Protective Effects Of Polydatin Research Articles

Protective effect of polydatin on radiation-induced injury of intestinal epithelial and endothelial cells.

This study aimed to examine the radioprotective effect of polydatin (PD) on crypt and endothelial cells of the small intestines of C57BL/6 mice that received abdominal irradiation (IR). Mice were treated with 6 MV X-ray (20 Gy) abdominal IR at a dose rate of 200 cGy/min. Thirty minutes before or after IR, mice were intraperitoneally injected with PD. The rate of survival of the mice at 30 days after IR was determined. The duodenum (upper small intestine), jejunum (middle small intestine), and ileum (lower small intestine) were collected and subjected to hematoxylin and eosin staining. Tissue sample sections were analyzed through light microscopy, and the lengths of at least 20 intestinal villi were measured in each group; the average number of crypts was obtained from 10 intestinal samples in each group. Microvessel density was assessed using CD31-positive (brown) vascular endothelial cells/cell clusters. FHs74Int cell proliferation was measured using the CCK-8 assay. PD administration (25 mg/kg) before IR was the most effective in prolonging the survival of C57BL/6 mice. PD reduced radiation-induced injury of intestinal villi, prevented loss of crypts, increased intestinal crypt growth, protected against IR-induced intestinal injury, and enhanced the proliferative potential and reduced the apoptosis of FHs74Int cells after IR. Moreover, PD increased small intestinal MVD and reduced the apoptosis of intestinal microvascular endothelial cells in mice after IR. Therefore, PD was found to be able to protect the two types of cells from radiation damage and to thus alleviate radiation-induced injury of small intestine.

Polydatin protects against ovalbumin-induced bronchial asthma in rats; involvement of urocortin and surfactant-D expression

Context: Prevalence of bronchial asthma massively increases worldwide, while the frequent therapies are still not sufficient. Polydatin, a naturally occurring glycoside, was known as to have anti-inflammatory and anti-oxidant effects.Objective: The current study aimed to investigate the possible protective effect of polydatin against experimental bronchial asthma in rats.Material and methods: Bronchial asthma was induced by ovalbumin (OVA) sensitization and challenge. Rats were randomly allocated into five groups; Group I (normal control group); Group II (asthma control group) received OVA; Group III (reference standard treatment group) received dexamethasone (1 mg/kg/day); Group IV (treatment group) received polydatin (200/mg/kg); and Group V (polydatin control group). The inflammatory biomarkers interleukin-4 (IL-4), IL-5, IL-13, tumor necrosis factor-alpha, interferon-gamma and absolute eosinophil count in bronchoalveolar lavage fluid (BALF), as well as serum immunoglobulin E were assessed, coupled with the oxido-nitrative stress biomarkers malondialdehyde and glutathione reduced levels and superoxide dismutase activity in the lung tissue, besides inducible nitric oxide synthase level in BALF. Western blot analysis of surfactant-D and immunohistochemical assay of urocortin (UCN) expression in the lung was performed.Results: Polydatin significantly reduced the inflammatory mediators and restored the normal values of oxidative and nitrosative stress biomarkers. It also significantly reduced the expression of surfactant-D and UCN as compared to asthma control. The histopathological study strongly augmented the biochemical results.Discussion and conclusions: Polydatin may be a promising protective agent against experimentally induced bronchial asthma. Modulation of SP-D and UCN expressions seems to mediate such protective effects.

Protective effects of polydatin and grape seed extract in rats exposed to cadmium

The current study aimed to investigate the protective role of polydatin (PD) and grape seed extracts (GSEs) against the effects of cadmium chlorine (CD) application in the rats. Forty-nine adult Wistar albino male rats were used in the study. Rats were assigned into control (saline), CD (5 mg/kg CdCI2), PD (120 mg/kg PD), GSE (120 mg/kg GSE), CD + PD (5 mg/kg CdCI2 + 120 mg/kg PD), CD + GSE (5 mg/kg CdCI2 + 120 mg GSE), and CD + PD + GSE (5 mg/kg CdCI2+120 mg/kg PD +120 mg/kg GSE) treatments (n = 7 per group). The treatments were administered orally for four weeks. CD accumulation was observed in all tissues studied except for the brain tissue. PD and GSE inhibited CD accumulation in erythrocytes and tissues at varying levels. The liver, kidney, brain, and testes showed extensive degenerative histopathological changes in CD group. Liver total oxidant status (TOS) in the CD group increased significantly compared to the control. TOS of kidney, brain, and testis suggested that PD and GSE did not show a strong antioxidant effect in these tissues. Malondialdehyde (MDA) levels in blood and liver raised significantly in CD-treated rats compared to controls. PD, GSE, and their combinations increased antioxidant potential in all tissues and decreased MDA levels in blood plasma and liver. Overall, the protective effects of PD were more effective than GSE. Results suggested that although the initiation of histopathological changes was present in all tissues, the initiating factor was not the oxidative stress in the tissues studied except for the liver and blood.

