Effects of a dammarane-type saponin,ginsenoside Rd,in nicotine-induced vascular endothelial injury |
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| Affiliation: | 1. Department of Medical Physiology, Hamamatsu University School of Medicine, Hamamatsu, Japan;2. Department of Cardiovascular Surgery, Keio University, Tokyo, Japan;3. Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, Japan;4. Department of Applied Biological Chemistry, Graduate School of Agricultural Science, Kinki University, Nara, Japan;5. Department of Organ & Tissue Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Japan;1. Department of Neurosurgery, The First Hospital of Jilin University, Changchun 130021, China;2. Department of Ophthalmology, The Third Hospital of Jilin University, China;1. Department of Pharmacy, Children''s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China;2. Department of Ophthalmology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China;3. Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing 400038, China;4. Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Third Military Medical University, Chongqing 400038, China;1. Key Laboratory of Yangtze River Water Environment, College of Environmental Science and Engineering, Tongji University, China;2. Division of Cardiology, TongRen Hospital, Shanghai Jiao Tong University School of Medicine, 1111 Xianxia Road, Shanghai 200336, China |
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| Abstract: | BackgroundPanax notoginseng (Burk.) F.H. Chen is a traditional medicinal plant widely used to prevent and treat cardiovascular diseases. Ginsenoside Rd (GRd) is a major bioactive component of P. notoginseng, but specific effects on cardiovascular disease-related pathogenic processes are rarely studied, especially vascular endothelial injury.PurposeThis study investigated the potential protective efficacy of GRd against nicotine-induced vascular endothelial cell injury, disruption of vascular nitric oxide (NO) signaling, aberrant endothelium–monocyte adhesion, platelet aggregation, and vasoconstriction.Study design/MethodsVascular endothelial injury and functional disruption were investigated in cultured human umbilical vein endothelial cells (HUVECs) by biochemical assays for nitric oxide (NO) and angiotensin II (Ang II), immunofluorescence (IF) and western blotting for expression analyses of apoptosis- related proteins, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), Ang II type receptor 1 (AGTR1), toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B (NF-κB). In addition, vascular protection by GRd was examined in nicotine-administered Sprague-Dawley (SD) rats by serum NO and Ang II assays, and by hematoxylin-eosin (HE) and immunostaining of aorta. We also examined effects of GRd on monocyte (THP-1 cells) adhesion assays, adenosine diphosphate (ADP)-induced platelet aggregation, and phenylephrine (PE)-induced vasoconstriction of isolated rat aortic rings.ResultsIn HUVECs, nicotine significantly suppressed NO production, enhanced Ang II production, downregulated eNOS expression, and upregulated expression levels of AGTR1, TLR4, MyD88, NF-κB, iNOS, Bax/Bcl-2 ratio, cleaved caspase-3, and cytochrome c (cyt c). All of these changes were significantly reversed by GRd. In rats, oral GRd reversed the reduction NO and enhanced Ang II production in serum induced by nicotine administration, and HE staining revealed protection of aortic endothelial cells. In addition, GRd reversed nicotine-mediated enhancement of HUVECs-monocyte adhesion, inhibited ADP-induced platelet aggregation and PE-induced vasoconstriction.ConclusionGRd may prevent nicotine-induced cardiovascular diseases by preserving normal vascular endothelial NO signaling, suppressing platelet aggregation and vasoconstriction, and by preventing endothelial cell–monocyte adhesion. |
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