The Chinese medicine Fufang Zhenzhu Tiaozhi capsule protects against atherosclerosis by suppressing EndMT via modulating Akt1/β-catenin signaling pathway
作者:Hongtao Diao, Jiawen Cheng, Xueying Huang, Bingying Huang, Xiaoqi Shao, Jingjing Zhao, Dingming Lan, Qing Zhu, Meiling Yan, Yue Zhang, Xianglu Rong, Jiao Guo · 发表于:Journal of Ethnopharmacology · 年份:2022 · DOI:10.1016/j.jep.2022.115261 · 被引用次数:34 · 研究领域:Adipokines, Inflammation, and Metabolic Diseases、Zebrafish Biomedical Research Applications、Congenital heart defects research
ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Zhenzhu Tiaozhi (FTZ) is a traditional Chinese herbal prescription that has been used to treat dyslipidemia, nonalcoholic fatty liver disease, atherosclerosis, diabetes and its complications in the clinic for almost ten years. Endothelial-mesenchymal transition (EndMT) is the key driver of atherosclerosis. However, the effects of FTZ on endothelial dysfunction and EndMT remain unknown. AIM OF THE STUDY: To evaluate the therapeutic effects of FTZ against EndMT and the underlying mechanisms. MATERIALS AND METHODS: mice with a high-fat diet (HFD). The body weight, lipid levels, plaque area, lipid deposition and EndMT were evaluated using standard assays 12 weeks after intragastric administration of FTZ and simvastatin. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) to simulate EndMT in vitro. The degree of EndMT was assessed after treating the cells with FTZ or transfection with si-Akt1. The expression levels of genes involved in EndMT were quantified by real-time PCR or western blotting. RESULTS: FTZ ameliorated dyslipidemia and endothelial dysfunction in the atherosclerotic mice. In addition, FTZ reduced body weight and the total cholesterol, triglycerides and low-density lipoprotein levels, and increased that of high-density lipoproteins. FTZ also upregulated the expression of endothelial markers (CD31 and VE-cadherin) and decreased that of mesenchymal markers (ɑ-SMA and FSP1),...