Polydatin protects against carbon tetrachloride-induced liver fibrosis in mice

Reactive oxygen species (ROS) play a key role in chronic liver injury and fibrosis. Polydatin, a glucoside of resveratrol, has been shown to possess anti-oxidative bioactivity. It has been demonstrated that resveratrol has many therapeutic effects on liver disorders including liver fibrosis. Recent study showed that polydatin prevented acute liver injury after carbon tetrachloride (CCl4) induction. However, the protective effects of polydatin on chronic liver injury and fibrosis has not been understood. Thus, we aimed to determine the roles of polydatin in chronic liver injury and fibrosis. Mice were induced by CCl4 for 6 weeks to develop chronic liver injury and fibrosis. Mice were treated with polydatin for 3 and 6 weeks, respectively. After 6 week injection of CCl4, the levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were markedly increased. The hepatic expression of α-SMA, collagen deposition and macrophage filtration were also increased. Furthermore, hepatic 4-HNE production and NOX4 expression were also increased in CCl4-induced mice. In contrast, polydatin ameliorated impaired liver function and histology. Moreover, polydatin attenuated liver fibrosis and inflammation in mice induced by CCl4. Additionally, polydatin suppressed hepatic 4-HNE production and NOX4 expression. In conclusion, polydatin ameliorate chronic liver injury and fibrosis through inhibition of oxidative stress and inflammation.

Polydatin Protects Rat Liver against Ethanol-Induced Injury: Involvement of CYP2E1/ROS/Nrf2 and TLR4/NF-κB p65 Pathway.

Excessive alcohol consumption leads to serious liver injury, associating with oxidative stress and inflammatory response. Previous study has demonstrated that polydatin (PD) exerted antioxidant and anti-inflammatory effects and attenuated ethanol-induced liver damage, but the research remained insufficient. Hence, this experiment aimed to evaluate the hepatoprotective effect and potential mechanisms of PD on ethanol-induced hepatotoxicity. Our results showed that PD pretreatment dramatically decreased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in the serum, suppressed the malonaldehyde (MDA) and triglyceride (TG) content and the production of reactive oxygen species (ROS), and enhanced the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), andalcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH), paralleled by an improvement of histopathology alterations. The protective effect of PD against oxidative stress was probably associated with downregulation of cytochrome P450 2E1 (CYP2E1) and upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its target gene haem oxygenase-1 (HO-1). Moreover, PD inhibited the release of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) via downregulating toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) p65. To conclude, PD pretreatment protects against ethanol-induced liver injury via suppressing oxidative stress and inflammation.

Polydatin Prevents Methylglyoxal-Induced Apoptosis through Reducing Oxidative Stress and Improving Mitochondrial Function in Human Umbilical Vein Endothelial Cells.

Methylglyoxal (MGO), an active metabolite of glucose, has been reported to induce vascular cell apoptosis in diabetic complication. Polydatin (PD), a small natural compound from Polygonum cuspidatum, has a number of biological functions, such as antioxidative, anti-inflammatory, and nephroprotective properties. However, the protective effects of PD on MGO-induced apoptosis in endothelial cells remain to be elucidated. In this study, human umbilical vein endothelial cells (HUVECs) were used to explore the effects of PD on MGO-induced cell apoptosis and the possible mechanism involved. HUVECs were pretreated with PD for 2 h, followed by stimulation with MGO. Then cell apoptosis, reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) impairment, mitochondrial morphology alterations, and Akt phosphorylation were assessed. The results demonstrated that PD significantly prevented MGO-induced HUVEC apoptosis. PD pretreatment also significantly inhibited MGO-induced ROS production, MMP impairment, mitochondrial morphology changes, and Akt dephosphorylation. These results and the experiments involving N-acetyl cysteine (antioxidant), Cyclosporin A (mitochondrial protector), and LY294002 (Akt inhibitor) suggest that PD prevents MGO-induced HUVEC apoptosis, at least in part, through inhibiting oxidative stress, maintaining mitochondrial function, and activating Akt pathway. All of these data indicate the potential application of PD for the treatment of diabetic vascular complication.

