Isolariciresinol-9'-O-α-L-arabinofuranoside protects against hydrogen peroxide‑induced apoptosis of human umbilical vein endothelial cells via a PI3K/Akt/Bad‑dependent pathway

Mol Med Rep. 2018 Jan;17(1):488-494. doi: 10.3892/mmr.2017.7865. Epub 2017 Oct 25.

Abstract

Isolariciresinol-9'-O-α-L-arabinofuranoside (MWS‑19) isolated from Pinus massoniana Lamb. Fresh pine needles is the major ingredient of the Songling Xuemaikang capsule therapy used for hypertension. The present study aimed to investigate the effects and underlying mechanisms of MWS‑19 on hydrogen peroxide (H2O2)‑induced apoptosis in human umbilical vein endothelial cells (HUVECs). To investigate the effect of MWS‑19 on apoptosis in HUVECs, an oxidative stress‑induced apoptosis model was established in HUVECs using H2O2, and the present study performed Hoechst 33258 staining and a Cell Counting Kit‑8 (CCK‑8) assay. Furthermore, western blot analysis was also performed to investigate the underlying mechanism of the effects of MWS‑19 on the model. The results demonstrated that MWS‑19 reversed the effects of H2O2 on cell apoptosis at a concentration range of 15.6‑250 µg/ml, with dose‑dependent increases in cell growth. Hoechst staining indicated that 500 µM H2O2 induced HUVEC apoptosis, and MWS‑19 markedly protected HUVECs against apoptosis at 31.3, 62.5 and 125 µg/ml. Furthermore, the protein expression of phosphatidylinositol 3‑kinase (PI3K), phosphorylated‑Akt and Bcl‑2‑associated agonist of cell death (Bad) were increased, and reduced caspase‑3 activation was observed, following treatment with MWS‑19 in H2O2‑treated HUVECs. Additionally, the PI3K inhibitor wortmannin attenuated PI3K/Akt/Bad signaling induced by MWS‑19 treatment and neutralized the effect of MWS‑19 on the growth of HUVECs. In conclusion, the results of the present study indicate that MWS‑19 may protect against H2O2‑induced HUVEC apoptosis via the PI3K/Akt/Bad signaling pathway. MWS‑19 may serve an important role in the prevention of oxidative damage in vascular endothelial cells in hypertension patients.

MeSH terms

  • Apoptosis / drug effects*
  • Cell Survival / drug effects
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hydrogen Peroxide / pharmacology*
  • Phosphatidylinositol 3-Kinase / metabolism*
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects*
  • bcl-Associated Death Protein / metabolism*

Substances

  • Plant Extracts
  • bcl-Associated Death Protein
  • Hydrogen Peroxide
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt