A targeted metabolomics study was conducted on the bile acid profiles in the liver and feces of rats induced by a high-fat diet and intervened by ginsenoside Rb_1, along with the detection of FXR pathway gene expression in the liver, to explore and clarify its mechanism of action. The content of biochemical indicators in the serum were detected using an automatic biochemical analyzer. Hematoxylin and eosin(HE) staining and oil red O staining were used to detect pathological changes and lipid deposition in the liver. RT-PCR was used to detect the mRNA expression of FXR, small heterodimer partner(SHP), cholesterol 7 alpha-hydroxylase(CYP7A1), and sterol regulatory element-binding protein-1c(SREBP-1c) in the liver. Targeted bile acid metabolomics technology was employed to analyze changes in bile acid profiles in liver tissue and feces, and a correlation analysis was performed between key genes such as FXR, SHP, CYP7A1, SREBP-1c and differential bile acid metabolites. The results showed that ginsenoside Rb_1 significantly reduced the levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), and high-density lipoprotein cholesterol(HDL-C) in the serum, alleviated the large fat vacuoles and lipid deposition in the liver, increased the expression of FXR mRNA in the liver, and decreased the expression of SREBP-1c mRNA. The expression of CYP7A1 and SHP mRNA was increased, but the differences were not statistically significant. Targeted bile acid metabolomics showed that ginsenoside Rb_1 could restore the levels of 9 bile acids in the liver and 8 bile acids in the feces. Ginsenoside Rb_1 also increased the percentage of taurocholic acid(TCA) in the liver(56.78%) and the percentage of 12-ketolithocholic acid(12-KLCA) in the feces(26.10%). Pathway enrichment analysis revealed two pathways involved in bile acid metabolism: primary bile acid biosynthesis and taurine and hypotaurine metabolism. Correlation analysis showed that FXR, SHP, CYP7A1, and SREBP-1c were positively correlated with multiple differential bile acids. These results suggest that ginsenoside Rb_1 may intervene in lipid metabolism disorders induced by a high-fat diet by regulating the FXR pathway and modulating bile acid profiles in the liver and feces.
Animals ; Bile Acids and Salts/metabolism* ; Rats ; Ginsenosides/pharmacology* ; Male ; Receptors, Cytoplasmic and Nuclear/genetics* ; Liver/drug effects* ; Diet, High-Fat/adverse effects* ; Metabolomics ; Rats, Sprague-Dawley ; Feces/chemistry* ; Cholesterol 7-alpha-Hydroxylase/metabolism* ; Sterol Regulatory Element Binding Protein 1/genetics* ; Humans

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

OBJECTIVETo investigate the effects of hydro-alcoholic extract of Launaea acanthodes, a blood glucose lowering plant in folk medicine of Iran, on the structure of seminiferous tubules and serum gonadotropin and testosterone levels in hyperglycemic rats.

METHODSTwenty-four Wistar rats were randomly allocated into 4 groups (n=6): control, streptozotocin (STZ), STZ + insulin [STZ + Ins, 5 IU/(kg•day)], and STZ + Launaea acanthodes extract [STZ + Ext, 150 mg/(kg•day)]. Blood samples were collected at the 2nd and 4th weeks for detection of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) with enzyme-linked immuno sorbent assay (ELISA), and the right testes of rats were removed at the 7th week for the evaluation of diameter and wall thickness of seminiferous tubules and number of Leydig cells using unbiased stereological techniques.

RESULTSIn comparison with the control group, at the 2nd week FSH (0.45 vs 0.03, 0.02, 0.02 IU/L in STZ, STZ + Ins and STZ + Ext groups, respectively) and LH (1.02 vs 0.37, 0.2, 0.29 IU/L) showed significant decreases (all P<0.05) and testosterone (4.2 vs 8.37, 7.78, 11.8 ng/mL) showed a remarkable increase (all P<0.05). The levels of these hormones became closer in the STZ + Ext and the STZ + Ins groups to the control at the 4th week. A significant decrease in diameter and wall thickness of seminiferous tubules and number of Leydig cells were observed in the STZ group as compared with the control (P<0.01).

