Cytochalasin H, an Active Anti-angiogenic Constituent of the Ethanol Extract of Gleditsia sinensis Thorns

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  • Lee Jun
    KM-Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine
  • Yi Jin-Mu
    KM-Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine
  • Kim Haejin
    KM-Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine
  • Lee You Jin
    KM-Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine
  • Park Jong-Shik
    KM-Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine
  • Bang Ok-Sun
    KM-Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine
  • Kim No Soo
    KM-Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine

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  • Cytochalasin H, an Active Anti-angiogenic Constituent of the Ethanol Extract of <i>Gleditsia sinensis</i> Thorns

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Angiogenesis, the process of new vessel formation from the pre-existing blood vasculature, is critical for continuous tumor growth and is considered to be a validated antitumor target. The results of our previous study demonstrate the anti-angiogenic potential of an extract of Gleditsia sinensis thorns, which has been traditionally used in Korean medicine to remedy diverse diseases, including tumors. In the present study, we attempted to identify the active anti-angiogenic constituents of the ethanol extract of G. sinensis thorns (EEGS). By virtue of in vitro activity-guided fractionation using human umbilical vein endothelial cells (HUVEC) primary endothelial cells, chromatographic separation, and NMR spectral analyses, we isolated and identified the potent active constituent, cytochalasin H, a biologically active secondary metabolite of fungi. This unexpected active constituent may have originated from the endophytic fungi, Chaetomium globosum, which naturally populate G. sinensis, the identity of which was determined by analysis of fungal community. Cytochalasin H isolated from the EEGS showed in vitro anti-angiogenic activities such as suppressed cell growth and mobility in HUVEC, and inhibited the pro-angiogenic protein-induced formation of new blood vessels in vivo. The anti-angiogenic effect of cytochalasin H was in part due to reduced expression of pro-angiogenic factor, such as endothelin-1. This is the first report regarding the isolation and identification of cytochalasin H, as an active anti-angiogenic constituent of G. sinensis thorns.

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