Anti-atherosclerotic activities of flavonoids from the flowers of Helichrysum arenarium L. MOENCH through the pathway of anti-inflammation
Anti-atherosclerotic activities of flavonoids from the flowers of Helichrysum arenarium L. MOENCH through the pathway of anti-inflammation
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DOI：
10.1016/j.bmcl.2017.04.076
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发表时间：
2017-06-15
影响因子：
2.7
通讯作者：
Wang, Xiaobo
中科院分区：
文献类型：
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作者：
Mao, Zhonghua;Gan, Chunli;Wang, Xiaobo
采用胸主动脉血管环成功建立AS模型，通过血管形态学改变、VSMC增殖及炎症因子VEGF、CRP、JNK 2和p38的表达进行评价。该模型具有成本低、使用方便、建立时间短等优点。此外，我们还研究了沙生蜡菊花中的7个黄酮类化合物：柚皮苷（1）、柚苷（2）、圣草酚（3）、木犀草素（4）、Galuteolin（5）、黄芪甲素（6）、山萘酚（7）的抗AS活性。MOENCH通过检测血管形态学，抑制炎症因子CRP、VEGF、JNK 2、p38的表达。此外，我们研究了这7个黄酮类化合物的抗AS活性，通过检测NO分泌的RAW 264.7细胞响应于LPS。上述炎症因子均参与了AS的形成。通过对所有结果的综合分析，讨论了结构与活性的关系，我们总结了以下结论：化合物1-7对VEGF、CRP、JNK 2、p38和NO的表达均有不同程度的抑制作用，其中黄酮醇苷元的抗炎作用明显强于其苷元，黄酮醇类化合物的抗AS作用强于黄酮类化合物和黄酮类化合物，这意味着3-群可能是有效群。最终我们推测这些化合物的主要抗炎机制是降低CRP的表达，抑制JNK 2和p38的激酶活性，从而抑制MAPK途径，导致NO合成、VEGF表达和内皮粘附因子表达下降。最终，疤痕组织和血管狭窄的形成得到了预防。提示黄酮类化合物具有预防AS形成的作用。(C)2017爱思唯尔有限公司版权所有
We have successfully established AS model using thoracic aortas vascular ring which evaluated by the morphological changes of blood vessels, the proliferation of VSMC, and the expression of inflammation factors VEGF, CRP, JNK2 and p38. This AS model has the advantages of low cost, convenient and short period of established time. Moreover, we investigated the anti-AS activities of 7 flavonoids Narirutin (1), Naringin (2), Eriodictyol (3), Luteolin (4), Galuteolin (5), Astragalin (6), Kaempferol (7) from flowers of Helichrysum arenarium L. MOENCH by examining the vascular morphology, the inhibition on the expression of inflammation factors CRP, VEGF, JNK2, p38. In addition, we investigated the anti-AS activities of these 7 flavonoids by examining NO secretion of RAW264.7 cells in response to LPS. All above inflammation factors have been proved to be involved in the formation of AS. After comprehensive analysis of all results to discuss the structure-activity relationship, we summarized the conclusions at follow: compounds 1-7 could inhibit the expression of VEGF, CRP, JNK2, p38 and NO at different level, and we evaluated that flavonol aglycone have more significant anti-inflammation than it's glycoside, and the anti-AS activity of flavonols were stronger than flavanones and flavones, which means that 3-group might be the effective group. Eventually, we supposed the main anti-inflammatory mechanism of these compounds was to reduce the expression of CRP, inhibit the kinases activity of JNK2 and p38, and then the MAPK pathway was suppressed, which resulted in the decrease of NO synthesis, VEGF expression and endothelial adhesion factor expression. And eventually, the scar tissue and vascular stenosis formations were prevented. This conclusion suggested flavonoids have the potential of preventing AS formation. (C) 2017 Elsevier Ltd. All rights reserved.