Notoginsenoside R1 attenuates atherosclerotic lesions in ApoE deficient mouse model

PLoS One. 2014 Jun 16;9(6):e99849. doi: 10.1371/journal.pone.0099849. eCollection 2014.

Abstract

Aims: Atherosclerosis is the primary cause of cardiovascular diseases and stroke. The current study evaluated the interventional effects of a naturally occurring compound Notoginsenoside R1 (NR1) on atherosclerosis in ApoE-/- mice.

Methods and results: The atherosclerotic lesion was significantly alleviated by NR1 treatment and this attenuation was marked by reduction in lipid deposition, fibrosis and oxidative stress. Increased serum levels of GSH and SOD and decreased level of MDH were observed in NR1-treated ApoE-/- mice. NR1 treatment also significantly decreased the levels of CHO, TG, ox-LDL and increased the level of HDL. Additionally, the levels of inflammatory cytokines including IL-2, IL-6, TNF-α and γ-IFN were markedly reduced in NR1-treated ApoE-/- mice. Furthermore, significantly increased aortic expression of miR-26a, miR-21, miR-126a, miR-132, miR-146 and miR-155 and decreased expression of miR-20a and miR-92a were observed in the vehicle-treated ApoE-/- mice. While NR1 treatment led to a significant reduction in the expression of miR-21, miR-26a, miR-126 and increased expression of miR-20a.

Conclusion: Collectively, our results demonstrated for the first time the anti-atherosclerotic effects of NR1, which could be in part mediated through its multiple targeting effects on inflammation, oxidative stress, lipid metabolism and microRNA expression. These results therefore justify further evaluation of NR1 as a therapeutic agent treating atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / pathology
  • Apolipoproteins E / deficiency*
  • Apolipoproteins E / metabolism
  • Atherosclerosis / blood
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / genetics
  • Atherosclerosis / pathology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Gene Expression Regulation / drug effects
  • Ginsenosides / pharmacology
  • Ginsenosides / therapeutic use*
  • Inflammation Mediators / metabolism
  • Lipid Metabolism / drug effects
  • Lipids / blood
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Oxidative Stress / drug effects

Substances

  • Apolipoproteins E
  • Cytokines
  • Ginsenosides
  • Inflammation Mediators
  • Lipids
  • MicroRNAs
  • notoginsenoside R1

Grants and funding

This work was supported by the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning (YC and TZ), Program for Pu Jiang Scholar at Science and Technology Commission of Shanghai Municipality (11PJ1409000, 13PJ1407800, YC and TZ), Shu Guang Project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation (13SG42, YZ), National Natural Science Foundation of China (81273960) (TZ), Funding for Outstanding Junior Faculties at Shanghai Institutions of Higher Learning (ZZszy12048) (PW), Three-year Projects to Promote Traditional Chinese Medicine, Shanghai (NO. ZYSNXD-CC-ZDYJ050), and Key Disciplines of Clinical Integrative Medicine at the State Administration of Traditional Chinese Medicine of China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.