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: 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (THSG), a natural product purified from the Chinese medical herb Polygoni multiflori Radix, has been demonstrated to possess many pharmacological activities, including antioxidant, anti-inflammatory, hepatoprotective and antitumor properties. Ultra performance liquid chromatography– time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and high performance liquid chromatography-ultraviolet detection (HPLC-UV) methods were developed for the pharmacokinetics, bioavailability, absorption and metabolism studies of THSG in rats following a single intravenous or oral administration. The metabolites (M1 and M2) were identified in plasma by UPLC-Q-TOF/MS. The concentrations of the THSG in rat plasma, bile and urine or faeces samples were determined by HPLC-UV. The results show THSG was rapidly absorbed within 30 min in plasma. Absolute bioavailability of THSG was 40%. Total recovery of unchanged THSG within 24 h were low (0.041% in bile, 0.06% in faeces), whereas the amount of unchanged THSG excreted in the urine within 24 h was lower than LLOQ.Journal of Liquid Chromatography & Related Technologies 03/2013; 36(6):717–730. · 0.57 Impact Factor
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ABSTRACT: BACKGROUND AND PURPOSE: Many organs suffer from ischemic injuries that reduce the ability to generate sufficient energy, which is required for functional maintenance and repair. Erythropoietin (EPO) has the potential to ameliorate ischemic tissue by pleiotropic effects. The aim of this study was to investigate a small molecule EH-201 (2,3,5,4'-tetrahydroxystilbene-2-o-beta-d-glucoside, THSG) with a potent EPO induction effect in nonhaematopoietic cells and examine the compound's therapeutic potential in ischemic disorders. EXPERIMENTAL APPROACH: Mice kidney slices, primary hepatocytes, primary cardiomyocytes, and C2C12 myoblasts were exposed to the EH-201. The effects of treatment on EPO, haemoglobin expression, and mitochondrial biogenesis were analysed. In vivo, doxorubicin-induced cardiomyopathic mice were treated with EH-201. The mice were subjected to the endurance test, electrocardiography and echocardiography, and a histological examination of the isolated hearts was performed. EH-201 was also administered to cisplatin-induced nephropathic mice. KEY RESULTS: We demonstrated that EH-201 is a potent EPO-inducer and activates EPO-mediated mitochondrial function and haemoglobin expression in nonhaematopoietic cells. Using EPO and EPO receptor neutralising antibodies in mechanistic studies, we confirmed that EH-201 enhances EPO-EPOR autocrine activity. EH-201 robustly increased the endurance performance activity of healthy and cardiomyopathic mice during hypoxic stress, with induction of myocardial mitochondrial biogenesis and haemoglobin expression, as well as improved cardiac function. EH-201 also ameliorated anaemia and renal dysfunction in nephropathic mice. CONCLUSIONS AND IMPLICATIONS: The enhancement and recovery of cellular functions through the stimulation of mitochondrial activity and haemoglobin production in nonhaematopoietic cells by an inducer of endogenous EPO might serve as a potential therapeutic strategy for ischemic diseases.British Journal of Pharmacology 03/2013; · 5.07 Impact Factor
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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