notoginsenoside-fc and Diabetic-Angiopathies

Interventional therapies, such as percutaneous transluminal angioplasty and endovascular stent implantation, are used widely for the treatment of diabetic peripheral vascular complications. Reendothelialization is an essential process in vascular injury following interventional therapy, and hyperglycemia in diabetes mellitus (DM) plays an important role in damaging endothelial layer integrity, leading to the retardance of reendothelialization and excessive neointimal formation. Notoginsenoside Fc (Fc), a novel saponin isolated from

Topics: Animals; Autophagy; Cell Proliferation; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Endothelial Cells; Endothelium, Vascular; Ginsenosides; Male; Rats; Rats, Sprague-Dawley

Endothelial injury from high glucose (HG) plays a dominant role in atherosclerosis, diabetes-induced vasculopathy, and vascular remodeling. Notoginsenoside Fc (Fc), a novel saponin isolated from P. notoginseng, has been shown to exhibit properties that counteract platelet aggregation. However, the potential roles and molecular mechanisms of Fc in preventing cardiovascular injury have yet to be explored. In this study, we present novel data that show the ability of Fc to prevent early atherosclerosis of diabetic Sprague-Dawley (SD) rats in vivo and to attenuate endothelial cell injury in vitro. Our results indicate that Fc protects rat aortic endothelial cells (RAOECs) from HG-induced injury by inhibiting apoptosis and promoting proliferation as well as by reducing endothelial cell production of pro-inflammatory cytokines: TNF-α, IL-1β, IL-6, ICAM-1. Furthermore, the downregulation of peroxisome proliferator-activated receptor-γ (PPAR-γ) in HG-challenged endothelial cells was prevented by Fc. Inhibition of PPAR-γ abrogated the effects of Fc on HG-induced pro-inflammatory cytokine production in RAOECs. These results indicate that Fc has a preventative effect on HG-induced endothelial cell injury partly through a PPARγ-mediated pathway, suggesting that Fc might provide a potential new therapeutic option for the treatment of diabetic vascular complications.

Topics: Animals; Apoptosis; Blood Glucose; Cell Proliferation; Cells, Cultured; Cytokines; Cytoprotection; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Dose-Response Relationship, Drug; Endothelial Cells; Female; Ginsenosides; Inflammation Mediators; PPAR gamma; Rats, Sprague-Dawley; Signal Transduction; Time Factors; Up-Regulation