Structural characterization and hypolipidemic effect of Cyclocarya paliurus polysaccharide in rat.

Polysaccharide is one of the important active ingredients of Cyclocarya paliurus (Batal.) Iljinskaja leaves. The aims of this work were to analyze the structure of the polysaccharide of Cyclocarya paliurus (Batal.) Iljinskaja leaves (CPP), and to investigate the antihyperlipidemic effect of CPP on high-fat emulsion (HFE)-induced hyperlipidaemic rats. CPP, comprised of two polysaccharides with average molecular weight (Mw) of 1.35×10(5)Da and 9.34×10(3)Da, was consisted of rhamnose, arabinose, xylose, mannose, glucose and galactose in the molar ratio of 1.00:2.23:0.64:0.49:0.63:4.16. Oral administration of CPP could significantly decrease levels of serum total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), increase high density lipoprotein (HDL-C) in hyperlipidemic rats. CPP exerts therapeutic effects on hyperlipidaemic rats, by up-regulating expressions of adipose triglyceride lipase (ATGL) and peroxisome proliferator-activated receptor alpha (PPARα), via down-regulating fatty acid synthase (FAS) and hydroxy methylglutaryl coenzyme A reductase (HMG-CoA). This study demonstrates that CPP may be beneficial for the treatment of hyperlipidemia.

Yang ZW ，Ouyang KH ，Zhao J ，Chen H ，Xiong L ，Wang WJ ... -  《-》

Cholesterol-lowering effects and potential mechanisms of different polar extracts from Cyclocarya paliurus leave in hyperlipidemic mice.

Cyclocarya paliurus Batal., native only to China, is widely consumed as a Chinese traditional folk medicine for the prevention and treatment of hyperlipidemia, obesity, and diabetes. The aim of the study is to investigate the cholesterol-lowering effect and potential mechanisms of different polar extracts from Cyclocarya paliurus leaves in mice fed with high-fat-diet. Cyclocarya paliurus leaves extracts were orally administered to diet-induced hyperlipidemic mice for 4 weeks. Simvastatin was used as a positive control. Body weight, food intake, histopathology of liver and adipose tissues, hepatic and renal function indices, lipid profiles in the serum and liver were evaluated. Total bile acid concentrations of the liver and feces were also measured. Furthermore, the activities and mRNA expression of cholesterol metabolism-related enzymes including 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, cholesterol 7α-hydroxylase (CYP7A1) and acyl-CoA cholesterol acyltransferase 2 (ACAT2) in the livers of the mice were analyzed. LC-MS detection was performed to identify the components in the active fraction of Cyclocarya paliurus extracts. Different Cyclocarya paliurus polar extracts, especially ChE reduced the levels of serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and hepatic TC and TG, enhanced the level of serum high-density lipoprotein cholesterol (HDL-C), restored hepatic and renal function indices and histomorphology. HMG-CoA reductase activity and mRNA expression were decreased, while CYP7A1 activity and mRNA expression as well as the level of fecal and hepatic bile acid were increased by ChE. LC-MS analysis of ChE revealed the presence of six main triterpenoids, which might be responsible for its antihyperlipidemic bioactivity. Evidently ChE possesses the best antihyperlipidemic activity, and the cholesterol-lowering effect is at least partly attributed to its role in promoting the conversion of cholesterol into bile acids by upgrading the activity and mRNA expression of CYP7A1 and inhibiting those of HMG-CoA reductase to lower the cholesterol biosynthesis.

Jiang C ，Wang Q ，Wei Y ，Yao N ，Wu Z ，Ma Y ，Lin Z ，Zhao M ，Che C ，Yao X ，Zhang J ，Yin Z ... -  《-》

Antihyperlipidemic effect of Cyclocarya paliurus (Batal.) Iljinskaja extract and inhibition of apolipoprotein B48 overproduction in hyperlipidemic mice.

