Effects of 2,3,4',5-tetrahydroxystilbene 2-O-beta-D-glucoside on vascular endothelial dysfunction in atherogenic-diet rats.

Department of Pharmacology, School of Medicine, Nantong University, Nantong, P. R. China.
Planta Medica (Impact Factor: 2.35). 05/2009; 75(11):1209-14. DOI: 10.1055/s-0029-1185540
Source: PubMed

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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 2,3,5,4'-Tetrahydroxystilbene-2-O-β-d-glucoside (TSG) has been shown to protect human umbilical vein endothelial cells (HUVECs) from lysophosphatidylcholine (LPC)-induced injury; however, the underlying molecular mechanism remains to be determined. The aim of this study was to investigate the protective mechanism of TSG against LPC-induced injury in HUVECs. We established a stable LPC-induced cell model by treating HUVECs with various concentrations of LPC and found 10.0 µg/mL of LPC to be optimal for inducing HUVECs injury. The effects of TSG on LPC-induced cell injury were assessed by cell counting kit-8, apoptosis assay, transmission electron microscope, and measurement of malondialdehyde (MDA), the antioxidant enzymes superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione peroxidase, and mitochondrial membrane potential. The mRNA and protein levels of caspase-3, Bax, Bcl-2, PARP-1, and cytochrome C were assayed by real-time reverse transcriptase-polymerase chain reaction and immunoblotting, respectively. TSG pretreatment was able to prevent LPC-induced HUVECs injury and restore cell viability in a concentration-dependent manner. LPC treated cells showed typical apoptotic morphological changes including cytoplasmic vacuolation, swollen mitochondria, and characteristic biochemical hallmarks of apoptosis including loss of mitochondrial membrane potential, activation of caspase-3, decrease of Bcl-2, increase of PARP-1, upregulation of Bax, and release of cytochrome C, all of which were apparently inhibited by TSG pretreatment. Treatment of HUVECs with LPC led to decrease of SOD and glutathione peroxidase in addition to rapid increase of MDA and ROS levels. Pretreatment with TSG restored SOD and glutathione peroxidase levels to that of normal levels, and significantly decreased ROS and MDA levels. Our data indicate that TSG inhibits apoptosis of HUVECs mediated by LPC through blocking the mitochondrial apoptotic pathway and suggest that the mechanisms underlying the protective effects of TSG are related to the activation of SOD and glutathione peroxidase, the clearance of intracellular ROS, and reduction of lipid peroxidation. © 2014 IUBMB Life, 2014.
    International Union of Biochemistry and Molecular Biology Life 11/2014; · 2.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the effect of 2,3,4',5-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), an active component extracted from the root of Polygonum multiflorum, on angiotensin II (Ang II)-induced proliferation of cultured rat vascular smooth muscle cells (VSMCs) and to identify the potential mechanism.
    Chinese journal of integrative medicine. 07/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Induction of pro-inflammatory factors is one of the characteristics of microglia activation and can be regulated by numerous active components of Chinese traditional herbs. Suppression of pro-inflammatory factors is beneficial to alleviate microglia-mediated cell injury. The present study aims to investigate the effect and possible mechanism of 2,3,4',5-tetrahydroxystilbene 2-O-beta-D-glucoside (TSG) on LPS-mediated induction of pro-inflammatory factors in microglia. Western blot, ELISA, and Hoechst 33258 were used to measure the protein expression, TNF-alpha/IL-6 content, and apoptotic nuclei, respectively. The mRNA level was measured by real time-PCR. Nitric oxide (NO) content, lactate dehydrogenase (LDH) content, and NF-kappaB binding activity were assayed by commercial kits. TSG reduced iNOS protein expression as well as TNF-alpha, IL-6, and NO content in LPS-stimulated BV-2 cells. TSG attenuated the increase in apoptotic nuclei, caspase-3 cleavage, and LDH content induced by BV-2 cell-derived conditioned medium in primary hippocampal neurons. Mechanistic studies showed that TSG reduced the mRNA level of iNOS, TNF-alpha, and IL-6. TSG failed to suppress IkappaB-alpha degradation, NF-kappaB phosphorylation and nuclear translocation, and ERK1/2, JNK, and p38 phosphorylation. TSG, however, markedly reduced the binding of NF-kappaB to its DNA element. Chromatin immunoprecipitation (ChIP) assays confirmed that TSG reduced NF-kappaB binding to the iNOS promoter. These findings were ascertained in primary microglia where the LPS-induced increase in iNOS expression, NO content, apoptotic nuclei, and NF-kappaB binding to its DNA element were diminished by TSG. These studies demonstrate that TSG attenuates LPS-mediated induction of pro-inflammatory factors in microglia through reducing the binding activity of NF-kappaB. This might help us to further understand the pharmacological role of TSG in inflammatory response in the central nervous system.
    Journal of Neuroinflammation 10/2013; 10(1):129. · 4.35 Impact Factor