title: Icariin inhibits oxidized low-density lipoprotein-induced proliferation of vascular smooth muscle cells by suppressing activation of extracellular signal-regulated kinase 1/2 and expression of proliferating cell nuclear antigen.
abstract: Icariin, a flavonoid isolated from the traditional Chinese herbal medicine Epimedium brevicornum Maxim, has been shown to possess anti-inflammatory, anti‑oxidant and anti-atherosclerotic activities in vivo and in vitro. The aim of the present study was to investigate the effects of icariin on oxidized low‑density lipoprotein (ox-LDL)-induced proliferation of vascular smooth muscle cells (VSMCs) and the possible underlying mechanism. VSMCs were cultured and pre‑treated with various concentrations of icariin (0, 10, 20 or 40 µm) prior to stimulation by ox‑LDL (50 µg/ml). Cell proliferation was evaluated by an MTT assay. Flow cytometry was used to study the influence of icariin on the cell cycle. Proliferating cell nuclear antigen (PCNA) expression and phosphorylation levels of extracellular signal-regulated kinase (ERK)1/2 were detected by western blot analysis. The results indicated that icariin significantly inhibited ox‑LDL‑induced proliferation of VSMCs and phosphorylation of ERK1/2. Furthermore, icariin also blocked the ox‑LDL‑induced cell‑cycle progression at G1/S‑interphase and downregulated the expression of PCNA in VSMCs. In conclusion, the present study indicated for the first time that icariin reduced the amount of ox‑LDL‑induced proliferation of VSMCs through suppression of PCNA expression and inactivation of ERK1/2.
authors.affiliation: Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yanwu
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Mengtong
authors.initials: M
authors.lastname: Yan
authors.affiliation: Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yadi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Ren
mesh_terms: D050197:Atherosclerosis / Q000188:drug therapy; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D008077:Lipoproteins, LDL; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
chemical_list: D005419:Flavonoids; D008077:Lipoproteins, LDL; D018809:Proliferating Cell Nuclear Antigen; C099252:oxidized low density lipoprotein; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C056599:icariin