Cyclocarya paliurus (CP) Batal., the sole species in its genus, is a native plant to China. As a traditional Chinese folk medicine, the tree leaves have been widely used for the treatment of metabolic disorders, including hyperlipidemia, obesity, diabetes and hypertension. The study aimed to evaluate the antihyperlipidemic effect of CP ethanol extract, as well as its inhibitory activity on apolipoproteinB48 (apoB48), in normal and hyperlipidemic mice. The antihyperlipidemic effect of CP was evaluated in hyperlipidemic mice induced by high-fat diet for 4 weeks. CP ethanol extract (0.37, 0.75 and 1.5g/kg/day) was orally administrated once daily. Lipids and antioxidant profiles, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), together with the indices of hepatic and renal functions were examined. RT-qPCR and western blotting were used to analysis the expression levels of tumor necrosis factor (TNF-α), total- and triglyceride-rich apoB48 (TRL-apoB48), as well as the phosphorylation of the mitogen-activatein kinase (MAPK). CP as well as simvastatin remarkably lowered the levels of TC, TG, LDL-C and MDA, and at the same time, elevated the HDL-C, SOD and GSH-Px in high-fat diet mice. It also decreased the serum concentration of total- and TRL-apoB48 in the fasting state. CP inhibited TNF-α expression and phosphorylation level of MAPK. Furthermore, the HE staining of liver and kidney, together with hepatic and renal function analysis showed hepato- and renoprotective activities of CP. These results suggested that CP possesses beneficial potentials for use in treating hyperlipidemia and the underlying lipid-lowering mechanism might associate with a down-regulation of the intestinal-associated lipoprotein apoB48, which may provide evidence about its practical application for treating hyperlipidemia and its complications.

Ma Y ，Jiang C ，Yao N ，Li Y ，Wang Q ，Fang S ，Shang X ，Zhao M ，Che C ，Ni Y ，Zhang J ，Yin Z ... -  《-》

Antihyperlipidemic and hepatoprotective activities of polysaccharide fraction from Cyclocarya paliurus in high-fat emulsion-induced hyperlipidaemic mice.

The objective of this study was to analyse the structure of CPP-2, and to observe the pharmacological effects of CPP-2 on lipid metabolism and oxidative stress. CPP-2, eluted as two main fractions comprised of two polysaccharides with Mw of 307 and 3.7kDa, was mainly consisted of rhamnose, mannose, glucose and galactose in a molar ratio of 1.00:0.78:3.22:0.45. The results showed that treatment with CPP-2 could improve blood lipid levels (TC, TG, HDL-C and LDL-C), liver lipid levels (TC and TG) and antioxidant status (SOD, T-AOC, GSH-PX, MDA and LPO). In addition, the histopathological observations of mice livers and the GPT activities indicated that CPP-2 could attenuate liver cell injury. The present findings demonstrated that CPP-2 might be effective in lowering lipid and protecting against HFE-induced hyperlipidemia and non-alcoholic fatty liver.

Yang Z ，Wang J ，Li J ，Xiong L ，Chen H ，Liu X ，Wang N ，Ouyang K ，Wang W ... -  《-》

Genome-wide DNA methylation profiling of high-fat emulsion-induced hyperlipidemia mice intervened by a polysaccharide from Cyclocarya paliurus (Batal) Iljinskaja.

Genome-wide DNA methylation was used to study the lipid-lowering effect of Cyclocarya paliurus (Batal) Iljinskaja polysaccharide (CPP). The objective of this study was to investigate the hypolipidemic effects and the potential underlying mechanisms of action of CPP-2 in high-fat emulsion (HFE)-induced mice. The results showed that CPP-2 reduced the level of genome-wide DNA methylation in the liver of HFE-induced mice, which had a lipid-lowering effect by regulating the AMP-activated protein kinase (AMPK) signaling-, fatty acid metabolism-, fatty acid biosynthesis- and adipocytokine signaling pathways. A series of lipid metabolism genes were screened out by conjoint analysis of the Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Hereafter, fatty acid synthase (FAS) and peroxisome proliferators-activated receptor α (PPARα) as target genes were selected to validate the accuracy of the results. The findings demonstrated that CPP-2 might be effective in lowering the lipid content, thereby protecting against HFE-induced hyperlipidemia.

Yang Z ，Zhao J ，Li J ，Wang J ，Wang W ... -  《-》