title: Antihyperlipidemic effect of Cyclocarya paliurus (Batal.) Iljinskaja extract and inhibition of apolipoprotein B48 overproduction in hyperlipidemic mice.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, PR China; Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China.
authors: Yonglan
authors: Y
authors: Ma
authors: Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China.
authors: Cuihua
authors: C
authors: Jiang
authors: Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China.
authors: Nan
authors: N
authors: Yao
authors: Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China.
authors: Yue
authors: Y
authors: Li
authors: Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, PR China; Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China.
authors: Qingqing
authors: Q
authors: Wang
authors: College of Forest Resources and Environment, Nanjing Forestry University, Nanjing 210042, Jiangsu Province, PR China.
authors: Shengzuo
authors: S
authors: Fang
authors: College of Forest Resources and Environment, Nanjing Forestry University, Nanjing 210042, Jiangsu Province, PR China.
authors: Xulan
authors: X
authors: Shang
authors: Department of Medicinal Chemistry and Pharmacognosy, and WHO Collaborating Center for Tradition Medicine, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors: Ming
authors: M
authors: Zhao
authors: Department of Medicinal Chemistry and Pharmacognosy, and WHO Collaborating Center for Tradition Medicine, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors: Chuntao
authors: C
authors: Che
authors: Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China; Theragnostic Laboratory, KU Leuven, Campus Gasthuisberg, 3000 Leuven, Belgium.
authors: Yicheng
authors: Y
authors: Ni
authors: Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China. Electronic address: zjwonderful@hotmail.com.
authors: Jian
authors: J
authors: Zhang
authors: Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, PR China; Department of Medicinal Chemistry and Pharmacognosy, and WHO Collaborating Center for Tradition Medicine, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA. Electronic address: chyzq2005@126.com.
authors: Zhiqi
authors: Z
authors: Yin
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D053283:Apolipoprotein B-48 / Q000037:antagonists & inhibitors*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology; D020834:Ethnopharmacology / Q000379:methods; D005979:Glutathione Peroxidase / Q000097:blood; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000737:chemistry / Q000494:pharmacology*; D029525:Juglandaceae / Q000737:chemistry*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D013482:Superoxide Dismutase / Q000097:blood; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D053283:Apolipoprotein B-48; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004365:Drugs, Chinese Herbal; D000960:Hypolipidemic Agents; D008055:Lipids; D010936:Plant Extracts; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: Antihyperlipidemic; Antioxidant; ApoB48; Arjunolic acid (PubChem CID: 73641); Cyclocaric acid B (CAS No. 182315-46-4); Cyclocarya paliurus; Isoquercitrin (PubChem CID: 5280804); Kaempferol-3-O-α-l-rhamnopyranoside (PubChem CID: 5316673); Kaempferol-3-O-β-d-glucuronide (PubChem CID: 5282102); MAPK; Pterocaryoside A (CAS No. 168146-85-8).; Pterocaryoside B (CAS No. 168146-27-8); TNF-α