Rosmarinic acid exerts an antagonistic effect on vascular calcification by regulating the Nrf2 signalling pathway

Free Radic Res. 2019 Feb;53(2):187-197. doi: 10.1080/10715762.2018.1558447. Epub 2019 Mar 13.


Vascular calcification (VC) is a process in which calcium phosphate crystals deposit within the intima and middle membrane of the vascular wall. Rosmarinic acid (RA) is a common phenolic compound. It possesses antioxidation, anti-inflammatory, antimicrobial effects. Our experiment aims to investigate the role and molecular mechanism of RA in VC. Rats were fed high-fat feed and injected with vitamin D3 to establish a VC model. β-Glyerophosphate (β GP) was selected to stimulate rat aortic smooth muscle cells (VSMCs) in order to establish the cell calcification model. Kits were used to detect the antioxidant index and calcification index. RA significantly reduced the levels of ALP, MDA, Ca, and P but increased SOD levels. Quantitative real-time polymerase chain reaction (RT-qPCR) and western blot analysis were used to detect various antioxidant-related genes and calcified genes on an mRNA and protein level. The results showed that nuclear factor red cell-2 related factors (Nrf2), haem oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase (NQO1), and osteoprotegerin (OPG) were up regulated by RA at both the mRNA and protein levels, but kelch-like ECH-associated protein 1 (Keap1), nuclear factor kappa B(NF-κB), cadherin associated protein (β-catenin) and osteogenic transcription factor (Runx2) expression at both the mRNA and protein levels was significantly inhibited. Microscopic examination showed that RA significantly decreased the content of calcified nodules and the production of reactive oxygen species (ROS). When Nrf2 is disturbed, the role of RA is significantly blocked. Our results showed that RA can improve VC by regulating the Nrf2 pathway.

Keywords: Nrf2; oxidative stress; rosmarinic acid (RA); vascular calcification (VC).

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Cinnamates / pharmacology
  • Cinnamates / therapeutic use*
  • Depsides / pharmacology
  • Depsides / therapeutic use*
  • Humans
  • Male
  • Mice
  • NF-E2-Related Factor 2 / metabolism*
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Vascular Calcification / drug therapy*
  • Vascular Calcification / pathology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cinnamates
  • Depsides
  • NF-E2-Related Factor 2
  • rosmarinic acid