CONCLUSIONSAdministration of Launaea extract demonstrated a beneficial impact on the protection of testis from pathogenic and degenerative effects of hyperglycemia which may be partly due to its potential antioxidative effects.

Animals ; Asteraceae ; chemistry ; Blood Glucose ; metabolism ; Cell Count ; Cholesterol ; blood ; Ethanol ; chemistry ; Gonadotropins ; blood ; Hyperglycemia ; blood ; drug therapy ; pathology ; Insulin ; blood ; Leydig Cells ; drug effects ; pathology ; Lipoproteins ; blood ; Male ; Plant Extracts ; pharmacology ; therapeutic use ; Rats, Wistar ; Seminiferous Tubules ; drug effects ; pathology ; Testosterone ; blood ; Triglycerides ; blood ; Water ; chemistry

OBJECTIVETo comparatively study the effects of Rhubarbs from different regions on blood lipid and antioxi dation of hyperlipidemia rats.

METHODSMale rats were randomly divided into 9 groups ( n = 8) and fed with high-fat diet to replicate the hyperlipidemia model. Meanwhile, Rheum tanguticum was administrated intragastrically at two doses (3.0 g/kg and 1.0 g/kg), once a day for continuous 28 days. The effects of Rheum tanguticum planted in Gannan (RT-GN), Rheum tanguticum planted in Xinin (RT-XN) and Rheum plmatum planted in Lixian (RP-LX) were evaluated through detecting the parameters of blood lipids, blood viscosity and antioxidant system.

RESULTST-GN, RT-XN and RP-LX in the range of 1.0-3.0 g/kg could decrease the blood levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and malonaldehyde (MDA) in blood. Besides, they could reduce blood viscosity, increase high density lipoprotein (HDL) level and upregulate the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Interestingly, their effects on blood viscosity was obviously in a dose dependent manner. In addition, the effects of RT-GN on LDL, MDA and blood viscosity were not significantly different from those of RT-XN and better than those of RP-LX.

CONCLUSIONThe RT has better hypolipidemic effects than the RP, but RT-GN and RT-XN are not different from the above effects.

Animals ; Antioxidants ; metabolism ; Blood Viscosity ; Cholesterol ; blood ; Diet, High-Fat ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Glutathione Peroxidase ; metabolism ; Hyperlipidemias ; drug therapy ; Lipids ; blood ; Lipoproteins, HDL ; blood ; Lipoproteins, LDL ; blood ; Male ; Malondialdehyde ; blood ; Rats ; Rheum ; chemistry ; Superoxide Dismutase ; metabolism ; Triglycerides ; blood

OBJECTIVETo investigate the effect of Antrodia cinnamomea on gene expression related to aortal endothelial injury of rats with hyperlipidemia.

METHODFifty SD rats were randomly divided into five groups: the normal control group (NG), the model group (MG), the antrodia cinnamomea groups of low, middle and high doses (AC-LG, AC-MG, AC-HG, 250, 500, 1 000 mg x kg(-1)). The rats were fed with high-fat diets to establish the hyperlipidemia model. After the drug administration for 10 weeks, their serum lipid, SOD, MDA and ox-LDL, LOX-1, P38 MAPK and NF-kappaB mRNA and protein expression were respectively determined, and the aortal endothelial injury was observed under electron microscope.

RESULTIn the model group, the contents of TC, TG and LDL-C significant increased (P < 0.01), whereas the content of HDL-C significant decreased (P < 0.01). Compared with the model group, both the AC-M group and the AC-H group showed reduction in endothelial injury and significant decrease in the content of TC, TG and LDL-C (P < 0.05 or P < 0.01). The content of HDL-C increased, but with no significant difference. SOD activity in serum remarkably increased (P < 0.05 or P < 0.01), MDA and ox-LDL levels dramatically decreased (P < 0.05 or P < 0.01).

CONCLUSIONA. cinnamomea can alleviate endothelial lipid injury by inhibiting the expressions of LOX-1, P38MAPK and NF-kappaB in aorta and better protect aortal endothelial cells from oxidative lipid injury.

