Shen Wanli, Anwaier Gulinigaer, Cao Yini, Lian Guan, Chen Cong, Liu Shu, Tuerdi Nuerbiye, Qi Rong
School of Pharmacy, Shihezi University, Shihezi, China.
Institute of Cardiovascular Sciences, Peking University Health Science Center, Peking University, Beijing, China.
Front Physiol. 2019 Jul 2;10:825. doi: 10.3389/fphys.2019.00825. eCollection 2019.
Tilianin, a representative flavonoid ingredient of L., has been used to treat several diseases for centuries, including atherosclerosis (AS). However, pharmacological mechanisms underlying its biological functions remain elusive. In the present study, we investigated the anti-AS mechanisms of tilianin through establishing models using three types of cells that contributed to AS progression, including macrophage, vascular smooth muscle cells and human umbilical vein endothelial cells, which were proved to be involve in LPS/TNF-α/oxidized low density lipoprotein (ox-LDL)-induced inflammation and ox-LDL induced foam cell formation. Our results indicate that tilianin significantly suppressed LPS induced inflammatory responses on macrophage and remarkably inhibited TNF-α induced VSMCs proliferation and migration. Furthermore, the anti-inflammatory effect of tilianin on macrophages and VSMCs was proved to be mainly by downregulating TNF-α/NF-κB pathway. Moreover, our results demonstrate that tilianin significantly ameliorated ox-LDL induced macrophages oriented foam cells formation through repressing mRNA expression of SR-A1 and inducting the expression of genes related to cholesterol efflux including SRB-1 and ABCA1. However, tilianin had no effect on ox-LDL induced HUVECs injury.
田基黄苷是地锦草的一种代表性黄酮类成分，几个世纪以来一直被用于治疗多种疾病，包括动脉粥样硬化（AS）。然而，其生物学功能的药理学机制仍不清楚。在本研究中，我们通过使用三种促成AS进展的细胞建立模型，研究了田基黄苷的抗AS机制，这三种细胞包括巨噬细胞、血管平滑肌细胞和人脐静脉内皮细胞，已证明它们参与脂多糖/肿瘤坏死因子-α/氧化低密度脂蛋白（ox-LDL）诱导的炎症反应以及ox-LDL诱导的泡沫细胞形成。我们的结果表明，田基黄苷显著抑制脂多糖诱导的巨噬细胞炎症反应，并显著抑制肿瘤坏死因子-α诱导的血管平滑肌细胞增殖和迁移。此外，田基黄苷对巨噬细胞和血管平滑肌细胞的抗炎作用主要是通过下调肿瘤坏死因子-α/核因子-κB通路来实现的。而且，我们的结果表明，田基黄苷通过抑制清道夫受体-A1（SR-A1）的mRNA表达并诱导包括清道夫受体-B1（SRB-1）和三磷酸腺苷结合盒转运体A1（ABCA1）在内的与胆固醇流出相关基因的表达，显著改善ox-LDL诱导的巨噬细胞向泡沫细胞的转变。然而，田基黄苷对ox-LDL诱导的人脐静脉内皮细胞损伤没有影响。
