Formononetin, J1 and J2 have different effects on endothelial cells via EWSAT1-TRAF6 and its downstream pathway
Formononetin, J1 and J2 have different effects on endothelial cells via EWSAT1-TRAF6 and its downstream pathway
复制标题
芒柄花素、J1和J2通过EWSAT1-TRAF6及其下游通路对内皮细胞产生不同的影响
DOI：
10.1111/jcmm.14797
复制
发表时间：
2020
影响因子：
5.3
通讯作者：
Huang Zhao Quan
中科院分区：
文献类型：
--
作者：
Li Xin;Huang Chen;Sui Cheng Liang;Liang Chun Mei;Qi Guang Ying;Ren Qian Yao;Chen Jian;Huang Zhao Quan
芒柄花素是一种天然的黄酮类化合物，主要存在于中草药如黄芪和红三叶草中。它被认为是一种典型的植物雌激素。在我们前期的实验中发现芒柄花素对内皮细胞（EC）具有双向调节作用：低浓度促进EC增殖，高浓度则具有抑制作用。为了找到特定的作用机制并提供更好的临床效果，我们进行了芒柄花素的结构转化，并从各种修饰的构建体中选择了芒柄花素修饰剂J1和J2的更好的药用特性。MTT法检测药物对人脐静脉内皮细胞（HUVEC）活性的影响。划痕实验和transwell实验证实了药物对HUVEC迁移和侵袭的影响。药物对卵巢切除大鼠的体内评价作用。应用基因芯片筛选HUVEC异常高表达的EWSAT 1的长链非编码RNA，应用PCR检测药物对其表达的影响。分析下游因素及其途径，并通过Western blot评估药物处理后蛋白水平的变化。综上所述，芒柄花素、J1和J2对EC的作用机制可能是通过EWSAT 1-TRAF 6及其下游途径。
Formononetin is a natural isoflavone compound found mainly in Chinese herbal medicines such as astragalus and red clover. It is considered to be a typical phytoestrogen. In our previous experiments, it was found that formononetin has a two-way regulatory effect on endothelial cells (ECs): low concentrations promote the proliferation of ECs and high concentrations have an inhibitory effect. To find a specific mechanism of action and provide a better clinical effect, we performed a structural transformation of formononetin and selected better medicinal properties for formononetin modifier J1 and J2 from a variety of modified constructs. The MTT assay measured the effects of drugs on human umbilical vein endothelial cell (HUVEC) activity. Scratch and transwell experiments validated the effects of the drugs on HUVEC migration and invasion. An in vivo assessment effect of the drugs on ovariwctomized rats. Long-chain non-coding RNA for EWSAT1, which is abnormally highly expressed in HUVEC, was screened by gene chip, and the effect of the drug on its expression was detected by PCR after the drug was applied. The downstream factors and their pathways were analysed, and the changes in the protein levels after drug treatment were evaluated by Western blot. In conclusion, the mechanism of action of formononetin, J1 and J2 on ECs may be through EWSAT1-TRAF6 and its downstream pathways.