Effect of silibinin on endothelial dysfunction and ADMA levels in obese diabetic mice

Cardiovascular Diabetology

Original Investigation

Vincenzo Urso¹  Salvatore Salomone¹  Ilias Siarkos¹  Fabio Galvano²  Valeria Sorrenti²  Giovanni Li Volti³  Federico Salamone⁴  Andrea Mangiameli⁴ 

[1] Department of Clinical and Molecular Biomedicine, University of Catania, Catania, Italy;Department of Drug Sciences, University of Catania, Catania, Italy;Department of Drug Sciences, University of Catania, Catania, Italy;Department of Cardiac Surgery, San Donato Institute, San Donato Milanese (MI), Italy;Department of Internal Medicine, University of Catania, Catania, Italy;

关键词: diabetes;    silibinin;    db/db;    endothelial dysfunction;    ADMA;    vascular reactivity;   

DOI  :  10.1186/1475-2840-10-62

 received in 2011-04-20, accepted in 2011-07-14,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundCardiovascular diseases (CVD) in diabetic patients have endothelial dysfunction as a key pathogenetic event. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), plays a pivotal role in endothelial dysfunction. Different natural polyphenols have been shown to preserve endothelial function and prevent CVD. In this study, we assessed the effect of silibinin, a widely used flavonolignan from milk thistle, on ADMA levels and endothelial dysfunction in db/db mice.MethodsEight-week-old db/db mice were administrated a 20 mg/Kg i.p. daily dose of silibinin (n = 6) or vehicle (n = 6) for four weeks. Heterozygous lean db/m mice served as control. Plasma, aorta and liver ADMA levels were determined by ELISA. Vascular reactivity to phenilephrine (PE), acetylcholine (ACh), sodium nitroprusside (SNP) and ADMA was assessed in isolated aortic segments, in wire myograph.ResultsPlasma and aorta ADMA levels were higher in db/db than in control lean mice. Silibinin administration markedly decreased plasma ADMA; consistently, aorta ADMA was reduced in silibinin-treated animals. Plasma and aorta ADMA levels exhibited a positive correlation, whereas liver ADMA was inversely correlated with both plasma and aorta ADMA concentrations. Endothelium-(NO)-dependent vasodilatation to ACh was impaired in db/db mice and was restored in the silibinin group, in accordance with the observed reduction of plasma and vascular levels of ADMA. Endothelium-independent vasodilatation to SNP was not modified by silibinin administration; contractile tone induced in isolated aorta from db/db mice by challenging with exogenous ADMA was not affected by the treatment.ConclusionsSilibinin markedly improves endothelial dysfunction in db/db mice by reducing circulating and vascular ADMA levels. Clinical studies are warranted to assess the efficacy of silibinin for cardiovascular protection.

【 授权许可】

Unknown   
© Volti et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.