2. Academic Validation
  3. The Chinese medicine Fufang Zhenzhu Tiaozhi capsule protects against atherosclerosis by suppressing EndMT via modulating Akt1/β-catenin signaling pathway

The Chinese medicine Fufang Zhenzhu Tiaozhi capsule protects against atherosclerosis by suppressing EndMT via modulating Akt1/β-catenin signaling pathway

  • J Ethnopharmacol. 2022 Jul 15;293:115261. doi: 10.1016/j.jep.2022.115261.
Hongtao Diao 1,  Jiawen Cheng 2,  Xueying Huang 3,  Bingying Huang 4,  Xiaoqi Shao 5,  Jingjing Zhao 6,  Dingming Lan 7,  Qing Zhu 8,  Meiling Yan 9,  Yue Zhang 10,  Xianglu Rong 11,  Jiao Guo 12
Affiliations

Affiliations

  • 1 Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, 510006, China. Electronic address: [email protected].
  • 2 Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, 510006, China. Electronic address: [email protected].
  • 3 Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, 510006, China. Electronic address: [email protected].
  • 4 Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, 510006, China. Electronic address: [email protected].
  • 5 Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, 510006, China. Electronic address: [email protected].
  • 6 Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, 510006, China. Electronic address: [email protected].
  • 7 Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, 510006, China. Electronic address: [email protected].
  • 8 Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou, 510006, China. Electronic address: [email protected].
  • 9 Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, 510006, China. Electronic address: [email protected].
  • 10 Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, 510006, China. Electronic address: [email protected].
  • 11 Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou, 510006, China. Electronic address: [email protected].
  • 12 Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou, 510006, China. Electronic address: [email protected].
PMID: 35447198 DOI: 10.1016/j.jep.2022.115261
Abstract

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: An in vivo model of atherosclerosis was established by feeding ApoE-/- 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), indicating that it inhibits EndMT. Knocking down Akt1 exacerbated EndMT and reversed the therapeutic effect of FTZ.

Conclusion: FTZ delayed atherosclerosis by inhibiting EndMT via the Akt1/β-catenin pathway.

Keywords

Akt1; Atherosclerosis; EndMT; Fufang-Zhenzhu-Tiaozhi (FTZ); β-catenin.

Figures
Products
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    Target
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  • HY-120697
    99.73%, Wnt/β-catenin Signaling Inhibitor