1. Academic Validation
  2. Stachydrine Mediates Rapid Vascular Relaxation: Activation of Endothelial Nitric Oxide Synthase Involving AMP-Activated Protein Kinase and Akt Phosphorylation in Vascular Endothelial Cells

Stachydrine Mediates Rapid Vascular Relaxation: Activation of Endothelial Nitric Oxide Synthase Involving AMP-Activated Protein Kinase and Akt Phosphorylation in Vascular Endothelial Cells

  • J Agric Food Chem. 2019 Sep 4;67(35):9805-9811. doi: 10.1021/acs.jafc.9b03501.
Xinya Xie 1 Chunmiao Yang 1 Qi Cui Wen Ma 1 Jia Liu 1 Qinyu Yao 1 Zihui Zhang 1 Lei Xiao 1 Nanping Wang
Affiliations

Affiliation

  • 1 Cardiovascular Research Center, School of Basic Medical Sciences , Xi'an Jiaotong University , Xi'an 710061 , China.
Abstract

Stachydrine (STA) is a constituent of citrus fruits and Leonurus heterophyllus Sweet. In the present study, we established that STA caused acute endothelium-dependent relaxation. The vascular action of STA was mediated by nitric oxide (NO) via cyclic guanosine monophosphate. Mechanistically, STA activated AMP-activated protein kinase (AMPK), protein kinase B/Akt, and endothelial NO Synthase (eNOS) in vascular endothelial cells (ECs). AMPK inhibition by compound C blocked STA-induced Akt/eNOS phosphorylation, suggesting that AMPK is the upstream of Akt and eNOS. Inhibition of Akt by MK2206 blocked STA-stimulated eNOS phosphorylation without altering AMPK phosphorylation. Furthermore, we showed that STA activated AMPK via the induction of liver kinase B1 phosphorylation. These results indicated that STA can induce eNOS phosphorylation and vasorelaxation by regulating the interplay between AMPK and Akt pathways in ECs. These findings further highlighted the potential of STA as a nutritional factor in the beneficial effects of fruit intake in preventing the endothelial dysfunction-related metabolic cardiovascular diseases.

Keywords

endothelial nitric oxide synthase; endothelium-dependent relaxation; signal transduction; stachydrine.

Figures
Products