Leonurine Ameliorates Oxidative Stress and Insufficient Angiogenesis by Regulating the PI3K/Akt-eNOS Signaling Pathway in H2O2-Induced HUVECs

Oxid Med Cell Longev. 2021 Aug 3:2021:9919466. doi: 10.1155/2021/9919466. eCollection 2021.

Abstract

Thrombus is considered to be the pathological source of morbidity and mortality of cardiovascular disease and thrombotic complications, while oxidative stress is regarded as an important factor in vascular endothelial injury and thrombus formation. Therefore, antioxidative stress and maintaining the normal function of vascular endothelial cells are greatly significant in regulating vascular tension and maintaining a nonthrombotic environment. Leonurine (LEO) is a unique alkaloid isolated from Leonurus japonicus Houtt (a traditional Chinese medicine (TCM)), which has shown a good effect on promoting blood circulation and removing blood stasis. In this study, we explored the protective effect and action mechanism of LEO on human umbilical vein endothelial cells (HUVECs) after damage by hydrogen peroxide (H2O2). The protective effects of LEO on H2O2-induced HUVECs were determined by measuring the cell viability, cell migration, tube formation, and oxidative biomarkers. The underlying mechanism of antioxidation of LEO was investigated by RT-qPCR and western blotting. Our results showed that LEO treatment promoted cell viability; remarkably downregulated the intracellular generation of reactive oxygen species (ROS), malondialdehyde (MDA) production, and lactate dehydrogenase (LDH); and upregulated the nitric oxide (NO) and superoxide dismutase (SOD) activity in H2O2-induced HUVECs. At the same time, LEO treatment significantly promoted the phosphorylation level of angiogenic protein PI3K, Akt, and eNOS and the expression level of survival factor Bcl2 and decreased the expression level of death factor Bax and caspase3. In conclusion, our findings suggested that LEO can ameliorate the oxidative stress damage and insufficient angiogenesis of HUVECs induced by H2O2 through activating the PI3K/Akt-eNOS signaling pathway.

MeSH terms

  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Gallic Acid / analogs & derivatives*
  • Gallic Acid / pharmacology
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Malondialdehyde / metabolism
  • Medicine, Chinese Traditional
  • Neovascularization, Physiologic / drug effects
  • Nitric Oxide Synthase Type III / metabolism
  • Oxidative Stress / drug effects*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protective Agents / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects*
  • Superoxide Dismutase / metabolism

Substances

  • Protective Agents
  • Reactive Oxygen Species
  • leonurine
  • Malondialdehyde
  • Gallic Acid
  • Hydrogen Peroxide
  • Nitric Oxide Synthase Type III
  • Superoxide Dismutase
  • Proto-Oncogene Proteins c-akt