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Icariin delays homocysteine-induced endothelial cellular senescence involving activation of the PI3K/AKT-eNOS signaling pathway.
MedLine Citation:
PMID:  23336586     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Context: Homocysteine-induced endothelial cellular senescence may contribute to some cardiovascular disorders. Icariin (ICA), a flavonoid derived from Epimedium sagittatum Maxim. (Berberidaceae), has been reported to increase production of nitric oxide (NO) and reduce reactive oxygen species (ROS) levels in human umbilical vein endothelial cells (HUVECs). Objective: To observe the effects of ICA on homocysteine-induced senescence and the underlying mechanisms in HUVECs. Materials and methods: ICA at concentrations of 0.1, 1, and 5 μM was added into homocysteine pretreated HUVECs. Cellular senescence was assayed by senescence-associated β-galactosidase (SA-β-gal) staining and cumulative population doublings (CPDs). ICA (5 μM) was given orally to homocysteine-treated rats, luminal surface of aortic artery of rats was subjected to SA-β-gal staining. Protein expression was measured by western blot. Results: Homocysteine significantly increased cellular senescence both in vitro and in vivo. After treatment by ICA, the percentage of SA-β-gal-positive cells, and the ROS level significantly decreased. The CPDs were partially restored. ICA also significantly reduced the mean density of SA-β-gal staining in vivo. We found that NO production and phosphorylation of AKT, ERK, and endothelial NO synthase (eNOS) were elevated by ICA in HUVECs. Furthermore, the increased level of NO production was fully abolished by the phosphatidylinositol-3-kinase (PI3K) inhibitor wortmannin. The mitogen-activated protein kinase (MEK) inhibitor PD98059, which can inhibit phosphorylation of ERK, did not show this ability. Discussion and conclusion: Our results indicate that ICA delays homocyteine-induced endothelial senescence in vitro and in vivo. Activation of PI3K/Akt-eNOS-dependent signaling pathway may be responsible for this efficacy of ICA.
Authors:
Duan Xiao-Hong; Xu Chang-Qin; Huang Jian-Hua; Zhou Wen-Jiang; Sun Bing
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-22
Journal Detail:
Title:  Pharmaceutical biology     Volume:  -     ISSN:  1744-5116     ISO Abbreviation:  Pharm Biol     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9812552     Medline TA:  Pharm Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Institute of Integrated Traditional Chinese and Western Medicine, Huashan Hospital, Fudan University , Shanghai , China.
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