Effects of 2,3,4 ',5-Tetrahydroxystilbene 2-O-beta-D-Glucoside on Vascular Endothelial Dysfunction in Atherogenic-Diet Rats
ABSTRACT 2,3,4',5-Tetrahydroxystilbene 2- O-beta- D-glucoside (TSG), an active component extracted from Polygonum multiflorum, has been found to have an anti-atherosclerotic effect. The aim of this study was to investigate whether the TSG could prevent the development of atherosclerosis through influencing endothelial function in atherogenic-diet rats and to explore the possible mechanisms. Vascular endothelial dysfunction was assessed using isolated aortic ring preparation, transmission electron microscopy of the aorta, and levels of nitrate/nitrite (NOx) in serum and aorta. Endothelial nitric oxide (NO) synthase (eNOS) and inducible NO synthase (iNOS) mRNA and protein expression were also measured. After 12 weeks treatment, TSG improved acetylcholine-induced endothelium-dependent relaxation, prevented intimal remodeling, inhibited the decreased NOx content in serum and aorta in atherogenic-diet rats. Furthermore, the observed decreased eNOS mRNA and protein expression and increased iNOS mRNA and protein expression in atherogenic-diet rats were attenuated by TSG treatment. These results suggest that TSG could restore vascular endothelial function, which may be related to its ability to prevent changes of eNOS and iNOS expression, leading to preservation of NO bioactivity.
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ABSTRACT: 1. 2,3,4′,5-Tetrahydroxystilbene-2-O-β-d-glucoside (TSG) has been shown to have an anti-atherosclerotic effect. Vascular smooth muscle cell (VSMC) proliferation contributes to the pathobiology of atherosclerosis. The aim of the present study was to investigate the effects of TSG on platelet-derived growth factor (PDGF)-BB-induced VSMC proliferation and to explore the molecular mechanisms underlying the effects. 2. Cultured rat VSMC were pretreated with TSG (l–50 μmol/L) for 1 h, followed by exposure to PDGF-BB (10 ng/mL) for 24 h, after which cell proliferation and cell cycle stages were examined. The expression of protein cell cycle regulators, including retinoblastoma (Rb), cyclin D1/E, cyclin-dependent kinase (CDK) 2/4, CDK inhibitors p21 and p27 and proliferative cell nuclear antigen (PCNA), was examined. Activation of extracellular signal-regulated kinase (ERK) 1/2 was evaluated to elucidate the possible upstream mechanism by which TSG affects cell cycle regulators. 3. The results showed that TSG dose-dependently inhibited PDGF-BB-induced VSMC proliferation, possibly by blocking the progression of the cell cycle from the G1 to S phase. In addition, TSG significantly inhibited PDGF-BB-induced phosphorylation of Rb and the expression of cyclin D1, CDK4, cyclin E, CDK2 and PCNA. In addition, TSG suppressed PDGF-BB-induced downregulation of p27 and upregulation of p21, as well as PDGF-BB-induced activation of ERK1/2. 4. Together, the findings of the present study provide the first evidence that TSG can inhibit PDGF-BB-stimulated VSMC proliferation via cell cycle arrest in association with modulation of the expression of cell cycle regulators, which may be mediated, at least in part, by suppression of ERK1/2 activation.Clinical and Experimental Pharmacology and Physiology 02/2011; 38(5):307-13. DOI:10.1111/j.1440-1681.2011.05502.x · 2.41 Impact Factor
- Recent Advances in Theories and Practice of Chinese Medicine, 01/2012; , ISBN: 978-953-307-903-5
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ABSTRACT: Atherosclerosis (AS) is a systemic cardiovascular disease with complicated pathogenesis involving oxidative stress, endothelial dysfunction and chronic inflammation. Increasing lines of evidence have questioned the statins-dominated treatment for AS, including their dangerous side-effects such as the breakdown of muscle when taken in larger doses. A multifaceted approach that addresses all major risk factors or pathological targets may provide an ideal treatment for AS. Studies of the herbal remedies on the prevention and treatment of AS have received much attention in recent years. This review summarizes some important experimental findings regarding their mechanisms of action on AS. Using the pre-set PUBMED searching syntax and inclusion criteria, representative citations published in English concerning the experimental studies of 14 herbal materials were included. We found that many extracts and (or) single compounds from these herbal materials, such as Salvia miltiorrhiza, Curcuma longa, Rheum undulatum and Panax notoginseng, could regulate multiple key targets involved in the initiation and propagation of AS. Some important findings about the effects of herbal formulations on AS were also reviewed. Given the complicated nature of AS and the holistic, combinational approach of herbal remedies, we propose that mixed herbal preparations with multiple active ingredients may be preferable for the prevention and treatment of AS. Further rigorously designed pharmacological evaluation and multi-centred clinical trials are warranted.Phytotherapy Research 02/2012; 26(2):159-67. DOI:10.1002/ptr.3587 · 2.40 Impact Factor