title: Gastrodin inhibits cell proliferation in vascular smooth muscle cells             and attenuates neointima formation in vivo.
abstract: Vascular smooth muscle cell (VSMC) proliferation plays a critical role in the development of vascular diseases. In the present study, we tested the efficacy and the mechanisms of action of gastrodin, a bioactive component of the Chinese herb Gastrodia elata Bl, in relation to platelet-derived growth factor-BB (PDGF-BB)-dependent cell proliferation and neointima formation after acute vascular injury. Cell experiments were performed with VSMCs isolated from rat aortas. WST and BrdU incorporation assays were used to evaluate VSMC proliferation. Eight-week-old C57BL/6 mice were used for the animal experiments. Gastrodin (150 mg/kg/day) was administered in the animal chow for 14 days, and the mice were subjected to wire injury of the left carotid artery. Our data demonstrated that gastrodin attenuated the VSMC proliferation induced by PDGF-BB, as assessed by WST assay and BrdU incorporation. Gastrodin influenced the S-phase entry of VSMCs and stabilised p27Kip1 expression. In addition, pre-incubation with sinomenine prior to PDGF-BB stimulation led to increased smooth muscle-specific gene expression, thereby inhibiting VSMC dedifferentiation. Gastrodin treatment also reduced the intimal area and the number of PCNA-positive cells. Furthermore, PDGF-BB-induced phosphorylation of ERK1/2, p38 MAPK, Akt and GSK3β was suppressed by gastrodin. Our results suggest that gastrodin can inhibit VSMC proliferation and attenuate neointimal hyperplasia in response to vascular injury. Furthermore, the ERK1/2, p38 MAPK and Akt/GSK3β signalling pathways were found to be involved in the effects of gastrodin.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Zhu
authors.forename: Hongjing
authors.initials: H
authors.lastname: Guan
authors.forename: Changping
authors.initials: C
authors.lastname: Cui
authors.forename: Song
authors.initials: S
authors.lastname: Tian
authors.forename: Da
authors.initials: D
authors.lastname: Yang
authors.forename: Xinan
authors.initials: X
authors.lastname: Wang
authors.forename: Shuming
authors.initials: S
authors.lastname: Zhang
authors.forename: Lang
authors.initials: L
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000077214:Becaplermin; D001592:Benzyl Alcohols / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D058426:Neointima / Q000517:prevention & control*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001592:Benzyl Alcohols; D004365:Drugs, Chinese Herbal; D005960:Glucosides; D009124:Muscle Proteins; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; C045345:gastrodin; D048049:Extracellular Signal-Regulated MAP Kinases