Ferulic acid promotes endothelial cells proliferation through up-regulating cyclin D1 and VEGF

J Ethnopharmacol. 2011 Sep 2;137(2):992-7. doi: 10.1016/j.jep.2011.07.019. Epub 2011 Jul 18.


Ethnopharmacological relevance: Angelicae Sinensis is a well known and commonly used traditional Chinese herbal medicine with many therapeutic effects such as neuroprotection, the promotion of hematopoiesis and the treatment of tumors.

Aim of the study: Ferulic acid (FA) is the main active component in Angelicae Sinensis. Previous research has demonstrated that Angelicae Sinensis is able to induce angiogenesis in vivo. This study investigated the effects of FA on the proliferation of a human umbilical vein endothelial cell line (ECV304) with regard to the modulation of endothelial cells, which is a key step of angiogenesis.

Materials and methods: ECV304 cells were incubated with FA at different dosages (0.1 μg/mL, 1 μg/mL and 10 μg/mL). A series of assays was used to detect the effects of FA on: (i) cell proliferation; (ii) DNA synthesis; (iii) cell-cycle distribution; and (iv) mRNA expression of cyclin D1 and vascular endothelial growth factor (VEGF). These were assessed using the Cell Counting Kit-8 (CCK-8), bromodeoxyuridine-enzyme-linked immunosorbent assay (BrdU-ELISA), flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR), respectively.

Results and discussion: The results showed that FA at a range of concentrations from 0.1 μg/mL to 10 μg/mL could markedly improve cell proliferation and DNA synthesis in a dose-dependent manner. Flow cytometry showed a significant decrease in the percentage of cells in the G(0)/G(1) phase and a significant increase in the percentage of cells in the S phase. Furthermore, we found that FA enhanced cyclin D1 and VEGF mRNA expression in ECV304 cells.

Conclusion: FA was able to promote ECV304 cells proliferation in vitro. This effect might be observed through the modulation of cyclin D1 and VEGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Modulating Agents / pharmacology*
  • Cell Culture Techniques
  • Cell Cycle / drug effects
  • Cell Line
  • Cell Proliferation / drug effects*
  • Coumaric Acids / pharmacology*
  • Cyclin D1 / biosynthesis*
  • DNA / biosynthesis
  • Dose-Response Relationship, Drug
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Humans
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / biosynthesis*


  • Angiogenesis Modulating Agents
  • CCND1 protein, human
  • Coumaric Acids
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Cyclin D1
  • DNA
  • ferulic acid