The saponins in different parts of Gynostemma pentaphyllum were analyzed via UPLC-Q-TOF-MS~E. A total of 46 saponins were identified, and the underground part had 26 saponins more than the aboveground part, most of which were trisaccharide saponins. The rat model of hyperlipidemia was established with high-fat diet. This study explored the lipid-lowering activity of total saponins in the underground part of G. pentaphyllum, so as to provide a theoretical basis for the comprehensive utilization of the underground part of G. pentaphyllum. A total of 99 healthy SD rats were randomly assigned into a blank group, a model group, a positive drug group, an aboveground total saponins group, and low-, medium-, and high-dose underground total saponins groups. Except the blank group, the other groups were fed with high-fat diet for 6 weeks. Then, the blood was collected from the orbital cavity to determine whether the modeling was successful according to the serum levels of total cholesterol(TC) and triglyceride(TG). After intragastric administration of the corresponding agents for 30 continuous days, the physical state of the rats were observed, and the body weight and liver specific gravity were measured. Furthermore, the levels of TC, TG, low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), alanine transaminase(ALT), aspartate transaminase(AST), bilirubin, and total bile acids in serum, as well as the levels of superoxide dismutase(SOD), malondialdehyde(MDA), peroxidase proliferator-activated receptor(PPAR-γ) in the liver tissue, were determined. The pathological changes of liver was observed via HE staining. The results showed that the aboveground total saponins and medium-and high-dose underground total saponins can treat hepatocyte steatosis, lower TC, TG, LDL-C, ALT, AST, total bilirubin, MDA, and PPAR-γ levels, and increase HDL-C and SOD levels in the model rats. The effect tended to be more obvious with the increase in dosage. Therefore, the total saponins in the underground part of G. pentaphyllum have good pharmacological effect of reducing blood lipid, which provides a theoretical basis for the comprehensive utilization of the underground part of G. pentaphyllum.
Alanine Transaminase/analysis* ; Animals ; Aspartate Aminotransferases/analysis* ; Bile Acids and Salts/blood* ; Bilirubin/blood* ; Cholesterol, LDL/blood* ; Diet, High-Fat/adverse effects* ; Gynostemma/chemistry* ; Hypolipidemic Agents/therapeutic use* ; Lipoproteins, HDL/blood* ; Liver/metabolism* ; Malondialdehyde/analysis* ; Peroxisome Proliferator-Activated Receptors/analysis* ; Rats ; Rats, Sprague-Dawley ; Saponins/therapeutic use* ; Superoxide Dismutase ; Triglycerides/blood* ; Trisaccharides/therapeutic use*

PURPOSE: Liver metabolism plays a pivotal role in the development of metabolic disorders. We aimed to investigate the clinical and laboratory risk factors associated with alanine aminotransferase (ALT) levels in young adolescents from an urban population in Korea. METHODS: A population of 120 apparently healthy adolescents aged 12–13 years was included in the cross-sectional design study; 58 were overweight or obese and 62 were of normal weight. We estimated anthropometric and laboratory measurements, including waist-to-height ratio, blood pressure, insulin sensitivity, aspartate aminotransferases (AST), ALT, and lipid profiles. RESULTS: The mean ages of the overweight or obese and normal weight participants were 12.9±0.3 and 13.0±0.3 years, respectively. Height, weight, body mass index, waist circumference, waist-to-height ratio, systolic and diastolic blood pressure, AST, ALT, total cholesterol, low-density lipoprotein-cholesterol, triglyceride, insulin, and the homeostatic model assessment of insulin resistance (HOMA-IR) score were significantly higher and the high-density lipoprotein-cholesterol and quantitative insulin-sensitivity check index were significantly lower in the overweight/obese participants in comparison to the normal-weight participants (all P < 0.05). In multivariate linear regression analysis, waist-to-height ratio, systolic blood pressure, and HOMA-IR score were independently and positively associated with serum ALT levels. CONCLUSION: Screening for ALT levels in adolescents may help to differentiate those at risk of metabolic abnormalities and thus prevent disease progression at an early age.
Adolescent ; Alanine Transaminase ; Alanine ; Aspartate Aminotransferases ; Blood Pressure ; Body Weight ; Cholesterol ; Disease Progression ; Humans ; Insulin ; Insulin Resistance ; Korea ; Linear Models ; Liver ; Mass Screening ; Metabolism ; Obesity ; Overweight ; Risk Factors ; Triglycerides ; Urban Population ; Waist Circumference