Animals ; Antrodia ; chemistry ; Aorta ; drug effects ; metabolism ; ultrastructure ; Atherosclerosis ; blood ; genetics ; prevention & control ; Biological Products ; pharmacology ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Endothelium, Vascular ; drug effects ; metabolism ; pathology ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; drug effects ; Hyperlipidemias ; blood ; genetics ; prevention & control ; Lipoproteins, LDL ; blood ; Male ; Malondialdehyde ; blood ; Microscopy, Electron ; NF-kappa B ; blood ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Scavenger Receptors, Class E ; blood ; genetics ; metabolism ; Superoxide Dismutase ; blood ; Triglycerides ; blood ; p38 Mitogen-Activated Protein Kinases ; blood ; genetics ; metabolism

Pineapple (Ananas comosus) leaves contain mainly phenolic components with antioxidant and hypolipidemic effects. One of the principle components is p-coumaric acid. In this study, the transport behavior of p-coumaric acid, was observed after the administration of pineapple leaf phenols in vitro. Simultaneously, the effect of the phenols on glucose, total cholesterol and triglycerides transportation and metabolism in HepG2 cells was also observed. The results showed that the phenols had good transport characteristics. 5 min after the administration, p-coumaric acid of the phenols could be detected, and the content of p-coumaric acid reached the peak concentration after 60 min of the administration. p-coumaric acid of phenols have time-and dose-dependent manner. While promoting glucose transporter (GLUT4) and low density lipoprotein receptor (LDLR) expression, the phenols decreased intracellular lipid content. This reduction of intracellular lipid content was highly correlated with the promotion of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) expression, while the reduction of intracellular glucose levels was correlated with glycogen synthesis in the cells.
Ananas ; chemistry ; Biological Transport ; drug effects ; Cholesterol ; metabolism ; Glucose ; metabolism ; Hep G2 Cells ; Humans ; Lipid Metabolism ; drug effects ; Plant Extracts ; pharmacology ; Plant Leaves ; chemistry

The authors designed to separate, purify and determine the monosaccharide composition of the polysaccharide from Cordyceps militaris, and study its effect on reverse cholesterol transport in vivo by isotope tracing assay. Polysaccharides were separate and purify by ion exchange column Q-sepharose Fast Flow and size exclusion column Sephacryl S200HR; the molecular weight and monosaccharide composition of the polysaccharides were determined by high performance gel permeation chromatography and high performance liquid chromatography coming with pre-column derivation, respectively. Finally, three purified polysaccharides CMBW1, CMBW2 and CMYW1 were obtained, their total carbohydrate contents were 87%, 89%, 95%, respectively; their protein contents were 6.5%, 1.3%, 2.8%, respectively; their molecular weights were 772.1, 20.9, 13.2 kDa, respectively; CMBW1 was composed of mannose, glucosamine, rhamnose, glucuronic acid, glucose, galactose and arabinose with a molar ratio of 7.25: 0.17: 1.29: 0.23: 6.30: 11.08: 0.79; CMBW2 was composed of mannose, glucosamine, galactose and arabinose with a molar ratio of 2.40: 0.16: 2.92: 0.24; CMYW1 was composed of mannose, glucosamine, glucuronic acid and glucose with a molar ratio of 0.59: 0.57: 0.45: 25.61. Polysaccharide at 50 mg x kg(-1) could significantly improve the transport of 3H- cholesterol to blood and excretion from feces. All of the three purified polysaccharides CMBW1, CMBW2 and CMYW1 were heteropolysaccharide; and they could improve reverse cholesterol transport in vivo, the underlying mechanisms are being studied.
Animals ; Biological Transport ; drug effects ; Cholesterol ; metabolism ; Chromatography, High Pressure Liquid ; instrumentation ; methods ; Cordyceps ; chemistry ; Mice ; Monosaccharides ; analysis ; isolation & purification ; Polysaccharides ; chemistry ; isolation & purification ; pharmacology ; Tritium

