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Journal of Pharmacology and Experimental Therapeutics

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Research ArticleCardiovascular

Astragaloside IV Stimulates Angiogenesis and Increases Hypoxia-Inducible Factor-1α Accumulation via Phosphatidylinositol 3-Kinase/Akt Pathway

Ling Zhang, Qian Liu, Lin Lu, Xiaoping Zhao, Xiumei Gao and Yi Wang
Journal of Pharmacology and Experimental Therapeutics August 2011, 338 (2) 485-491; DOI: https://doi.org/10.1124/jpet.111.180992
Ling Zhang
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Qian Liu
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Lin Lu
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Xiaoping Zhao
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Xiumei Gao
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Yi Wang
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Abstract

Astragaloside IV is the major active constituent of Astragalus membranaceus, which has been widely used for the treatment of cardiovascular diseases in China. The aim of this study was to determine the angiogenic effect of astragaloside IV and its underlying mechanism. We used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay, Western blotting, real-time polymerase chain reaction, and immunofluorescence to detect the effect of astragaloside IV on proliferation of human umbilical vein endothelial cells (HUVECs), the phospho-Akt protein level, hypoxia-inducible factor-1α (HIF-1α) accumulation, vascular endothelial growth factor mRNA expression, and applied cell migration, tube formation, and chick chorioallantoic membrane assays to study the angiogenic effect of astragaloside IV. Results indicate that astragaloside IV promoted cell proliferation and stimulated HIF-1α accumulation during hypoxia. Mechanism studies revealed that astragaloside IV did not affect the degradation of HIF-1α protein or the level of HIF-1α mRNA. In contrast, astragaloside IV apparently activated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which regulates HIF-1α protein synthesis. Moreover, astragaloside IV also stimulated cell migration, increased tube formation, and promoted angiogenesis in the chick chorioallantoic membrane assay. All angiogenic effects of astragaloside IV were reversed by the PI3K inhibitor. Taken together, our data collectively reveal that astragaloside IV is a novel regulator of HIF-1α and angiogenesis through the PI3K/Akt pathway in HUVECs that are exposed to hypoxia.

Footnotes

  • This work was supported by the National Natural Science Foundation of China [Grants 30830121, 30801461]; the National Key Scientific and Technological Project of China [Grant 2009ZX09311-002]; and the International S&T Cooperation Project of China [Grant 2009DFB30510].

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.111.180992.

  • ABBREVIATIONS:

    HIF-1α
    hypoxia-inducible factor-1α
    VEGF
    vascular endothelial growth factor
    HUVEC
    human umbilical vein endothelial cell
    PI3K
    phosphatidylinositol 3-kinase
    DMSO
    dimethyl sulfoxide
    M199
    medium 199
    FBS
    fetal bovine serum
    MTT
    3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide
    HC
    hypoxia control
    NC
    normal control
    PBS
    phosphate-buffered saline
    PCR
    polymerase chain reaction
    LY294002
    2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
    CAM
    chick chorioallantoic membrane
    MG132
    N-benzoyloxycarbonyl (Z)-Leu-Leu-leucinal.

  • Received February 25, 2011.
  • Accepted May 13, 2011.
  • Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 338 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 338, Issue 2
1 Aug 2011
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Research ArticleCardiovascular

Astragaloside IV Stimulates Angiogenesis and Increases Hypoxia-Inducible Factor-1α Accumulation via Phosphatidylinositol 3-Kinase/Akt Pathway

Ling Zhang, Qian Liu, Lin Lu, Xiaoping Zhao, Xiumei Gao and Yi Wang
Journal of Pharmacology and Experimental Therapeutics August 1, 2011, 338 (2) 485-491; DOI: https://doi.org/10.1124/jpet.111.180992

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Research ArticleCardiovascular

Astragaloside IV Stimulates Angiogenesis and Increases Hypoxia-Inducible Factor-1α Accumulation via Phosphatidylinositol 3-Kinase/Akt Pathway

Ling Zhang, Qian Liu, Lin Lu, Xiaoping Zhao, Xiumei Gao and Yi Wang
Journal of Pharmacology and Experimental Therapeutics August 1, 2011, 338 (2) 485-491; DOI: https://doi.org/10.1124/jpet.111.180992
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