Myricitrin inhibits vascular endothelial growth factor-induced angiogenesis of human umbilical vein endothelial cells and mice.

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
PMID: 34321178

Abstract

In the present study, the protective effects of myricitrin against vascular endothelial growth factor (VEGF)-induced angiogenesis of vascular endothelial cells were characterized. Cells were induced with 50 ng/mL VEGF in the presence or absence of various concentrations of myricitrin for 24 h. Myricitrin treatment significantly reduced cell proliferation by more than 50 %. Cells treated with myricitrin showed significantly increased caspase 3/7 activity and apoptosis in a dose-dependent manner. Treatment with 1, 10, or 100 μM myricitrin significantly reduced matrix metalloproteinase (MMP) activity by 23.3 %, 46.2 %, or 64.3 %, respectively. Myricitrin significantly reduced MMP1 and MMP2 mRNA expression. Similarly, treatment with 1, 10, or 100 μM myricitrin reduced MMP1 protein expression by 10.5 %, 31.6 %, or 52.6 %, respectively, and MMP2 protein expression by 10.9 %, 28.2 %, or 43.5 %, respectively. Cells treated with myricitrin showed significant inhibition of cell migration as well as capillary tube and sprouting formation. Myricitrin treatment significantly reduced the VEGF level. Immune-deficient nude mice bearing U251 xenograft tumors were used to investigate the antiangiogenic effects of myricitrin in vivo. The results demonstrated that myricitrin treatment in vivo significantly inhibited U251 cell xenograft tumor growth, as confirmed by the decreases in tumor volume and tumor weight. VEGF expression is a key proangiogenic factor. Myricitrin treatment significantly reduced mRNA and protein VEGF expression. Taken together, these results indicate that myricitrin is a potential inhibitor of VEGF-induced angiogenesis.

Authors

  • Zhipeng Hu
    Department of Vascular Surgery, The General Hospital of NingXia Medical University, Yinchuan, 750004, China.
  • Gang Zhao
    Department of Vascular Surgery, The General Hospital of NingXia Medical University, Yinchuan, 750004, China.
  • Wei Gou
    Department of Vascular Surgery, The General Hospital of NingXia Medical University, Yinchuan, 750004, China.
  • Hua Cheng
    Department of Medical Cardiology, The General Hospital of NingXia Medical University, Yinchuan, 750004, China. Electronic address: chenghzhp@126.com.

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