title: Chlorogenic acid protects against atherosclerosis in ApoE-/- mice and promotes cholesterol efflux from RAW264.7 macrophages.
abstract: Chlorogenic acid (CGA) is one of the most abundant polyphenols in the human diet and is suggested to be a potential antiatherosclerotic agent due to its proposed hypolipidemic, anti-inflammatory and antioxidative properties. The aim of this study was to evaluate the effect of CGA on atherosclerosis development in ApoE(-/-) mice and its potential mechanism. ApoE(-/-) mice were fed a cholesterol-rich diet without (control) or with CGA (200 and 400 mg/kg) or atorvastatin (4 mg/kg) for 12 weeks. During the study plasma lipid and inflammatory parameters were determined. Treatment with CGA (400 mg/kg) reduced atherosclerotic lesion area and vascular dilatation in the aortic root, comparable to atorvastatin. CGA (400 mg/kg) also significantly decreased plasma levels of total cholesterol, triglycerides and low-density lipoprotein-cholesterol as well as inflammatory markers. Supplementation with CGA or CGA metabolites-containing serum suppressed oxidized low-density lipoprotein (oxLDL)-induced lipid accumulation and stimulated cholesterol efflux from RAW264.7 cells. CGA significantly increased the mRNA levels of PPARγ, LXRα, ABCA1 and ABCG1 as well as the transcriptional activity of PPARγ. Cholesterol efflux assay showed that three major metabolites, caffeic, ferulic and gallic acids, significantly stimulated cholesterol efflux from RAW264.7 cells. These results suggest that CGA potently reduces atherosclerosis development in ApoE(-/-) mice and promotes cholesterol efflux from RAW264.7 macrophages. Caffeic, ferulic and gallic acids may be the potential active compounds accounting for the in vivo effect of CGA.
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Chongming
authors.initials: C
authors.lastname: Wu
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Luan
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xiaopo
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Sun
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Guo
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000097:blood / Q000235:genetics; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000097:blood / Q000235:genetics; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D000069059:Atorvastatin / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002109:Caffeic Acids / Q000302:isolation & purification; D002460:Cell Line; D002726:Chlorogenic Acid / Q000737:chemistry / Q000494:pharmacology*; D002784:Cholesterol / Q000009:adverse effects / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003373:Coumaric Acids / Q000302:isolation & purification; D059305:Diet, High-Fat / Q000009:adverse effects; D005707:Gallic Acid / Q000302:isolation & purification; D015870:Gene Expression; D008074:Lipoproteins / Q000097:blood / Q000235:genetics; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors / Q000097:blood; D000071518:Liver X Receptors; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D057093:Orphan Nuclear Receptors / Q000097:blood / Q000235:genetics; D047495:PPAR gamma / Q000097:blood / Q000235:genetics; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation / Q000187:drug effects
chemical_list: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D000924:Anticholesteremic Agents; D001057:Apolipoproteins E; D000069059:Atorvastatin; D002109:Caffeic Acids; D002726:Chlorogenic Acid; D002784:Cholesterol; D008078:Cholesterol, LDL; D003373:Coumaric Acids; D005707:Gallic Acid; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D014280:Triglycerides; C577833:Abca1 protein, mouse; C487540:ABCG1 protein, mouse; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; C099252:oxidized low density lipoprotein; C004999:ferulic acid; C040048:caffeic acid