title: Inhibitory effect of reinioside C on vascular smooth muscle cells proliferation induced by angiotensin II via inhibiting NADPH oxidase-ROS-ENK1/2-NF-kappaB-AP-1 pathway.
abstract: The proliferation of vascular smooth muscle cells (VSMCs) induced by angiotensin II (Ang II) plays a vital role in the pathogenesis of arteriosclerosis and restenosis. In the present study, the effect of reinioside C, a main active ingredient of Polygala fallax Hemsl, on proliferation of VSMCs induced by Ang II was investigated. It was found that Ang II (1 microM) markedly stimulated proliferation of VSMCs. Pretreatment of reinioside C (3, 10 or 30 microM) concentration-dependently inhibited the proliferative effect of Ang II. To determine the possible mechanism, NADPH oxidase subunits (Nox-1, Nox-4) mRNA expression, intracellular ROS level, phosphorylation of ERK1/2, NF-kappaB activity, and mRNA expression of AP-1 subunits (c-fos, c-jun) and c-myc were measured. The results demonstrated that reinioside C attenuated Ang II-induced NADPH oxidase mRNA expression, generation of ROS, ERK1/2 phosphorylation, activation of NF-kappaB, and mRNA expression of AP-1 and c-myc in VSMCs in a concentration-dependent manner. The effects of Ang II were also inhibited by diphenyleneiodonium (DPI, the NADPH oxidase inhibitor), PD98059 (the ERK1/2 inhibitor) and pyrrolidine dithiocarbamate (PDTC, the NF-kappaB inhibitor). These results suggest reinioside C attenuates Ang II-induced proliferation of VSMCs by inhibiting NADPH oxidase-ROS-ERK1/2-NF-kappaB-AP-1 pathway.
authors.forename: Dan
authors.initials: D
authors.lastname: Hong
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Bai
authors.forename: Rui-Zheng
authors.initials: RZ
authors.lastname: Shi
authors.forename: Gui-Shan
authors.initials: GS
authors.lastname: Tan
authors.forename: Chang-Ping
authors.initials: CP
authors.lastname: Hu
authors.forename: Guo-Gang
authors.initials: GG
authors.lastname: Zhang
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D024202:Electrophoretic Mobility Shift Assay; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D019255:NADPH Oxidases / Q000378:metabolism*; D016328:NF-kappa B / Q000187:drug effects*; D010766:Phosphorylation; D031801:Polygala / Q000737:chemistry; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000187:drug effects*
chemical_list: D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D012503:Saponins; D018808:Transcription Factor AP-1; C530274:reinioside C; D000804:Angiotensin II; D019255:NADPH Oxidases