To study the mechanism and action of Cinnamomi Ramulus in ameliorating intrahepatic cholestasis induced by α-isothiocyanate( ANIT) in rats by regulating FXR pathway. Forty SD rats were randomly divided into normal group,model group,positive control( ursodeoxycholic acid) group( 60 mg·kg~(-1)),Cinnamomi Ramulus treatment( 60 mg·kg~(-1)·d~(-1)) group,and Cinnamomi Ramulus treatment( 20 mg·kg~(-1)·d~(-1)) group,with 8 rats in each group. Except for the normal control group,the other groups were intragastrically administered with the corresponding concentrations of continuous aqueous solution( 0. 005 m L·g~(-1)),once a day,for 7 days.Except for the normal group,the other groups were treated with ANIT( 100 mg·kg~(-1)),once a day,for 3 days. Blood was taken from the abdominal aorta 24 hours after the last administration,and serum alanine aminotransferase( ALT),aspartate aminotransferase( AST),total bilirubin( TBi L),and total bile acid( TBA) were measured. 1. 5-2 cm of rat liver tissue was taken. After fixation with10% formaldehyde,paraffin-embedded sections were taken,HE staining was performed,and immunohistochemistry( IHC) was used to analyze the expression of FXR. RNA and protein were extracted from rat liver tissue to detect FXR mRNA expression,as well as bile acid synthesis and detoxification,transport related SHP,UGT2 B4,BSEP protein expressions at downstream of FXR. Compared with the normal group,serum ALT,AST,TBi L,and TBA levels were elevated in the model group( P<0. 01),liver damage was severe,FXR protein's optical density decreased,FXR mRNA expression decreased,and SHP,UGT2 B4,BSEP protein expressions were decreased( P<0. 05,P<0. 01). Compared with the model group,the drug group could reduce serum ALT,AST,TB,TBA levels to different degrees( P<0. 05,P<0. 01),alleviate liver tissue damage,increase the optical density of FXR protein,and promote the expressions of FXR mRNA and FXR,SHP,BSEP and UGT2 B4 proteins( P<0. 05,P<0. 01). Cinnamomi Ramulus can alleviate ANIT-induced intrahepatic cholestasis,and reduce hepatocyte injury and serum ALT,AST,TBi L and TBA levels. The mechanism may be through FXR-SHP,FXR-UGT2 B4,FXR-BSEP signaling pathways. Therefore,in the pathogenesis of intrahepatic cholestasis,we can try to further explore in alleviating intrahepatic cholestasis with Cinnamomi Ramulus,so as to provide effective drugs for clinical treatment of intrahepatic cholestasis.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Bile Acids and Salts ; blood ; Bilirubin ; blood ; Cholestasis, Intrahepatic ; chemically induced ; drug therapy ; Cinnamomum ; chemistry ; Isothiocyanates ; Liver ; Plant Extracts ; pharmacology ; RNA-Binding Proteins ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley

This study was to investigate the mechanism of safflower yellow injection for regulating inflammatory response against myocardial ischemia-reperfusion injury( MIRI) in rats. Male Wistar rats were randomly divided into sham operation group,model group,Hebeishuang group,safflower yellow injection high,medium and low dose groups. MIRI model was established by ligating left anterior descending coronary artery. Myocardial histopathological changes were observed by HE staining; myocardial infarct size was detected by TTC staining; content and changes of tumor necrosis factor-α( TNF-α) and interleukin-6( IL-6),serum creatine kinase( CK),aspartate aminotransferase( AST),and lactate dehydrogenase( LDH) were detected by biochemical method or enzyme-linked immunosorbent assay( ELISA). Western blot assay was used to detect the protein expression of Toll-like receptor 4( TLR4) and nuclear factor-κB( NF-κB p65) in myocardial tissues. The results showed that as compared with the sham operation group,the myocardial arrangement of the model group was disordered,with severe edemain the interstitial,significantly increased area of myocardial infarction,increased activities of AST,CK and LDH in serum,and significantly increased contents of TNF-α and IL-6; the expression levels of TLR4 and NF-κB( p65) protein in myocardial tissues were also increased. As compared with the model group,the myocardial tissues were arranged neatlyin the Hebeishuang group and safflower yellow injection high,medium and low dose groups; the edema was significantly reduced; the myocardial infarct size was significantly reduced; the serum AST,CK,LDH activity and TNF-α,IL-6 levels were significantly decreased,and the expression levels of TLR4 and NF-κB( p65) protein in myocardial tissues were decreased. As compared with the Hebeishuang group,the myocardial infarct size was larger in the safflower yellow injection high,medium and low dose groups; the activities of AST,CK and LDH in serum and the contents of TNF-α and IL-6 in serum were higher,but there was no statistically significant difference in the expression levels of TLR4 and NF-κB( p65) protein in tissues. It is suggested that safflower yellow injection has a significant anti-MIRI effect,and its mechanism may be related to the regulation of TLR-NF-κB pathway to inhibit inflammatory response.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Aspartate Aminotransferases ; blood ; Chalcone ; analogs & derivatives ; pharmacology ; Creatine Kinase ; blood ; Interleukin-6 ; metabolism ; L-Lactate Dehydrogenase ; blood ; Male ; Myocardial Reperfusion Injury ; drug therapy ; Rats ; Rats, Wistar ; Toll-Like Receptor 4 ; metabolism ; Transcription Factor RelA ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

Antrodia camphorata, a well-known and highly valued edible medicinal mushroom with intriguing activities like liver protection, has been traditionally used for the treatment of alcoholic liver disease. A. camphorata shows highly medicinal and commercial values with the demand far exceeds the available supply. Thus, the petri-dish cultured A. camphorata (PDCA) is expected to develope as a substitute. In this paper, nineteen triterpenes were isolated from PDCA, and thirteen of them were the unique anthroic acids in A. camphorata, including the main content antcin K, which suggested that PDCA produced a large array of the same anthroic acids as the wild one. Furthermore, no obvious acute toxicity was found suggesting the edible safety of PDCA. In mice alcohol-induced liver injury model, triglyceride (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) had been reduced by the PDCA powder as well as the main content antcin K, which indicated that the PDCA could protect alcoholic liver injury in mice model and antcin K could be the effective component responsible for the hepatoprotective activities of PDCA against alcoholic liver diseases.
Alanine Transaminase ; blood ; Aldehyde Dehydrogenase ; blood ; Animals ; Antrodia ; chemistry ; Aspartate Aminotransferases ; blood ; Biological Products ; chemistry ; pharmacology ; therapeutic use ; Chemical and Drug Induced Liver Injury ; etiology ; prevention & control ; Cholestenes ; chemistry ; pharmacology ; therapeutic use ; Cholesterol, VLDL ; blood ; Disease Models, Animal ; Ethanol ; toxicity ; Female ; Fruiting Bodies, Fungal ; chemistry ; Liver ; drug effects ; metabolism ; pathology ; Liver Diseases, Alcoholic ; prevention & control ; Male ; Malondialdehyde ; blood ; Mice ; Molecular Structure ; Triglycerides ; blood ; Triterpenes ; chemistry ; pharmacology ; therapeutic use

Cardiovascular disease (CVD) is the most common cause of death in patients with non-alcoholic fatty liver disease (NAFLD). New therapeutic strategies which have the potential for slowing down the evolution of NAFLD and reducing CVD-related mortality are urgently needed. Statins are well recognized in the treatment of dyslipidemia, but their use in the treatment of NAFLD is limited due to the safety concerns. Ilexgenin A (IA) is one of the main bioactive compounds in 'Shan-lv-cha', an herbal tea commonly used in China. In the present study, we investigated the possible synergistic therapeutic effects of IA and simvastatin (SV) on NAFLD. IA or SV showed beneficial effects on the rats with NAFLD by lowering the liver weight, liver index and plasma levels of alanine aminotransferase and aspartate aminotransferase, regulating abnormal metabolism of lipids and ameliorating steatosis in liver. IA significantly enhanced the hypolipidemic and anti-inflammation effects of SV. Furthermore, a sensitive, accurate, convenient and reproducible LC-MS method was developed to investigate the effects of IA on the pharmacokinetics of SV. No significant changes were observed in pharmacokinetic parameters of SV and simvastatin hydroxy acid in the IA plus SV co-treated group in comparison with those in the group treated with SV alone. The mRNA levels and activity of CYP3A1 were not altered by IA. In conclusion, the results obtained from the present study should be helpful for further clinical application of SV and IA alone or in combination.
Alanine Transaminase ; metabolism ; Animals ; Aspartate Aminotransferases ; metabolism ; Cytochrome P-450 CYP3A ; genetics ; metabolism ; Diet, High-Fat ; Disease Models, Animal ; Drug Synergism ; Drug Therapy, Combination ; Lipids ; blood ; Liver ; metabolism ; pathology ; physiopathology ; Male ; Molecular Structure ; Non-alcoholic Fatty Liver Disease ; blood ; drug therapy ; Rats ; Rats, Sprague-Dawley ; Simvastatin ; analogs & derivatives ; pharmacokinetics ; therapeutic use ; Transcription, Genetic ; Triterpenes ; chemistry ; therapeutic use