Microdevice for the investigation of high-glucose induced lifespan and the protective effect of polydatin in C. elegans

Caenorhabditis elegans (C. elegans) has been widely used as a model organism for biomedical research due to its sufficient homology with human at molecular or genomic level. In this work, we describe a microfluidic device not only to investigate the response of C. elegans including lifespan and oxidative stress, but also to evaluate the protective effect of polydatin induced by high-glucose condition. It was found that the mean lifespan of worms was significantly reduced and the oxidative stress protein GST-4 was increased in worms that are subjected to high glucose. However, a certain dose of polydatin could weaken the increased oxidative stress induced by high-glucose and extend the lifespan, indicating the protective effect of polydatin against the toxic of high-glucose. The established approach is simple to operate, easy for realtime imaging and multiparatemer evaluations in parallel, providing a potential platform for drug evaluation/screening in a high throughput format at single animal resolution.

Protective effects of polydatin on lipopolysaccharide-induced acute lung injury through TLR4-MyD88-NF-κB pathway

The purpose of this study was to investigate the protective effect of PD against lipopolysaccharide (LPS)-induced acute lung injury (ALI) and explore its potential mechanism. In vivo, PD and dexamethasone were intraperitoneally administered 1h before LPS stimulation. Then, mice were sacrificed at 6h post-LPS stimulation. Neutrophil number, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF) were determined, as well as lung wet to dry ratio (W/D) and polymorphonuclear (MPO) activity. The protein expressions of Toll like receptor 4 (TLR4), myeloid differentiating factor 88 (MyD88), IL-1R-associated kinases 1 (IRAK1), IRAK4, inhibitor of nuclear factor kappa-B kinase (IKK)α, p-IKKα, IKKβ, p-IKKβ, inhibitor of NF-κB (IκBα), p-IκBα and NF-κB in lung tissues were assessed. Besides, we detected the IL-6, IL-1β, IL-8, TNF-α levels and TLR4, MyD88, NF-κB protein expressions in LPS-induced BEAS-2B cells. Consequently, PD significantly inhibited the levels of W/D, MPO, neutrophils number, TNF-α, IL-6, IL-1β and reversed TLR4-MyD88-NF-κB signaling pathway in lung tissues. In vitro assays, PD effectively negatively mediated the inflammatory cytokines and ameliorated the high expressions of TLR4, MyD88, NF-κB caused by LPS simulation in Human bronchial epithelial BEAS-2B cells. This study indicated that PD played a protective role in LPS-induced ALI and BEAS-2B cells. The results supported further study of PD as potential candidate for acute lung injury.

Ameliorative effect of polydatin on oxidative stress-mediated testicular damage by chronic arsenic exposure in rats.

Arsenic causes lipid peroxidation leading to alterations in antioxidant status in organisms. In this study, the reproductive effects of chronic exposure to arsenic and the protective effects of polydatin (PD) were evaluated in 35 Wistar male rats, which were divided equally into five groups. The control group received a normal diet and tap water, arsenic (100mgl(-1) , approximately 1/50 of oral LD50 ) was given via drinking water to experimental groups except control group, and PD was orally given to the other groups at dose of 50, 100 and 200mgkg(-1) for 60days. Arsenic administration decreased sperm motility, glutathione level, superoxide dismutase and catalase activities in testicular tissue of rats. In contrast, malondialdehyde level and DNA damage were found to be high levels in arsenic-treated group. Histopathologically, it was observed that decreased sperm concentration and degeneration of Sertoli cells in testicular tissue. PD administration, partially 200mgkg(-1) , reversed arsenic-induced lipid peroxidation, DNA damage, antioxidant enzyme activity and cell integrity in testis of rats. These results demonstrate that PD decreases arsenic-induced lipid peroxidation, enhances the antioxidant defence mechanism and regenerates tissue damage in testis of rats.