The effects of magnolol (Mag) on hyperglycemia and hyperlipemia, hepatic oxidative stress and cytochrome P4502E1 (CYP2E1) activity of diabetic rats induced by high-fat diet (HFD) and streptozotocin (STZ) were studied. After oral administration of Mag (25, 50 and 100 mg x kg(-1) x d(-1)) for continuous 10 weeks, the blood glucose and lipids (TC, TG and LDL-C) levels, as well as the hepatic CYP2E1 activity and MDA content of diabetic rats, decreased significantly (P < 0.05 or P < 0.01), whereas the oral glucose tolerance and hepatic antioxidant enzymatic activities (CAT and GSH-Px) of diabetic rats, increased significantly (P < 0.05 or P < 0.01). The results indicated that Mag was effective against the hepatic oxidative damage, hyperglycemia and hyperlipemia of diabetic rats induced by HFD and STZ, and the inhibition of Mag on hepatic CYP2E1 activity could be an important mechanism of Mag against hepatic insulin resistance and oxidative damage.
Animals ; Biphenyl Compounds ; isolation & purification ; pharmacology ; Blood Glucose ; metabolism ; Cholesterol ; blood ; Cholesterol, LDL ; blood ; Cytochrome P-450 CYP2E1 ; metabolism ; Diabetes Mellitus, Experimental ; blood ; drug therapy ; metabolism ; Diet, High-Fat ; Glucose Tolerance Test ; Hypoglycemic Agents ; isolation & purification ; pharmacology ; Lignans ; isolation & purification ; pharmacology ; Liver ; metabolism ; Magnolia ; chemistry ; Male ; Oxidative Stress ; drug effects ; Plants, Medicinal ; chemistry ; Protective Agents ; pharmacology ; Rats ; Rats, Wistar ; Streptozocin ; Triglycerides ; blood

Abrus mollis is a widely used traditional Chinese medicine for treating acute and chronic hepatitis, steatosis, and fibrosis. It was found that the total flavonoid C-glycosides from Abrus mollis extract (AME) showed potent antioxidant, anti-inflammatory, and hepatoprotective activities. To further investigate the hepatoprotective effect of AME and its possible mechanisms, lipopolysaccharide (LPS)-induced liver injury models were applied in the current study. The results indicated that AME significantly attenuated LPS-induced lipid accumulation in mouse primary hepatocytes as measured by triglyceride (TG) and total cholesterol (TC) assays and Oil Red O staining. Meanwhile, AME exerted a protective effect on LPS-induced liver injury as shown by decreased liver index, serum aminotransferase levels, and hepatic lipid accumulation. Real-time PCR and immunoblot data suggested that AME reversed the LPS-mediated lipid metabolism gene expression, such as sterol regulatory element-binding protein-1 (SREBP-1), fatty acid synthase (FAS), and acetyl-CoA carboxylase 1 (ACC1). In addition, LPS-induced overexpression of activating transcription factor 4 (ATF4), X-box-binding protein-1 (XBP-1), and C/EBP homologous protein (CHOP) were dramatically reversed by AME. Furthermore, AME also decreased the expression of LPS-enhanced interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2). Here, it is demonstrated for the first time that AME ameliorated LPS-induced hepatic lipid accumulation and that this effect of AME can be attributed to its modulation of hepatic de novo fatty acid synthesis. This study also suggested that the hepatoprotective effect of AME may be related to its down-regulation of unfolded protein response (UPR) activation.
Abrus ; chemistry ; Animals ; Anti-Inflammatory Agents ; pharmacology ; therapeutic use ; Antioxidants ; pharmacology ; therapeutic use ; Chemical and Drug Induced Liver Injury ; drug therapy ; metabolism ; Cholesterol ; metabolism ; Down-Regulation ; Flavonoids ; pharmacology ; therapeutic use ; Glycosides ; pharmacology ; therapeutic use ; Hepatocytes ; drug effects ; metabolism ; Inflammation Mediators ; metabolism ; Lipid Metabolism ; drug effects ; Lipopolysaccharides ; Liver ; cytology ; drug effects ; metabolism ; Male ; Mice, Inbred Strains ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Transaminases ; blood ; Triglycerides ; metabolism ; Unfolded Protein Response ; drug effects

Brain ; Cholesterol ; chemistry ; Cytoskeleton ; drug effects ; Endothelial Cells ; cytology ; metabolism ; Hemolysin Proteins ; chemistry ; pharmacology ; Humans ; Phalloidine ; pharmacology ; Pseudopodia ; drug effects ; Stress Fibers ; drug effects ; rac1 GTP-Binding Protein ; metabolism ; rhoA GTP-Binding Protein ; metabolism