Morus alba extract modulates blood pressure homeostasis through eNOS signaling

Mol Nutr Food Res. 2016 Oct;60(10):2304-2311. doi: 10.1002/mnfr.201600233. Epub 2016 Jun 27.

Abstract

Scope: Morus alba is a promising phytomedicine cultivated in oriental countries that is extensively used to prevent and treat various cardiovascular problems. To date, despite its beneficial effects, the molecular mechanisms involved remain unclear. Thus, we investigate the vascular and haemodynamic effects of Morus alba extract in an experimental model focusing our attention on the molecular mechanisms involved.

Methods and results: Through vascular reactivity studies, we demonstrate that Morus alba extract evokes endothelial vasorelaxation through a nitric oxide-dependent pathway. Our molecular analysis highlights an increase in endothelial nitric oxide synthase (eNOS) phosphorylation. In vivo administration of Morus alba extract reduces blood pressure levels exclusively in wild-type mice, whereas it fails to evoke any haemodynamic effects in eNOS-deficient mice. Molecular analyses revealed that its beneficial action on vasculature is mediated by the activation of two important proteins that act as stress sensors and chaperones: PERK and heat shock protein 90. Finally, Morus alba extract exerts antihypertensive action in an experimental model of arterial hypertension.

Conclusion: Through its action on eNOS signaling, Morus alba extract could act as a food supplement for the regulation of cardiovascular system, mainly in clinical conditions characterized by eNOS dysfunction, such as arterial hypertension.

Keywords: Endothelium; Hypertension; Morus alba; Nitric oxide; Nutraceuticals.

MeSH terms

  • Administration, Oral
  • Animals
  • Blood Pressure / drug effects*
  • Chromatography, High Pressure Liquid
  • Dose-Response Relationship, Drug
  • HSP90 Heat-Shock Proteins / metabolism
  • Mesenteric Arteries / drug effects
  • Mesenteric Arteries / physiology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Morus / chemistry*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / genetics
  • Nitric Oxide Synthase Type III / metabolism*
  • Phosphorylation / drug effects
  • Plant Extracts / administration & dosage
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Rats, Inbred SHR
  • Signal Transduction / drug effects
  • Vasodilation / drug effects
  • eIF-2 Kinase / metabolism

Substances

  • HSP90 Heat-Shock Proteins
  • Plant Extracts
  • Nitric Oxide
  • Nitric Oxide Synthase Type III
  • Nos3 protein, mouse
  • PERK kinase
  • eIF-2 Kinase