title: Cordycepin attenuates neointimal formation by inhibiting reactive oxygen species-mediated responses in vascular smooth muscle cells in rats.
abstract: We determined the action mechanism of cordycepin, a major bioactive component of Cordyceps militaris, on responses of rat aortic smooth muscle cells (RASMCs) and on vascular disorders, especially neointimal formation. Cordycepin inhibited platelet-derived growth factor-BB (PDGF-BB)-induced RASMCs migration and proliferation in a dose-dependent manner. However, pre-treatment with N(omega)-nitro-L-arginine methyl ester, a nitric oxide synthase (NOS) inhibitor, and 1,3-dipropyl-8-sulphophenylxanthine (DPSPX), an A(1)/A(2) adenosine-receptor antagonist, abolished the inhibitory role of cordycepin. Cordycepin suppressed the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and heat shock protein 27 (Hsp27), but not that of extracellular signal-regulated kinase (ERK) 1/2 in RASMCs stimulated by PDGF-BB. The production of reactive oxygen species (ROS), O(2)(-) and H(2)O(2), induced by PDGF-BB was abolished by the treatment of cordycepin. Moreover, the sprout outgrowth of aortic rings by PDGF-BB was inhibited by cordycepin. In vivo neointimal formation evoked by balloon-injury was significantly attenuated by the administration of cordycepin. These results demonstrate that cordycepin may exert inhibitory effects on PDGF-BB-induced migration and proliferation via interfering with adenosine receptor-mediated NOS pathways, thus resulting in the attenuation of neointima formation. In conclusion, cordycepin may be a potent, promising anti-atherosclerosis agent.
authors.affiliation: Department of Physiology & Immunology, School of Medicine, Konkuk University, Republic of Korea.
authors.forename: Kyung-Jong
authors.initials: KJ
authors.lastname: Won
authors.forename: Su-Chan
authors.initials: SC
authors.lastname: Lee
authors.forename: Chang-Kwon
authors.initials: CK
authors.lastname: Lee
authors.forename: Hwan Myung
authors.initials: HM
authors.lastname: Lee
authors.forename: So Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Zhi
authors.initials: Z
authors.lastname: Fang
authors.forename: Ok Byung
authors.initials: OB
authors.lastname: Choi
authors.forename: Meihua
authors.initials: M
authors.lastname: Jin
authors.forename: Junghwan
authors.initials: J
authors.lastname: Kim
authors.forename: Taekyu
authors.initials: T
authors.lastname: Park
authors.forename: Wahn Soo
authors.initials: WS
authors.lastname: Choi
authors.forename: Si-Kwan
authors.initials: SK
authors.lastname: Kim
authors.forename: Bokyung
authors.initials: B
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D000077214:Becaplermin; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D032661:Cordyceps / Q000737:chemistry*; D003839:Deoxyadenosines / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism; D017539:Tunica Intima / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D003839:Deoxyadenosines; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D017382:Reactive Oxygen Species; D018047:Receptors, Purinergic P1; D000077214:Becaplermin; D019001:Nitric Oxide Synthase; C058120:cordycepin