title: Inhibitory effects of Dioscin on atherosclerosis and foam cell formation in hyperlipidemia rats.
abstract: Macrophage-derived foam cells are well known for their key role in development of atherosclerosis (AS). The present study aimed to examine whether dioscin exerts anti-atherosclerotic activity and inhibits foam cell formation. A high-fat induced AS model and ox-LDL treated macrophages were established and received treatment of dioscin. Anti-atherosclerotic activity in vivo was assessed by atherosclerotic lesions size and aortic lipid contents. Macrophage formed foam cells were positively identified by oil red o staining. Moreover, the expression of LOX-1 and NF-κB in aorta tissue and macrophages was examined by western blotting assay. Our results showed that dioscin not only reduced the levels of plasma lipid, TNF-a, IL-1β and IL-6, but also inhibited atherosclerotic development in AS rats, as evidenced by decreased atherosclerotic lesions size and aortic lipid level. In vitro study revealed dioscin directly reduced foam cell formation, decreased intracellular cholesterol accumulation and lowered TNF-a, IL-1β and IL-6 secretion in ox-LDL treated macrophages. Interestingly, further work found dioscin significantly reduced expression of LOX-1 and NF-κB in the aortic tissue and ox-LDL treated macrophages. In summary, our study was the first to confirm anti-atherosclerotic activity of dioscin in vivo and vitro. Moreover, the other important finding is dioscin mediated ox-LDL/LOX-1/NF-κB regulated contributions to the attenuate macrophage ox-LDL uptake and AS.
authors.affiliation: Department of Rheumatology, The Third Affiliated Hospital of Anhui Medical University, Hefei, 230032, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Rheumatology, The Third Affiliated Hospital of Anhui Medical University, Hefei, 230032, China.
authors.forename: Li-Ya
authors.initials: LY
authors.lastname: He
authors.affiliation: Anhui Provincial Hospital, Hefei, China.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Shen
authors.affiliation: Department of Pharmacy, The Third Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. liruilin0986@hotmail.com.
authors.forename: Rui-Lin
authors.initials: RL
authors.lastname: Li
authors.affiliation: Department of Rheumatology, The Third Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. yjlhefei@163.com.
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Yang
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005487:Foam Cells / Q000187:drug effects* / Q000378:metabolism; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051127:Scavenger Receptors, Class E / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; C019357:dioscin; D002784:Cholesterol; D004144:Diosgenin
keywords: Atherosclerosis; Dioscin; Foam cell; LOX-1; ox-LDL