Frediani Brant Nayara Mercedes, Mourão Gasparotto Francielly, de Oliveira Araújo Valdinei, Christian Maraschin Jhonatan, Lima Ribeiro Rita de Cassia, Botelho Lourenço Emerson Luiz, Cardozo Junior Euclides Lara, Gasparotto Junior Arquimedes
Instituto de Ciências Biológicas, Médicas e da Saúde, Universidade Paranaense, PR, Brazil.
Instituto de Ciências Exatas, Agrárias, Tecnológicas e Geociências, Universidade Paranaense, Umuarama, PR, Brazil.
J Ethnopharmacol. 2014 Jun 11;154(2):419-27. doi: 10.1016/j.jep.2014.04.019. Epub 2014 Apr 18.
Although Casearia sylvestris Swartz is used in Brazilian folk medicine to treat obesity, no study has been conducted to evaluate the effects of this species in an experimental model of dyslipidemia and atherosclerosis. So, the aim of this study was to evaluate possible hypolipemiant and antiatherogenic activity of the methanolic extract obtained from Casearia sylvestris (MECS) using Swiss and C57BL/6 LDLr-null mice undergoing high fat diet (HFD).
Dyslipidemia and atherogenesis were induced by the administration of commercial HFD for 4 weeks. The MECS was administered orally at doses of 250 and 500mg/kg, once a day, for two weeks, starting from the 2nd week of HFD. The gain in body weight and systolic blood pressure (SBP) were measured weekly over the four week study. At the end of the experiments the levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C) were measured by colorimetric method. Aldosterone, vasopressin and angiotensin converting enzyme (ACE) activity were also evaluated in collected serum. The renal function, atherogenic index serum (AIS) and in vitro antiplatelet activity were investigated. Additionally, histopathological analyzes were performed to determine the intima-media thickness (IMT) and intima media ratio (IMR) in aorta samples.
The HFD induced dyslipidemia and major structural changes in the aortic wall, including raising of the systolic blood pressure in LDLr-null mice. In addition, we observed an increase in lipid peroxidation accompanied by a reduction of serum nitrite. The treatment with MECS was able to prevent the increase of SBP, TC, LDL-C, VLDL-C and triglycerides levels and increase HDL-C in Swiss and LDLr-null mice. These effects were accompanied by a significant reduction in oxidative stress. Moreover, AIS, IMT and IMR were significantly reduced in MECS-treated mice, and the extract was able to reduce platelet aggregation in vitro.
This study demonstrated that MECS reduces the serum lipids and oxidative stress when orally administered to Swiss and LDLr-null mice. In addition, it was able to prevent arterial thickening induced by HFD and to inhibit platelet aggregation in vitro.
尽管巴西民间医学使用野生嘉赐树治疗肥胖症,但尚未有研究评估该物种在血脂异常和动脉粥样硬化实验模型中的作用。因此,本研究的目的是使用高脂饮食(HFD)喂养的瑞士小鼠和C57BL/6 LDLr基因敲除小鼠,评估从野生嘉赐树中获得的甲醇提取物(MECS)可能的降血脂和抗动脉粥样硬化活性。
通过给予商业高脂饮食4周诱导血脂异常和动脉粥样硬化形成。从高脂饮食的第2周开始,以250和500mg/kg的剂量每天口服一次MECS,持续两周。在为期四周的研究中,每周测量体重增加和收缩压(SBP)。实验结束时,采用比色法测量甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和极低密度脂蛋白胆固醇(VLDL-C)的水平。还对收集的血清中的醛固酮、血管加压素和血管紧张素转换酶(ACE)活性进行了评估。研究了肾功能、动脉粥样硬化指数血清(AIS)和体外抗血小板活性。此外,进行组织病理学分析以确定主动脉样本的内膜中层厚度(IMT)和内膜中层比率(IMR)。
高脂饮食诱导了血脂异常和主动脉壁的主要结构变化,包括LDLr基因敲除小鼠收缩压升高。此外,我们观察到脂质过氧化增加,同时血清亚硝酸盐减少。用MECS治疗能够预防瑞士小鼠和LDLr基因敲除小鼠的收缩压、总胆固醇、低密度脂蛋白胆固醇、极低密度脂蛋白胆固醇和甘油三酯水平升高,并增加高密度脂蛋白胆固醇。这些作用伴随着氧化应激的显著降低。此外,MECS治疗的小鼠的动脉粥样硬化指数、内膜中层厚度和内膜中层比率显著降低,并且该提取物能够在体外减少血小板聚集。
本研究表明,口服给予瑞士小鼠和LDLr基因敲除小鼠MECS可降低血脂和氧化应激。此外,它能够预防高脂饮食诱导的动脉增厚,并在体外抑制血小板聚集。