title: Alisol A 24-Acetate, a Triterpenoid Derived from Alisma orientale, Inhibits Ox-LDL-Induced Phenotypic Transformation and Migration of Rat Vascular Smooth Muscle Cells through Suppressing ERK1/2 Signaling.
abstract: Alisol A 24-acetate, a triterpenoid extracted from Alisma orientale, has shown antiatherosclerotic actions. The purpose of this study was to evaluate the inhibition of alisol A 24-acetate on oxidized low-density lipoprotein (Ox-LDL)-induced phenotypic transformation and migration of rat vascular smooth muscle cells (VSMCs), and to explore the underlying mechanisms. VSMCs were pretreated with alisol A 24-acetate and a specific extracellular signal-regulated kinase (ERK) inhibitor, U0126, and then stimulated with 50 mg/l Ox-LDL in vitro. The expression of VSMC phenotypic marker SM22α was determined using immunocytochemistry, and the migration of VSMCs was detected using a scratch-wound healing assay. The expression of matrix metalloproteinase (MMP)-9, MMP-2, phosphorylated ERK1/2 (pERK1/2) and total ERK was determined. Ox-LDL treatment caused a reduction in SM22α expression, VSMC transformation to the synthetic phenotype, increased MMP-2 and MMP-9 synthesis, the extension of VSMC migration distance and the upregulation of pERK1/2 expression, while the addition of alisol A 24-acetate or U0126 resulted in the elevation of SM22α expression, VSMC transformation to the contractile phenotype, a reduction in MMP-2 and MMP-9 expression, the shortening of cell migration distance and decreased pERK1/2 expression. The results of this study demonstrate that alisol A 24-acetate effectively reverses the phenotypic transformation and inhibits the migration of VSMCs, which may be associated with the suppression of the ERK1/2 signaling pathway.
authors.affiliation: Rehabilitation Hospital affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, China.
authors.forename: Xie-Hua
authors.initials: XH
authors.lastname: Xue
authors.forename: Xiao-Mao
authors.initials: XM
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Tong
authors.initials: T
authors.lastname: Chen
authors.forename: Qing-Ping
authors.initials: QP
authors.lastname: Su
authors.forename: Jing
authors.initials: J
authors.lastname: Tao
authors.forename: Li-Dian
authors.initials: LD
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000378:metabolism; D034902:Alisma / Q000737:chemistry; D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D002783:Cholestenones / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008077:Lipoproteins, LDL / Q000633:toxicity*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010641:Phenotype; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D000199:Actins; D002783:Cholestenones; D008077:Lipoproteins, LDL; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; C457233:alisol A 24-acetate; C099252:oxidized low density lipoprotein; C498862:Acta2 protein, rat; C535149:Mapk1 protein, rat; C522363:Mmp2 protein, rat; C572337:Mmp9 protein, rat