Puerarin protects pulmonary arteries from hypoxic injury through the BMPRII and PPARγ signaling pathways in endothelial cells

Pharmacol Rep. 2019 Oct;71(5):855-861. doi: 10.1016/j.pharep.2019.05.002. Epub 2019 May 7.

Abstract

Background: Recent evidence indicates that Puerarin has a protective effect on pulmonary arteries. In the present study, we aimed to investigate whether Puerarin could protect pulmonary arterial endothelial cells from hypoxic injury and determine its potential targets.

Methods: In our study, human pulmonary arterial endothelial cells (HPAECs) were injured by hypoxic (1% O2) incubation. Cell viability was detected by a cell counting kit (CCK8). The production of nitric oxide (NO) was detected by Griess reagent and endothelin-1 (ET-1) was detected by the ELISA method. Oxidative stress was measured by a fluorescence microscope via the fluorescent probe DCFH-DA. Western blotting was employed for studying the mechanism.

Results: The results show that Puerarin protects HPAECs from hypoxia-induced apoptosis and slightly improves cell viability. Puerarin increases NO and decreases ET-1 to prevent the imbalance between vasoactive substances induced by hypoxia in HPAECs. Puerarin also inhibits the oxidative stress induced by hypoxia. The results from the Western blot show that Puerarin activates the BMPRII/Smad and PPARγ/PI3K/Akt signaling pathways.

Conclusion: In conclusion, Puerarin protects HPAECs from hypoxic injury through the inhibition of oxidative stress and the activation of the BMPRII and PPARγ signaling pathways. This work provides insight into the development of Puerarin as a treatment for hypoxic pulmonary hypertension.

Keywords: BMPRII; Hypoxia; PPARγ; Puerarin; Pulmonary arterial endothelial cells.

MeSH terms

  • Apoptosis / drug effects
  • Bone Morphogenetic Protein Receptors, Type II / metabolism*
  • Cell Hypoxia / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Drugs, Chinese Herbal / pharmacology*
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Humans
  • Isoflavones / pharmacology*
  • Nitric Oxide / biosynthesis
  • Oxidative Stress / drug effects
  • PPAR gamma / metabolism*
  • Pulmonary Artery / cytology
  • Pulmonary Artery / drug effects*
  • Pulmonary Artery / metabolism
  • Signal Transduction

Substances

  • Drugs, Chinese Herbal
  • Isoflavones
  • PPAR gamma
  • Nitric Oxide
  • BMPR2 protein, human
  • Bone Morphogenetic Protein Receptors, Type II
  • puerarin