced mouse model of NASH. C57BL/6 mice were divided into three groups: a regular diet group (Chow), a HFD group and an oleuropein-supplemented HFD group (OSD), which was fed a 0.05% OSD for 6 months. The effects of oleuropein in this model were evaluated using biochemical, histological and molecular markers. The expression levels of alpha-smooth muscle actin (alpha-SMA)and collagen type I in the HFD and OSD groups were evaluated using real-time PCR and western blotting. The body weight, biochemical marker levels, nonalcoholic fatty liver disease activity score, homeostasis model of assessment-insulin resistance (HOMA-IR) and leptin levels observed in the HFD group at 9 and 12 months were higher than those observed in the Chow group. The HOMA-IR and leptin levels in the OSD group were decreased compared with the HFD group. In addition, alpha-SMA and collagen type I expression were decreased by oleuropein treatment. We established a NASH model induced by HFD and demonstrated that this model exhibits the histopathological features of NASH progressing to fibrosis. Our results suggest that oleuropein may be pharmacologically useful in preventing the progression of steatohepatitis and fibrosis and may be a promising agent for the treatment of NASH in humans.
Actins/genetics/metabolism ; Animals ; Antihypertensive Agents/*therapeutic use ; Collagen Type I/genetics/metabolism ; Diet, High-Fat/*adverse effects ; Fatty Liver/*drug therapy/etiology/metabolism ; Fibrosis/etiology/metabolism/prevention & control ; Iridoids/*therapeutic use ; Leptin/genetics/metabolism ; Liver/metabolism/pathology ; Mice ; Mice, Inbred C57BL

OBJECTIVETo observe the effects of Taizhi'an capsule in treatment of hyperlipidemic fatty liver.

METHODThe model rats were induced by feeding high caloric diet for 8 weeks, then fifty rats were randomly divided into five groups, and each group had ten rats, the Taizhi'an groups (high dose 1 000 mg x kg(-1), middle dose 500 mg x kg(-1), low dose 250 mg x kg(-1)), the Yishanfu group and the model group. Liver index (liver weight/body weight), liver function, blood lipid, liver lipid, the content of MDA and SOD in liver were assayed after therapy, and observe Pathologic changes in rats liver.

RESULTLiver index, blood lipid, liver lipid, liver function increased significantly (P < 0.001) in model rats, and the content of SOD in liver decreased significantly (P < 0.05), Liver histology expressed mild to moderate fat denaturation; After being treated with high and middle dose of Taizhi'an capsule for six weeks, blood lipid, liver function decreased significantly (P < 0.001), and liver lipid decreased significantly (P < 0.001, P <0.05), the content of SOD in liver increased significantly (P < 0.05), meanwhile liver histology was closed to normal.

CONCLUSIONTaizhian capsule is effective in the treatment of hyperlipidemic induced fatty liver.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Capsules ; Cholesterol ; blood ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Fatty Liver ; drug therapy ; etiology ; metabolism ; Hyperlipidemias ; complications ; Ligustrum ; chemistry ; Liver ; drug effects ; metabolism ; pathology ; Male ; Malondialdehyde ; metabolism ; Phytotherapy ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; Triglycerides ; blood ; metabolism ; Triterpenes ; administration & dosage ; pharmacology

OBJECTIVETo investigate whether total saponins of Panax notoginseng (tPNS) can ameliorate oxidative stress and insulin resistance (IR) in the high fat induced nonalcoholic fatty liver disease (NAFLD) rat model and to explore the relationship between oxidative stress and IR.

METHODSTotally 50 healthy rats were randomly divided into the normal control group (NC), the model group, the high dose tPNS group (at the daily dose of 160 mg/kg), the low dose tPNS group (at the daily dose of 80 mg/kg), and the bicyclol group (at the daily dose of 100 mg/kg), 10 in each group. Rats in the NC group were fed with standard forage. Those in the rest group were fed with high fat forage. Distilled water was given by gastrogavage to those in the NC group and the model group. Corresponding medication was performed for 4 weeks. Four weeks later Lee's index and body weight were measured. All rats were sacrificed to detect the wet weight of livers. Their sera was isolated and detected to calculate liver functions (serum ALT and AST levels). Levels of fasting blood glucose (FBG) and fasting insulin (FINS) were detected. Insulin sensitive index (ISI) and insulin resistance index (IRI) were calculated. Serum levels of TNF-alpha and malondialdehyde (MDA), contents of total superoxide dismutase (T-SOD), hydroxy radical level (-OH), and total antioxidant capacity (T-AOC) were measured. Pathological changes of livers was observed by HE staining of paraffin section.

RESULTSCompared with the NC group, rats' wet liver weight and Lee's index increased in the model group (P < 0.05), and results of light microscopy showed that obvious fatty degeneration occurred in livers. Compared with the model group, rats' wet liver weight and Lee's index, as well as ALT and AST could be obviously improved by tPNS and bicyclol (P < 0.05, P < 0.01). The fatty deposition of liver cells could also be alleviated. Compared with the NC group, serum levels of-OH, MDA, and TNF-alpha significantly increased, and activities of T-SOD and T-AOC decreased in the model group (P < 0.01), also accompanied with IR. Compared with the model group, concentrations of -OH, MDA, and TNF-alpha decreased after treated by tPNS (P < 0.05, P < 0.01), activities of T-SOD and T-AOC got recovered (P < 0.05, P < 0.01), and IR got obvious improvement (P < 0.01).

CONCLUSIONThe anti-oxidative stress effect and IR improving effect of tPNS might play partial roles in treating NAFLD.

Animals ; Diet, High-Fat ; Fatty Liver ; drug therapy ; etiology ; metabolism ; Ginsenosides ; pharmacology ; therapeutic use ; Insulin Resistance ; Male ; Oxidative Stress ; Panax notoginseng ; chemistry ; Rats ; Rats, Sprague-Dawley ; Saponins ; pharmacology ; therapeutic use