Inhibitory effect of polydatin on expression of toll-like receptor 4 in ischemia-reperfusion injured NRK-52E cells

Polydatin is a monocrystaline compound isolated from Polygonum cuspidatum Sieb. et Zucc. (Polygonaceae) with biological properties, such as anti-inflammation, anti-oxidative and nephroprotective effects. Increasing number of studies have demonstrated the protective effect of polydatin on renal ischemia reperfusion injury. However, the possible mechanisms of this protection are not fully elucidated. This study aimed to investigate the effect of polydatin on ischemia-reperfusion induced expression of toll-like receptor4 (TLR4) in rat renal tubular epithelia cells (NRK-52E), and analyze the mechanism of polydatin on TLR4 signal pathway. The cultured NRK-52E cells were incubated in three gas incubators for a period of 6 h at hypoxia and 24h at reoxygenation to simulate the ischemia-reperfusion injury in vitro. TLR4 mRNA level was analyzed by real-time-PCR, and the protein expression of TLR4 and NF-κB by Western blotting, while TNF-α and IL-1β proteins expressions were detected by ELISA. Polydatin downregulated I/R induced mRNA and protein expressions of TLR4, and decreased the protein expression of NF-κB, TNF-α and IL-1β. The TLR4 blocker partially antagonized the effect of I/R on NF-κB signaling, and such inhibitory effect was markedly enhanced by polydatin. In the present study, polydatin protects NRK-52E cells from I/R injury possibly by relieving the inflammatory response through regulation of TLR4/NF-κB signaling pathway.

Protective effect of polydatin, a natural precursor of resveratrol, against cisplatin-induced toxicity in rats

The aim of the present study was to evaluate the possible protective effect of polydatin (PD) on cisplatin (Cis) induced oxidative stress in rats. Totally, thirty male Wistar albino rats were fed standard rodent diet and divided into 5 equal groups: the control group (vehicle treated) was treated with physiological saline for ten days both orally and intraperitoneally (i.p.), the second group was orally treated with physiological saline and 7mg/kg single i.p. injection of Cis on the seventh day, and third, fourth, and fifth groups were treated orally PD at 25, 50, and 100mg/kg/day, respectively for 10days starting seven days before Cis injection and 7mg/kg single i.p. Cis was injected on the seventh day. Cis resulted in significant increase malondialdehyde levels and decreased glutathione levels. In addition, Cis treatment decreased superoxide dismutase and catalase activities in erythrocyte and tissues. Also, Cis treatment caused to increase DNA damage and affected serum biochemical parameters whereas slightly decreased AchE activity. However, treatment of PD resulted in reversal of Cis-induced oxidative stress, lipid peroxidation, and activities of antioxidant enzymes. In conclusion, PD has protective effect in rats against Cis-induced oxidative stress, enhances antioxidant defence mechanism, and regenerates their tissues.

Protective effect of polydatin against burn-induced lung injury in rats.

Polydatin (PD) has anti-inflammatory and anti-apoptotic effects in ischemic-reperfusion injury. Moreover, inflammatory responses and apoptosis play a role in the development of burn-induced lung injuries. Based on these findings, in this study we investigated the hypothesis that PD can ameliorate lung injury induced by extensive burns via reduction of inflammation and apoptosis. Rats were subjected to 30% total body surface area burn injury followed by resuscitation. The treatment group received 45 mg/kg PD, and the burn group received the same amount of normal saline solution. No burn injury was inflicted in the sham group. Microvascular permeability, interstitial edema, neutrophil recruitment, and histopathological changes were detected by measuring Evans blue concentration, wet-to-dry lung weight ratio (W/D), myeloperoxidase (MPO) activity, and hematoxylin and eosin staining, respectively. To investigate the mechanism of action of PD, enzyme-linked immunosorbent assay, cell counting, terminal deoxyribonucleotidyl transferase-mediated deoxyuridine 5-triphosphate-digoxigenin nick end labeling (TUNEL) staining, fluorometric assay, and Western blot were used for assessing levels of inflammatory cytokines (tumor necrosis factor alpha, interleukin [IL]-1β, and IL-6), total number of cells, and concentration of polymorphonuclear leukocytes (PMNs) in bronchoalveolar lavage fluid (BALF), the number of apoptotic cells, caspase-3 activity, and apoptosis-related proteins including Bax and Bcl-xl, respectively. Burn-injury rats exhibited significant lung injury characterized by the deterioration of histopathological characteristics, pulmonary microvascular hyperpermeability, and a high W/D, which were attenuated by PD (P = .007 for permeability, P = .004 for W/D). PD inhibited the burn-induced inflammatory response, as evidenced by the down-regulation of lung MPO activity (P = .008), total number of cells, PMN concentration in BALF, and the local and systemic levels of the pro-inflammatory cytokines examined. Moreover, PD treatment dramatically prevented burn-induced pulmonary cell apoptosis in lungs, as reflected by the decrease in the number of TUNEL-positive cells (P = .002) and changes in Bax, Bcl-xl, and caspase-3 activity (P = .03). PD ameliorates burn-induced lung injury via its anti-inflammatory and anti-apoptotic effects, and PD treatment may therefore serve as a potential therapeutic target for the treatment of critical burn injuries.

