, Volume 14, Issue 2, pp 187–197 | Cite as

The natural compound n-butylidenephthalide derived from the volatile oil of Radix Angelica sinensis inhibits angiogenesis in vitro and in vivo

  • Ju-Ching Yeh
  • Tereza Cindrova-Davies
  • Mirella Belleri
  • Lucia Morbidelli
  • Nigel Miller
  • Chin-Wen Chantal Cho
  • Kelvin Chan
  • Yi-Tao Wang
  • Guo-An Luo
  • Marina Ziche
  • Marco Presta
  • David Stephen Charnock-Jones
  • Tai-Ping Fan
Original Paper


Radix Angelica sinensis is a Chinese medicinal herb that has been used extensively in the East for the treatment of cardiovascular diseases (CVDs). Angiogenesis plays an important role in the pathogenesis of CVDs. We hypothesized that Radix A. sinensis may contain angiogenesis modulators. In the current study, we investigated the effects of a volatile oil of Radix A. sinensis (VOAS) and n-butylidenephthalide (BP), one of the bioactive components in VOAS, on angiogenesis in vitro and in vivo. The results suggested that VOAS exerted anti-angiogenic effects by inhibiting human umbilical vein endothelial cell proliferation, migration and capillary-like tube formation on Matrigel. BP was also shown to be anti-angiogenic and its mechanisms were through inhibition of cell cycle progression and induction of apoptosis. Western blotting analysis indicated that the anti-angiogenic actions of BP were associated with the activation of p38 and ERK 1/2 but not SAPK/JNK and Akt signaling pathways. Further investigations showed that BP inhibited endothelial sprouting in an ex vivo mouse aortic ring model and was a potent inhibitor of the development of zebrafish subintestinal vessels in vivo. Our data using the volatile oil contrast with previous findings, which showed an aqueous extract of Radix A. sinensis was pro-angiogenic. This highlights the importance of identifying pro- and anti-angiogenic substances in Radix A. sinensis, not only for the development of novel angiogenesis modulators for the treatment of CVDs, but also to ensure the proper use of Radix A. sinensis as a nutraceutical.


Radix Angelica sinensis n-butylidenephthalide Angiogenesis 

Supplementary material

10456_2011_9202_MOESM1_ESM.doc (690 kb)
Supplementary material 1 (DOC 690 kb)


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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Ju-Ching Yeh
    • 1
    • 2
  • Tereza Cindrova-Davies
    • 3
  • Mirella Belleri
    • 4
  • Lucia Morbidelli
    • 5
  • Nigel Miller
    • 6
  • Chin-Wen Chantal Cho
    • 2
  • Kelvin Chan
    • 7
  • Yi-Tao Wang
    • 8
  • Guo-An Luo
    • 9
  • Marina Ziche
    • 5
  • Marco Presta
    • 4
  • David Stephen Charnock-Jones
    • 1
    • 10
  • Tai-Ping Fan
    • 2
  1. 1.Department of Obstetrics and GynecologyUniversity of Cambridge, The Rosie HospitalCambridgeUK
  2. 2.Angiogenesis and Chinese Medicine Laboratory, Department of PharmacologyUniversity of CambridgeCambridgeUK
  3. 3.Department of Physiology, Development and NeuroscienceUniversity of CambridgeCambridgeUK
  4. 4.Department of Biomedical Sciences and BiotechnologyUniversity of BresciaBresciaItaly
  5. 5.Department of Molecular BiologyUniversity of SienaSienaItaly
  6. 6.Department of PathologyUniversity of CambridgeCambridgeUK
  7. 7.Faculty of PharmacyUniversity of Sydney and College of Health and Science, University of Western SydneySydneyAustralia
  8. 8.Institute of Chinese Medical SciencesUniversity of MacauMacau SARChina
  9. 9.Department of ChemistryTsinghua UniversityBeijingChina
  10. 10.National Institute for Health ResearchCambridge Biomedical CentreCambridgeUK

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