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Title 

Obovatol from Magnolia obovata inhibits vascular smooth muscle cell proliferation and intimal hyperplasia by inducing p21Cip1

 

일 후박에서 분리한 오보바톨의 혈관 협착 억제 효과 및 기전 규명

Authors 

Y LimJ S KwonD W KimS H LeeR K ParkJ J LeeJ T HongH S YooByoung-Mog KwonY P Yun

Publisher 

Elsevier

Issue Date 

2010

Citation 

Atherosclerosis, vol. 210, no. 2, pp. 372-380

Keywords 

AngioplastyCarotid arteriesObovatolP21Cip1RestenosisVascular smooth muscle cell

Abstract 

Aims: Obovatol is isolated from Magnolia obovata leaves and this active component has various pharmacological properties such as anti-oxidant, anti-platelet, anti-fungal and anti-inflammatory activities. In the present study, we investigated the inhibitory effects of obovatol on in vitro vascular smooth muscle cell (VSMC) proliferation and in vivo neointimal formation in a rat carotid artery injury model. Methods and results: Obovatol (1-5μM) exerted concentration-dependent inhibition on platelet-derived growth factor (PDGF)-BB-induced rat VSMC proliferation, without exhibiting any cellular toxicity or apoptosis, as determined by cell count, [3H]thymidine incorporation and Annexin-V-binding analyses. Treatment with obovatol blocked the cell cycle in G1 phase by down-regulating the expression of cyclins and CDKs, and selectively up-regulating the expression of p21Cip1, a well-known CDK inhibitor. Effects of perivascular delivery of obovatol were assessed 14 days after injury. The angiographic mean luminal diameters of the obovatol-treated groups (100μg and 1mg: 0.78±0.06 and 0.77±0.07AU, respectively) were significantly larger than that of the control group (0.58±0.07AU). The obovatol-treated groups (100μg and 1mg: 0.14±0.04 and 0.09±0.03mm2, respectively) showed significant reduction in neointimal formation versus the control group (0.17±0.02mm2). Immunohistochemical staining demonstrated strong expression of p21Cip1 in the neointima of the obovatol-treated groups. Conclusions: These data suggest that obovatol inhibits VSMC proliferation by perturbing cell cycle progression, possibly due to activation of p21Cip1 pathway. These results also show that obovatol may have potential as an anti-proliferative agent for the treatment of restenosis and atherosclerosis.

ISSN 

0021-9150

Link 

http://dx.doi.org/10.1016/j.atherosclerosis.2009.11.037

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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