Protective Effects of Polydatin on Septic Lung Injury in Mice via Upregulation of HO-1

The present study was carried out to investigate the effects and mechanisms of polydatin (PD) in septic mice. The model of cecal ligation and puncture (CLP-)induced sepsis was employed. Pretreatment of mice with PD (15, 45, and 100 mg/kg) dose-dependently reduced sepsis-induced mortality and lung injury, as indicated by alleviated lung pathological changes and infiltration of proteins and leukocytes. In addition, PD inhibited CLP-induced serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production, lung cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase isoform (iNOS) protein expressions and NF-κB activation. Notably, PD upregulated the expression and activity of heme oxygenase (HO-)1 in lung tissue of septic mice. Further, the protective effects of PD on sepsis were abrogated by ZnPP IX, a specific HO-1 inhibitor. These findings indicated that PD might be an effective antisepsis drug.

Protective Effects of Polydatin from Polygonum cuspidatum against Carbon Tetrachloride-Induced Liver Injury in Mice

Polydatin is one of main compounds in Polygonum cuspidatum, a plant with both medicinal and nutritional value. The possible hepatoprotective effects of polydatin on acute liver injury mice induced by carbon tetrachloride (CCl4) and the mechanisms involved were investigated. Intraperitoneal injection of CCl4 (50 µl/kg) resulted in a significant increase in the levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and hepatic malondialdehyde (MDA), also a marked enhancement in the expression of hepatic tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and nuclearfactor-kappa B (NF-κB). On the other hand, decreased glutathione (GSH) content and activities of glutathione transferase (GST), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were observed following CCl4 exposure. Nevertheless, all of these phenotypes were evidently reversed by preadministration of polydatin for 5 continuous days. The mRNA and protein expression levels of hepatic growth factor-beta1 (TGF-β1) were enhanced further by polydatin. These results suggest that polydatin protects mice against CCl4-induced liver injury through antioxidant stress and antiinflammatory effects. Polydatin may be an effective hepatoprotective agent and a promising candidate for the treatment of oxidative stress- and inflammation-related diseases.

Polydatin alleviates non-alcoholic fatty liver disease in rats by inhibiting the expression of TNF-α and SREBP-1c

The pathophysiology of non-alcoholic fatty liver disease remains incompletely elucidated, and available treatments are not entirely satisfactory. Polydatin, a stilbenoid compound derived from the rhizome of Polygonum cuspidatum, has been recognised to possess hepatoprotective and anti-inflammatory activities. The purpose of the present study was to determine whether polydatin has a protective effect against hepatic steatosis induced by a high-fat diet (HFD) and to elucidate its underlying molecular mechanisms in rats. Male Sprague-Dawley rats were randomly divided into four groups, including normal control, HFD model and polydatin-treated groups with polydatin levels of 30 and 90 mg/kg. Following the experimental period, plasma total cholesterol (TC), triglyceride (TG) and hepatic lipid concentrations were determined. To identify a possible mechanism, we examined the changes in liver tumor necrosis factor-α (TNF-α), lipid peroxidation levels and sterol-regulatory element binding protein (SREBP-1c) mRNA and its target genes. Both 30 and 90 mg/kg polydatin treatment alleviated hepatic steatosis and reduced plasma and liver TG, TC and free fatty acid (FFA) concentration significantly in HFD rats. In addition, TNF-α, and malondialdehyde and 4-hexanonenal levels were markedly suppressed by polydatin in the liver of HFD-fed rats. Polydatin also decreased the gene expression of SREBP-1c and its target genes involved in lipogenesis, including fatty acid synthase (FAS) and stearoly-CoA desaturase 1 (SCD1) in HFD-fed rats. These results suggest that the protective effects of polydatin against HFD-induced hepatic steatosis may be partly associated with reduced liver TNF-α expression, lipid peroxidation level and SREBP-1c-mediated lipogenesis.