Ursolic acid suppresses leptin-induced cell proliferation in rat vascular smooth muscle cells

Can J Physiol Pharmacol. 2017 Jul;95(7):811-818. doi: 10.1139/cjpp-2016-0398. Epub 2017 Jan 29.

Abstract

Accumulating lines of evidence indicate that high leptin levels are associated with adverse cardiovascular health in obese individuals. Proatherogenic effects of leptin include endothelial cell activation and vascular smooth muscle cell proliferation and migration. Ursolic acid (UA) has been reported to exhibit multiple biological effects including antioxidant and anti-inflammatory properties. In this study, we investigated the effect of UA on leptin-induced biological responses in rat vascular smooth muscle cells (VSMCs). A-10 VSMCs were treated with leptin in the presence or absence of UA. Intracellular reactive oxygen species (ROS) was probed by 2',7'-dichlorofluorescein diacetate. The expression of extracellular signal-regulated kinase (ERK)1/2, phospho-(ERK)1/2, nuclear factor-kappa B (NF-κB) p65 and p50, and matrix metalloproteinase-2 (MMP2) was determined by Western blotting. Immunocytochemistry and confocal laser scanning microscopy were also used for the detection of NF-κB. The secretion of MMP2 was detected by gelatin zymography. UA exhibited antioxidant activities in vitro. In rat VSMCs, UA effectively inhibited cell growth and the activity of MMP2 induced by leptin. These suppressive effects appeared by decreasing the activation of (ERK)1/2, the nuclear expression and translocation of NF-κB, and the production of ROS. UA appeared to inhibit leptin-induced atherosclerosis, which may prevent the development of obesity-induced cardiovascular diseases.

Keywords: acide ursolique; atherosclerosis; athérosclérose; cellules musculaires lisses vasculaires; leptin; leptine; obesity; obésité; ursolic acid; vascular smooth muscle cells.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Gene Expression Regulation, Enzymologic / drug effects
  • Leptin / pharmacology*
  • Matrix Metalloproteinase 2 / metabolism
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Muscle, Smooth, Vascular / cytology*
  • NF-kappa B p50 Subunit / metabolism
  • Phosphoproteins / metabolism
  • Rats
  • Reactive Oxygen Species / metabolism
  • Transcription Factor RelA / metabolism
  • Triterpenes / pharmacology*

Substances

  • Antioxidants
  • Leptin
  • NF-kappa B p50 Subunit
  • Phosphoproteins
  • Reactive Oxygen Species
  • Transcription Factor RelA
  • Triterpenes
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Matrix Metalloproteinase 2
  • ursolic acid