Nonalcoholic fatty liver disease (NAFLD) and type 2 Diabetes Mellitus (T2DM) are highly prevalent diseases and are closely associated, with NAFLD being present in the majority of T2DM patients. In Asian traditional medicine, Mori Cortex is widely used for the treatment of diabetes and hyperlipidemia. However, whether it has a therapeutic effect on T2DM associated with NAFLD is still unknown. The present study showed that the oral treatment with Mori Cortex extract (MCE; 10 g·kg·d) lowered the blood lipid levels and reversed insulin resistance (IR) in high fat-diet/streptozotocin-induced type 2 diabetes in rats. The expression levels of sterol receptor element-binding protein-1c (SREBP-1c) and carbohydrate-responsive element binding protein (ChREBP), which are involved in steatosis in NAFLD rats, were measured in the liver samples. MCE decreased the protein and mRNA expression levels of SREBP-1c and ChREBP. In conclusion, down-regulation of SREBP-1c and ChREBP might contribute to the protective effect of MCE on hepatic injury and IR in the rats with T2DM associated with NAFLD.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; genetics ; Diabetes Mellitus, Type 2 ; blood ; chemically induced ; drug therapy ; metabolism ; Diet, High-Fat ; adverse effects ; Disease Models, Animal ; Down-Regulation ; drug effects ; Insulin ; blood ; Insulin Resistance ; physiology ; Lipid Metabolism ; drug effects ; genetics ; Liver ; drug effects ; physiopathology ; Male ; Morus ; Non-alcoholic Fatty Liver Disease ; blood ; chemically induced ; drug therapy ; metabolism ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Streptozocin

Tanreqing (TRQ), a traditional Chinese medicine (TCM) formula, can alleviate liver injury and improve liver function. Its pharmacological mechanisms of actions are still unclear due to its complex components and multi-target natures. Metabolomic study is an effective approach to investigating drug pharmacological actions, new diagnostic markers, and potential mechanisms of actions. In the present study, a new strategy was used to evaluate the protective effect of TRQ capsule against carbon tetrachloride (CCl)-induced hepatotoxicity in rats, by analyzing metabolic profiling of endogenous bile acids (BAs) along with biochemical and histological analyses. BAs concentrations were determined by ultra-performance liquid chromatography coupled with quadrupole mass spectrometry (UPLC-MS). Principal component analysis and partial least squares discriminant analysis were then employed to analyze the UPLC-MS results and compare the hepatoprotective effect of TRQ capsule in different groups at the doses of 0.36, 1.44, and 2.88 g·kg body weight, respectively. Moreover, our results suggested that taurocholic acid (TCA) and taurohyodesoxycholic acid (THDCA) were the most important biochemical markers, which were indicative of CCl-induced acute hepatic damage and hepatoprotective effect of TRQ capsule. Therefore, this new strategy would be an excellent alternative method for evaluating hepatoprotective effect and proposing potential mechanisms of action for other drugs as well.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Bile Acids and Salts ; blood ; metabolism ; Biomarkers ; blood ; Carbon Tetrachloride ; pharmacology ; Chemical and Drug Induced Liver Injury ; drug therapy ; metabolism ; pathology ; Chromatography, Liquid ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Female ; Liver ; drug effects ; pathology ; Male ; Mass Spectrometry ; Metabolome ; drug effects ; Metabolomics ; Rats ; Rats, Wistar ; Taurocholic Acid ; blood ; Taurodeoxycholic Acid ; analogs & derivatives ; blood

