Polydatin Restores Endothelium-Dependent Relaxation in Rat Aorta Rings Impaired by High Glucose: A Novel Insight into the PPARβ-NO Signaling Pathway

Wu, Yang; Xue, Lingui; Du, Weimin; Huang, Bo; Tang, Cen; Liu, Changqing; Qiu, Hongmei; Jiang, Qingsong

doi:10.1371/journal.pone.0126249

Cited by 21 publications

(30 citation statements)

References 21 publications

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“…Importantly, some of these effects result from a direct effect of HG on the vasculature. For example, Wu et al demonstrated that 55 mM HG directly impaired vasorelaxation [36]. Consistent with these earlier reports, we also found that aortas incubated with 30 mM HG, a concentration which mimics glucose levels more closely to that found in diabetic patients with poor glucose control, also displayed impaired endotheliumdependent vasorelaxation.…”

Section: Discussionsupporting

confidence: 92%

“…These findings provide novel insight into the antioxidant effects of EA in blood vessels under diabetic conditions. Exposure of vascular cells and blood vessels to glucose concentrations ranging from 4.2 g/L (23.1 mM) to 10 g/L (55 mM) for 24 hours resembles the diabetic milieu within cell culture systems [36,[68][69][70][71] and closely mimics a hyperglycemic environment in the vasculature of individuals with diabetes. Several studies have shown that endothelial dysfunction arises even after short-term hyperglycemic injury is inflicted.…”

Section: Discussionmentioning

confidence: 99%

“…Evidence shows that HG can directly impair vasorelaxation [6,36]. To determine whether long-term stimulation with HG impairs endothelium-dependent vasorelaxation, we performed cumulative concentration curves to ACh in intact aortic rings incubated with 30 mM HG for 24 hours.…”

Section: Effect Of Ea On Hg-induced Impaired Vasorelaxationmentioning

confidence: 99%

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Ellagic Acid Reduces High Glucose-Induced Vascular Oxidative Stress Through ERK1/2/NOX4 Signaling Pathway

Rozentsvit

Vinokur

Samuel

et al. 2017

Cell Physiol Biochem

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Background/Aims: Elevated production of reactive oxygen species (ROS) is linked to endothelial dysfunction and is one of the key contributors to the pathogenesis of diabetic vascular complications. Emerging evidence has indicated that ellagic acid (EA), a polyphenol found in fruits and nuts, possesses numerous biological activities including radical scavenging. However, whether EA exerts a vasculo-protective effect via antioxidant mechanisms in blood vessels exposed to diabetic conditions remains unknown. Accordingly, the goal of this current study was to determine whether EA decreases vascular ROS production and thus ameliorates endothelial dysfunction in the diabetic milieu. Methods: Intact rat aortas and human aortic endothelial cells (HAEC) were stimulated with 30mM high glucose (HG) with and without EA co-treatment. Endothelium-dependent vasodilation was measured using a wire myograph. Gene and protein expression of non-phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 4 (NOX4) were detected using RT-PCR and western blotting, respectively. Oxidative stress was determined by measuring ROS levels using dihydroethidium (DHE) staining. Results: Intact aortas exposed to HG condition displayed exacerbated ROS production and impairment of endothelium-dependent vasodilation, characterizing endothelial dysfunction. These effects were markedly reduced with EA treatment. HG enhanced ROS production in HAEC, paralleled by increased ERK1/2 activation and NOX4 expression. EA treatment blunted the increase of ROS generation, ERK1/2 activation and decreased NOX4. Conclusions: EA significantly decreases endothelial ROS levels and ameliorates the impairment of vascular relaxation induced by HG. Our results suggest that EA exerts a vasculo-protective effect under diabetic conditions via an antioxidant effect that involves inhibition of ERK1/2 and downregulation of NOX4.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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Ellagic Acid Reduces High Glucose-Induced Vascular Oxidative Stress Through ERK1/2/NOX4 Signaling Pathway

Rozentsvit

Vinokur

Samuel

et al. 2017

Cell Physiol Biochem

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“…RNA was extracted from the thoracic aorta samples using TRIzol solution (Thermo Fisher Scientific, Inc., Waltham, MA, USA), quantified by ultraviolet spectrometric detection using BioPhotometer Plus (Eppendorf, Hamburg, Germany) according to the manufacturer's protocol (24) and reverse transcribed into complementary DNA using a PrimeScript RT Reagent kit (Takara Biotechnology, Co., Ltd., Dalian, China), according to the manufacturer's protocol. qPCR analysis was performed to analyze the mRNA expression of eNOS, iNOS and nNOS using the SYBR Premix Ex Taq II kit (Takara Biotechnology, Co., Ltd.) with a program of 30 sec at 95˚C, followed by 40 cycles of 15 sec at 95˚C and 1 min at 60˚C.…”

