Ellagic Acid, the Active Compound of Phyllanthus urinaria, Exerts In Vivo Anti-Angiogenic Effect and Inhibits MMP-2 Activity

Abstract EN

This study aimed to assess the potential anti-angiogenic mechanism of Phyllanthus urinaria (P.

urinaria) and characterize the major compound in P.

urinaria that exerts anti-angiogenic effect.

The water extract of P.

urinaria and Ellagic Acid were used to evaluate the anti-angiogenic effect in chorioallantoic membrane (CAM) in chicken embryo and human vascular endothelial cells (HUVECs).

The matrix metalloproteinase-2 (MMP-2) activity was determined by gelatin zymography.

The mRNA expressions of MMP-2, MMP-14 and tissue inhibitor of metalloproteinase-2 (TIMP-2) were analyzed by reverse transcription polymerase chain reaction (RT-PCR).

Level of MMP-2 proteins in conditioned medium or cytosol was determined by western blot analysis.

We confirmed that P.

urinaria's in vivo anti-angiogenic effect was associated with a reduction in MMP-2 activity.

Ellagic acid, one of the major polyphenolic components as identified in P.

urinaria by high performance liquid chromatography mass spectrometry (HPLC/MS), exhibited the same anti-angiogenic effect in vivo.

Both P.

urinaria and Ellagic Acid inhibited MMP-2 activity in HUVECs with unchanged mRNA level.

The mRNA expression levels of MMP-14 and TIMP-2 were not altered either.

Results from comparing the change of MMP-2 protein levels in conditioned medium and cytosol of HUVECs after the P.

urinaria or Ellagic Acid treatment revealed an inhibitory effect on the secretion of MMP-2 protein.

This study concluded that Ellagic Acid is the active compound in P.

urinaria to exhibit anti-angiogenic activity and to inhibit the secretion of MMP-2 protein from HUVECs.