Laboratory of Electrophysiology and Cardiovascular Pharmacology, Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil.
University Center of Grande Dourados, Dourados, MS, Brazil.
Phytomedicine. 2017 Oct 15;34:162-170. doi: 10.1016/j.phymed.2017.08.012. Epub 2017 Aug 17.
Ilex paraguariensis A. St. Hil. var. paraguariensis (Aquifoliaceae) popularly known as 'mate' is an important species native to South America. Despite numerous studies showing significant antioxidant and lipid lowering properties, the antiatherosclerotic mechanisms of this species remain unknown.
To evaluate the possible antiatherosclerotic effects of a butanolic fraction (n-BFIP) obtained from I. paraguariensis and to investigate the molecular mechanisms involved in this activity.
First, n-BFIP was obtained from the hydroalcoholic extract and a detailed phytochemical investigation about its main secondary metabolites was performed. Then, during 8 experimental weeks, rabbits received diet supplemented with 1% cholesterol (CRD). After 4 weeks of CDR, animals were redistributed into five groups (n = 6) and treated (p.o.) with n-BFIP (10, 30 and 100 mg/kg), simvastatin (5 mg/kg), or vehicle (filtered water, 1 ml/kg) once daily for 4 weeks. An additional group was fed with cholesterol-free diet and treated with vehicle. At the end of 8 weeks, serum samples were obtained for the measurement of serum lipids, lipid and protein oxidation and indirect nitric oxide levels. In addition, serum IL-1β, IL-6, sICAM-1, sVCAM-1, and intracellular cGMP levels in rabbit aortic rings were measured. Samples from the aortic arch and thoracic segment were collected for histopathological analysis.
CRD induced oxidative and nitrosative stress and increased serum lipids, IL-1β, IL-6, sICAM-1, and sVCAM-1 levels. In addition, structural changes in the intima layers of different arterial branches were also found. Although it did not change serum lipids, n-BFIP reverted oxidative and nitrosative stress and reduced IL-1β, IL-6, sICAM-1, and sVCAM-1 levels, besides to increasing intracellular levels of cGMP in vitro. In addition, the formation of atherosclerotic plaques was reduced to values close to those of animals fed with cholesterol-free diet.
A 4-week n-FBIP treatment reduces the progression of the atherosclerotic disease in New Zealand rabbits. These effects are associated with an attenuation of oxidative and nitrosative stress, affecting IL-1β, IL-6, sICAM-1 and sVCAM-1 levels.
巴拉圭冬青（Aquifoliaceae）的 Ilex paraguariensis A. St. Hil. var. paraguariensis 俗称“马黛茶”，是一种原产于南美洲的重要物种。尽管有许多研究表明它具有显著的抗氧化和降血脂特性，但该物种的抗动脉粥样硬化机制尚不清楚。
评估从 I. paraguariensis 获得的正丁醇部分（n-BFIP）的可能抗动脉粥样硬化作用，并研究其活性涉及的分子机制。
首先，从水醇提取物中获得 n-BFIP，并对其主要次生代谢物进行详细的植物化学研究。然后，在 8 周的实验期间，兔子接受添加 1%胆固醇（CRD）的饮食。在 CDR 4 周后，动物被重新分配到五组（每组 n=6），并每天（p.o.）用 n-BFIP（10、30 和 100mg/kg）、辛伐他汀（5mg/kg）或载体（过滤水，1ml/kg）处理 4 周。另外一组喂食无胆固醇饮食并接受载体处理。8 周后，采集血清样本以测量血清脂质、脂质和蛋白质氧化以及间接一氧化氮水平。此外，还测量了兔主动脉环中血清白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、可溶性细胞间黏附分子-1（sICAM-1）、可溶性血管细胞黏附分子-1（sVCAM-1）和细胞内环鸟苷酸（cGMP）水平。收集主动脉弓和胸段的样本进行组织病理学分析。
CRD 诱导氧化和硝化应激，增加血清脂质、IL-1β、IL-6、sICAM-1 和 sVCAM-1 水平。此外，还发现不同动脉分支的内膜层结构发生变化。虽然 n-BFIP 没有改变血清脂质，但它能逆转氧化和硝化应激，降低 IL-1β、IL-6、sICAM-1 和 sVCAM-1 水平，同时还能增加体外细胞内 cGMP 水平。此外，动脉粥样硬化斑块的形成减少到接近喂食无胆固醇饮食的动物的值。
4 周 n-FBIP 治疗可降低新西兰兔动脉粥样硬化疾病的进展。这些作用与氧化和硝化应激的减轻有关，影响 IL-1β、IL-6、sICAM-1 和 sVCAM-1 水平。
