Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
J Ethnopharmacol. 2018 Mar 1;213:81-91. doi: 10.1016/j.jep.2017.11.004. Epub 2017 Nov 10.
Xylocarpus moluccensis (Lamk.) M. Roem of family Meliaceae has triterpenoids rich fruits. Triterpenoids have been known to possess cardioprotection and anti-atherosclerotic activities (Han and Bakovic, 2015; Wu et al., 2009). Standardized fraction of these fruits exhibited anti-dyslipidemic (Srivastava et al., 2015), anti-inflammatory (Ravangpai et al., 2011) and CNS depressant activity (Sarker et al., 2007). However, there is no report in the literature on its cardiovascular effects.
The present study was undertaken to assess vasoprotective, anti-atherosclerotic and further examine the anti-dyslipidemic effect of the standardized fraction of Xylocarpus moluccensis (F018) fruits in the mechanical injury and high fat diet (HFD) induced dyslipidemic/ atherosclerosis models.
Guinea pigs were fed 0.08% cholesterol + 15% fat diet for 3 weeks, while ApoE KO mice were fed high fat diet for 18 weeks to induce dyslipidemia and atherosclerosis. A combination of balloon injury and high fat diet (1% cholesterol, 6% peanut oil) for 5 weeks was used to accelerate atherosclerosis in NZW rabbits. F018 was administered once daily by oral route in guinea pigs (10, 25 or 50mg/kg/day for 3 weeks), ApoE KO mice (50mg/kg/day for 6 weeks) and in NZW rabbit (25mg/kg/day for 5 weeks) to monitor its effect on dyslipidemia, vasoreactivity and plaque composition by using standard methodologies.
F018 treatment in guinea pigs (25 and 50mg/kg/day), ApoE mice (50mg/kg/day) and rabbits (25mg/kg/day) significantly reduced plasma lipids and improved ACh induced vasorelaxation. Anti-dyslipidemic effect of F018 seems to be due to the modulation of enterohepatic genes involved in the cholesterol absorption and excretion. Moreover, significant improvement in the acetylcholine (ACh) induced vasorelaxation was accompanied with reduced inflammatory burden and enhanced activation of eNOS in ApoE mice aortic tissue. Similarly inflammatory cytokines, immunolabeling of macrophage marker (CD68) and MMP-9 were reduced along with augmentation in vascular smooth muscle cells and collagen type I and III in the mechanically injured iliac artery segment in the rabbits.
Altogether, F018 preserved vasoreactivity, reduced atherosclerotic plaque progression and enhanced plaque stability by reducing lipids, inflammatory cytokines, improving endothelial function and collagen content.
桃金娘科植物 Xylocarpus moluccensis（Lamk.）M. Roem 的果实富含三萜类化合物。三萜类化合物已被证明具有心脏保护和抗动脉粥样硬化作用（Han 和 Bakovic，2015；Wu 等人，2009）。这些果实的标准化部分表现出抗血脂异常（Srivastava 等人，2015）、抗炎（Ravangpai 等人，2011）和中枢神经系统抑制活性（Sarker 等人，2007）。然而，文献中没有关于其心血管作用的报道。
本研究旨在评估 Xylocarpus moluccensis（F018）果实标准化部分的血管保护、抗动脉粥样硬化作用，并进一步研究其在机械损伤和高脂肪饮食（HFD）诱导的血脂异常/动脉粥样硬化模型中的抗血脂异常作用。
豚鼠喂食 0.08%胆固醇+15%脂肪饮食 3 周，ApoE KO 小鼠喂食高脂肪饮食 18 周诱导血脂异常和动脉粥样硬化。使用球囊损伤和高脂肪饮食（1%胆固醇，6%花生油）联合 5 周加速新西兰白兔的动脉粥样硬化。F018 通过口服途径每天一次给药，剂量分别为豚鼠（10、25 或 50mg/kg/天，持续 3 周）、ApoE KO 小鼠（50mg/kg/天，持续 6 周）和新西兰白兔（25mg/kg/天，持续 5 周），以使用标准方法监测其对血脂异常、血管反应性和斑块组成的影响。
F018 治疗豚鼠（25 和 50mg/kg/天）、ApoE 小鼠（50mg/kg/天）和兔子（25mg/kg/天）可显著降低血浆脂质并改善 ACh 诱导的血管舒张。F018 的抗血脂异常作用似乎是由于调节了参与胆固醇吸收和排泄的肠肝基因。此外，ApoE 小鼠主动脉组织中 ACh 诱导的血管舒张明显改善伴随着炎症负担减轻和 eNOS 激活增强。同样，在机械损伤的髂动脉段中，炎症细胞因子、巨噬细胞标志物（CD68）的免疫标记物和 MMP-9 的减少伴随着血管平滑肌细胞和胶原 I 和 III 的增加。
总之，F018 通过降低脂质、炎症细胞因子、改善内皮功能和胶原含量来保持血管反应性、减少动脉粥样硬化斑块进展并增强斑块稳定性。
