Ginsenoside Re inhibits vascular neointimal hyperplasia in balloon-injured carotid arteries through activating the eNOS/NO/cGMP pathway in rats

Biomed Pharmacother. 2018 Oct:106:1091-1097. doi: 10.1016/j.biopha.2018.07.044. Epub 2018 Jul 17.

Abstract

Ginsenoside Re (GS-Re) is one of the main ingredients of ginseng, a widely known Chinese traditional medicine, and has a variety of beneficial effects, including vasorelaxation, antioxidative, anti-inflammatory, and anticancer properties. The aims of the present study were to observe the effect of GS-Re on balloon injury-induced neointimal hyperplasia in the arteries and to investigate the mechanisms underlying this effect. A rat vascular neointimal hyperplasia model was generated by rubbing the endothelium of the common carotid artery (CCA) with a balloon, and GS-Re (12.5, 25 or 50 mg/kg/d) were subsequently continuously administered to the rats by gavage for 14 days. After GS-Re treatment, the vessel lumen of injured vessels showed significant increases in the GS-Re 25.0 and 50.0 mg/kg/d (intermediate- and high-dose) groups according to H.E. staining. Additionally, a reduced percentage of proliferating cell nuclear antigen (PCNA)-positive cells and an increased number of SM α-actin-positive cells were detected, and the levels of NO, cyclic guanosine monophosphate (cGMP), and eNOS mRNA as well as the phos-eNOSser1177/eNOS protein ratio were obviously upregulated in the intermediate- and high-dose groups. Moreover, the promotive effects of GS-Re on NO and eNOS expression were blocked by L-NAME treatment to different degrees. These results suggested that GS-Re can suppress balloon injury-induced vascular neointimal hyperplasia by inhibiting VSMC proliferation, which is closely related to the activation of the eNOS/NO/cGMP pathway.

Keywords: Balloon injury; Endothelial nitric oxide synthase; Ginsenoside Re; Neointimal hyperplasia; Nitric oxide.

MeSH terms

  • Actins / metabolism
  • Angioplasty, Balloon / instrumentation*
  • Animals
  • Carotid Artery Injuries / enzymology
  • Carotid Artery Injuries / etiology
  • Carotid Artery Injuries / pathology
  • Carotid Artery Injuries / prevention & control*
  • Carotid Artery, Common / drug effects*
  • Carotid Artery, Common / enzymology
  • Carotid Artery, Common / pathology
  • Cell Proliferation / drug effects
  • Cyclic GMP / metabolism*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Ginsenosides / pharmacology*
  • Hyperplasia
  • Male
  • Neointima*
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type III / genetics
  • Nitric Oxide Synthase Type III / metabolism*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Rats, Sprague-Dawley
  • Second Messenger Systems / drug effects

Substances

  • Actins
  • Ginsenosides
  • Proliferating Cell Nuclear Antigen
  • smooth muscle actin, rat
  • Nitric Oxide
  • ginsenoside Re
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • Cyclic GMP