title: Rutaecarpine suppresses atherosclerosis in ApoE-/- mice through upregulating ABCA1 and SR-BI within RCT.
abstract: ABCA1 and scavenger receptor class B type I (SR-BI)/CD36 and lysosomal integral membrane protein II analogous 1 (CLA-1) are the key transporter and receptor in reverse cholesterol transport (RCT). Increasing the expression level of ABCA1 and SR-BI/CLA-1 is antiatherogenic. The aim of the study was to find novel antiatherosclerotic agents upregulating expression of ABCA1 and SR-BI/CLA-1 from natural compounds. Using the ABCA1p-LUC and CLA-1p-LUC HepG2 cell lines, we found that rutaecarpine (RUT) triggered promoters of ABCA1 and CLA-1 genes. RUT increased ABCA1 and SR-BI/CLA-1 expression in vitro related to liver X receptor alpha and liver X receptor beta. RUT induced cholesterol efflux in RAW264.7 cells. ApoE-deficient (ApoE(-/-)) mice treated with RUT for 8 weeks showed ∼68.43, 70.23, and 85.56% less en face lesions for RUT (L), RUT (M), and RUT (H) groups, respectively, compared with the model group. Mouse macrophage-specific antibody and filipin staining indicated that RUT attenuated macrophages and cholesterol accumulations in atherosclerotic lesions, respectively. Additionally, ABCA1 and SR-BI expression was highly induced by RUT in livers of ApoE(-/-) mice. Meanwhile, RUT treatment significantly increased the fecal (3)H-cholesterol excretion, which demonstrated that RUT could promote RCT in vivo. RUT was identified to be a candidate that protected ApoE(-/-) mice from developing atherosclerosis through preferentially promoting activities of ABCA1 and SR-BI within RCT.
authors.affiliation: Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Yanni
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: He
authors.affiliation: Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Ningyu
authors.initials: N
authors.lastname: Zhu
authors.affiliation: Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Jikai
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Yexiang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Yongzhen
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Li
authors.affiliation: Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Lai
authors.affiliation: Sir Runrun Shaw Hospital of Zhejiang University, Hangzhou, Zhejiang Province 310016, China.
authors.forename: Murui
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Hong
authors.affiliation: Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Jiang
authors.affiliation: Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Shuyi
authors.initials: S
authors.lastname: Si
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D026121:Indole Alkaloids / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011799:Quinazolines / Q000494:pharmacology*; D000067996:RAW 264.7 Cells; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism*; D052999:Quinazolinones
chemical_list: D064286:ATP Binding Cassette Transporter 1; D001057:Apolipoproteins E; D026121:Indole Alkaloids; D011799:Quinazolines; D051122:Scavenger Receptors, Class B; C577836:ABCA1 protein, human; C577833:Abca1 protein, mouse; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; C028632:rutecarpine; D052999:Quinazolinones
keywords: ATP binding cassette transporter A1; apolipoprotein E deficient; reverse cholesterol transport; scavenger receptor class B type I