title: Fumigaclavine C activates PPARγ pathway and attenuates atherogenesis in ApoE-deficient mice.
abstract: OBJECTIVE
  To develop alternative therapeutic strategy that reduces hypercholesterolemia, inflammation and atherosclerosis, we investigate if fumigaclavine C (FC), an indole alkaloid in structure, has anti-atherosclerosis function, and if so, what is the mechanism involved.
  
  
  RESULTS
  We used ApoE-deficient (ApoE(-/-)) mice as an atherosclerosis model to examine if FC reduced aorta lesion size and improved serum lipid profiles. ApoE(-/-) mice at 6 weeks of age were fed on a western diet for 10 weeks before FC was administrated (5, 10 and 20 mg/kg) by gavage daily for additional 4 weeks. The mice were sacrificed at 20 weeks of age for examination. The atherosclerotic lesions were assessed with Oil Red O staining in the whole aorta and aortic sinus. Serum levels of triglycerides (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-c) and low density lipoprotein cholesterol (LDL-c) were determined enzymatically. Mouse macrophages were examined for lipid droplets inside cells. FC's effect on PPARγ and PPARγ signaling pathway were further investigated by western blot and luciferase assay. We found that FC decreased atherosclerotic lesion formation in ApoE(-/-) mice in a dose-dependent manner. Also FC improved lipid profiles in ApoE(-/-) mice and reduced the foam cell numbers of peritoneal macrophages. FC stimulated PPARγ signaling pathway proteins both in vitro and in vivo. FC enhanced PPARγ transactivation activity assayed by a PPRE reporter system.
  
  
  CONCLUSIONS
  Our data indicated that FC activated PPARγ signaling pathway as well as its downstream proteins and had an effective role of anti-atherosclerosis.
authors.affiliation: Nanjing University School of Medicine, Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093, China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China.
authors.forename: Rong Hui
authors.initials: RH
authors.lastname: Du
authors.affiliation: Nanjing University School of Medicine, Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093, China.
authors.forename: Si Yuan
authors.initials: SY
authors.lastname: Qin
authors.affiliation: Nanjing University School of Medicine, Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093, China.
authors.forename: Lu Sen
authors.initials: LS
authors.lastname: Shi
authors.affiliation: Nanjing University School of Medicine, Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093, China.
authors.forename: Zi Qian
authors.initials: ZQ
authors.lastname: Zhou
authors.affiliation: Nanjing University School of Medicine, Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093, China.
authors.forename: Xi Yu
authors.initials: XY
authors.lastname: Zhu
authors.affiliation: Nanjing University School of Medicine, Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China.
authors.forename: Ren Xiang
authors.initials: RX
authors.lastname: Tan
authors.affiliation: Nanjing University School of Medicine, Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093, China; Jinling Hospital Research Institute of Nephrology, Nanjing University School of Medicine, Nanjing 210008, China. Electronic address: wangsencao@nju.edu.cn.
authors.forename: Wangsen
authors.initials: W
authors.lastname: Cao
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000188:drug therapy*; D004876:Ergot Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use*; D026121:Indole Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000187:drug effects*
chemical_list: D001057:Apolipoproteins E; D004876:Ergot Alkaloids; D026121:Indole Alkaloids; D047495:PPAR gamma; C492995:fumigaclavine C
keywords: ApoE(−/−); Atherosclerosis; Fumigaclavine C; Indole alkaloid; Lipid metabolism; PPARγ pathway