Section: Rna Extraction and Reverse Transcriptase-polymerase Chain Rementioning

confidence: 99%

“…According to the method for NOS activity established by Wu et al (24), the total (t)NOS [constitutive (c)NOS and iNOS] and iNOS activities were assayed in accordance with the NOS typed assay kit (cat. no.…”

Section: Determination Of Nos Activity and No Contentmentioning

confidence: 99%

Effects of aerobic exercise on the expressions and activities of nitric oxide synthases in the blood vessel endothelium in prediabetes mellitus

Wang

Zhang

et al. 2019

Exp Ther Med

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Previous studies by our group have indicated that exercise intervention can ameliorate endothelial dysfunction, which is an early pathophysiological change of prediabetes mellitus. The present study aimed to test the hypothesis that nitric oxide synthases (NOSs), which are expressed in blood vessel endothelium, contribute to the mitigation of vascular endothelium-dependent dysfunction by aerobic exercise in prediabetes mellitus. A prediabetic rat model was established by feeding the rats an additional high-energy diet, and was confirmed by testing blood glucose levels, the area-under-the-curve for the blood glucose tests (P<0.05) and the changes to the histological morphology of the thoracic aorta. Further examination identified that NOS expression changed significantly between the control and prediabetes groups, indicating endothelial dysfunction in the prediabetic rats. Following aerobic exercise, a significant increase in NOS, endothelial (eNOS) mRNA and protein expression (P<0.05), and a significant decrease in NOS, inducible (iNOS) mRNA and protein expression (P<0.05) was identified in the prediabetic rats compared with the control group. No significant change in nitric oxide synthase, brain expression was observed in the prediabetic rat group compared with the control group. Notably, there was also a significant increase and decrease in eNOS and iNOS activity, respectively, in the prediabetes group compared with the control group (P<0.05). Furthermore, nitric oxide (NO) concentration in the vascular endothelium was detected, which revealed a significant increase in NO concentration in the prediabetic rats following aerobic exercise compared with the control (P<0.05). The present study provided results that demonstrated that aerobic exercise ameliorated the vascular endothelium-dependent dysfunction through the NOS/NO signaling pathway, which is primarily regulated by NOS expression and activity, in prediabetes mellitus. The current study provided the theoretical basis for the use of exercise intervention to prevent diabetes mellitus during the early stage.

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Old dog, new tricks: Polydatin as a multitarget agent for current diseases

Jiang

et al. 2021

Phytotherapy Research

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Polydatin (PD) is a natural single‐crystal product that is primarily extracted from the traditional plant Polygonum cuspidatum Sieb. et Zucc. Early research showed that PD exhibited a variety of biological activities. PD has attracted increasing research interest since 2014, but no review comprehensively summarized the new findings. A great gap between its biological activities and drug development remains. It is necessary to summarize new findings on the pharmacological effects of PD on current diseases. We propose that PD will most likely be used in cardiac and cerebral ischaemia/reperfusion‐related diseases and atherosclerosis in the future. The present work classified these new findings according to diseases and summarized the main effects of PD via specific mechanisms of action. In summary, we found that PD played a therapeutic role in a variety of diseases, primarily via five mechanisms: antioxidative effects, antiinflammatory effects, regulation of autophagy and apoptosis, maintenance of mitochondrial function, and lipid regulation.

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Polydatin Restores Endothelium-Dependent Relaxation in Rat Aorta Rings Impaired by High Glucose: A Novel Insight into the PPARβ-NO Signaling Pathway

Cited by 21 publications

References 21 publications

Ellagic Acid Reduces High Glucose-Induced Vascular Oxidative Stress Through ERK1/2/NOX4 Signaling Pathway

Ellagic Acid Reduces High Glucose-Induced Vascular Oxidative Stress Through ERK1/2/NOX4 Signaling Pathway

Effects of aerobic exercise on the expressions and activities of nitric oxide synthases in the blood vessel endothelium in prediabetes mellitus

Old dog, new tricks: Polydatin as a multitarget agent for current diseases

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