Polygonum viviparum L. induces vasorelaxation in the rat thoracic aorta via activation of nitric oxide synthase in endothelial cells

BMC Complementary and Alternative Medicine

Chien-Ming Hu³  Hui-Wen Cheng¹  Joe-Sharg Li²  Khoot-Peng Cheah²  Wen-Yu Yu²  Jung-Su Chang⁴  Ming-Long Chang² 

[1] School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei Taiwan;Emergency Department, Taipei Medical University Hospital, 252 Wu-Xing Street, Taipei 110, Taiwan;Medical University, 250 Wu-Xing Street, Taipei 110, Taiwan;School of Nutrition and Health Sciences, Taipei Medical University, Taipei Taiwan

关键词: HUVECs;    eNOS;    cGMP;    Vasorelaxation;    Aorta;    Polygonum viviparum L;   

Others  :  1220170
DOI  :  10.1186/1472-6882-14-150

 received in 2012-09-21, accepted in 2014-04-17,  发布年份 2014

【 摘 要 】

Background

In the past several decades, Polygonum viviparum L. (PV) was reported to have antibacterial, antiulcer, antioxidant, antitumor, anti-inflammatory, and antiarthritic properties. The anti-inflammatory pathway was recently elucidated through cytosolic nuclear factor E2-related factor 2 (Nrf2) activation and heme oxygenase (HO)-1 protein expression. PV is a perennial herb and widely distributed in high-elevation mountain regions, such as the Tibetan Plateau. In Tibetan traditional medicine, PV is usually used to boost the blood circulation to dissipate blood stasis. Therefore, this study focused on how PV improves the vascular circulation and acts on vascular tissues.

Methods

In this study, we isolated aortas from Sprague-Dawley rats (male, weight about 250 ~ 350 g), and detected the effects of PV on phenylephrine (PE)-induced contraction and cyclic guanosine 3′,5′-monophosphate (cGMP) formation using aortic rings. In addition, human umbilical vein endothelial cells (HUVECs) were used to exam nitric oxygen (NO) synthase (NOS) activity by directly measuring NO production in the culture medium. Endothelial (e) NOS phosphorylation, and cytosolic Nrf2 and HO-1 expressions were measured using a Western blot analysis.

Results

PV dose-dependently relaxed PE-induced contractions in endothelial-intact but not -denuded aorta. The concentration to produce 50% relaxation was 22.04 ± 1.77 μg/ml. PV-induced vasorelaxation was markedly blocked by pretreatment with N^G-nitro-_L-arginine methyl ester (L-NAME), an NOS inhibitor, methylene blue (MB), a guanylyl cyclase inhibitor, and hemoglobin, an NO scavenger. PV increased cGMP formation; however, this effect was also suppressed by co-pretreatment with L-NAME, MB, hemoglobin, and Ca²⁺-free medium. In HUVECs, PV increased NO formation, which was greatly attenuated by NOS inhibitors (L-NAME and L-NMMA) and by removing extracellular Ca²⁺ and chelating intracellular Ca²⁺ with BAPTA-AM. In addition, PV promoted eNOS phosphorylation, Nrf2 degradation, and HO-1 protein expression according to a Western blot analysis.

Conclusions

The results suggest that PV possesses vasorelaxing action in an endothelium-dependent manner and works through activating Ca²⁺/calmodulin- dependent NO synthesis; when NO is released and then transferred to smooth muscle cells, NO activates guanylyl cyclase and increases cGMP formation, ultimately resulting in vasorelaxation. Thus, PV can be considered for application as a potential therapeutic approach for vascular-associated disorders.

【 授权许可】

   
2014 Chang et al.; licensee BioMed Central Ltd.

【 图 表 】

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