To explore the protective effect of rosiglitazone (RGZ) on hepatic ischemia reperfusion injury (HIRI) and the underlying mechanisms.
 Methods: A rat model of ischemia-reperfusion injury was established by clamping the left and middle lobe of liver with noninvasive vascular clamp. A total of 30 Sprague-Dawley rats were randomly divided into a sham group, an HIRI group, and a RGZ group (10 rats in each group). Two hours after reperfusion, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, lactate dehydrogenase (LDH) level, malondialdehyde (MDA) content and catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were examined. HE staining was used to observe liver pathological morphology. The liver peroxisome proliferators-activated receptor γ (PPAR-γ), p-PPAR-γ, nuclear factor related factor 2 (Nrf-2), antioxidant response element (ARE), heme oxygenase 1 (HO-1) and quinone oxidoreductase-1 (NQO-1) were detected by Western blot.
 Results: Compared with the HIRI group, the levels of ALT, AST, LDH and MDA in the RGZ group were significantly decreased (all P<0.05), while the levels of Nrf-2, ARE, HO-1 and NQO-1 in the RGZ group were significantly increased. The hepatic swelling, necrosis and pathological damage were decreased (all P<0.05). In addition, there was no difference in the level of PPAR-γ between the 2 groups (P>0.05).
 Conclusion: PPAR-γ agonist RGZ can attenuate HIRI, which may be related to activating Nrf2/ARE signaling pathway and enhancement of antioxidant ability.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Catalase ; blood ; Disease Models, Animal ; Glutathione Peroxidase ; blood ; L-Lactate Dehydrogenase ; blood ; Ligation ; Liver ; blood supply ; metabolism ; Malondialdehyde ; blood ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; blood ; etiology ; prevention & control ; Rosiglitazone ; Superoxide Dismutase ; blood ; Thiazolidinediones ; therapeutic use

OBJECTIVES: To study the effects of ursolic acid on liver injury in diabetic mice induced by high-fat diet combined with streptozotocin(STZ), and to explore its possible mechanisms. METHODS: Diabetes mellitus was induced in twenty male ICR mice by a combination of high-fat diet for 6 weeks with low-dose streptozotocin (30 mg/kg, i. p.) for 5 consecutive days. After 9 days, fasting blood glucose levels were determined. Mice with fasting blood glucose levels exceeded 11. 1 mmol/L were diagnosed as diabetic mice and selected for further experiment. These mice were randomly divided into two groups(each group of 10):diabetic group, ursolic acid group (100 mg/kg, i. g.), and another 10 mice were set as control group. After continuous administration for 8 weeks, body weight (BW) were weighed, fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate transaminase (AST) in serum and superoxide dismutase (SOD), malondialdehyde (MDA) in liver were measured. HE staining was used to observe pathological changes of liver tissue. RESULTS: Compared with the control group, the level of FBG, TC, TG, ALT, AST, MDA were dramatically increased (<0. 05, <0. 01) and SOD was markedly decreased (<0.01) in the diabetic group; HE staining showed that parts of liver cells swelled and had a light fatty degeneration as well as lymphocyte infiltrated around the portal area in model group. Compared with the diabetic group, the level of FBG, TC, TG, ALT, AST, MDA were significantly declined (<0.05, <0.01) and SOD was considerably increased (<0.01) in the ursolic acid group; HE staining showed that the liver cells relatively arranged in order, edema was not obvious and inflammatory cells infiltrated lightly in the ursolic acid group. CONCLUSIONS Ursolic acid has a protective effect on liver injury in diabetic mice induced by high-fat diet combined with STZ by intraperitoneal ingector, and its mechanism may be associated with lowering blood glucose, regulating the lipid metabolism, reducing oxidative stress and enhancing the ability of anti-oxidation in liver.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blood Glucose ; Cholesterol ; blood ; Diabetes Mellitus, Experimental ; physiopathology ; Diet, High-Fat ; Fatty Liver ; drug therapy ; Liver ; metabolism ; physiopathology ; Male ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred ICR ; Random Allocation ; Superoxide Dismutase ; metabolism ; Triglycerides ; blood ; Triterpenes ; pharmacology