Protective Effects Of Resveratrol Research Articles

Protective Effect of Resveratrol against Spleen Toxicity of Nicotine in Male Rat: Antioxidant and Histopathological Approaches

Nicotine is a tertiary amine, nicotine can freely cross the biological membranes of body organs. During smoking, nicotine is rapidly absorbed into the circulatory system, and blood concentration of nicotine rise quickly during and peak at the completion of cigarette smoking. Resveratrol is a compound is a member of a group of plant compounds called polyphenol which possess a free radical scavenger that increases the activity of several antioxidant enzymes. The study aimed to evaluate the influence of Resveratrol (Res) in rat with Nicotine (Nic) induced spleen toxicity, by evaluating the biochemical and histopathological changes. The experiment was carried out on four groups of male rats as follows; group 1 served as a control group, group 2 was treated with Nic (2.5 mg kg -1 ) in physiological saline, group 3 was received Res (20 mg Kg -1 ), group 4 was treated with combination of Nic (2.5 mg Kg -1 ) and Res (20 mg Kg -1 ). The results indicated that Nic increased lipid peroxidation, Myloperoxidase, xanthine oxidase, nitrite level, TOS level and decrease the antioxidant enzymes as well as decrease the thiol and G6PD levels . A serious congestion and stasis, correlated with congested red pulp and numerous secondary lymphoid follicles were observed. All the lymphatic nodules appeared smaller with multiple variable sized reactive germinal centers with peripherally located central arteriole in the animals treated with Nic. Nic/Res treatments improve all the oxidative damage and the histopathological changes. In the light of the present results, it is evident that Res was able to reduce the toxic effect of Nic in rat. Conclusion: Resveratrol had found to effect on antioxidant parameters of the spleen tissue. The present study indicates that a decrease in the antioxidant status is one of the main factors contributing to Nicotine toxicity to the spleen. Res treatment found to remove the continuously generated free radicals, to prevent the endogenous antioxidant enzymes decrease and act to prevent oxidative cell damage induced by Nic.

Protective Effect of Resveratrol on Mitochondria and Oxidative Stress induced by Cisplatin in HK‐2 Cells

Cisplatin is used in treating many cancers including testicular, ovarian and cervical cancer. Impaired renal function is a major side effect of cisplatin and occurs in 33% of patients treated with cisplatin. Resveratrol (RES) is a polyphenolic compound that possesses anticancer activity. Part of the mechanism for reducing cisplatin toxicity by RES may be mediated by maintaining mitochondrial function and reducing oxidative stress. The purpose of this study was to evaluate the effect of cisplatin on mitochondrial function in a human proximal tubular kidney cell line (HK‐2). Specifically the levels of ATP and ADP were measured following exposure to cisplatin in the presence of RES or DMSO (vehicle). HK‐2 cells were pretreated for 1 h with 0–15 uM RES (vehicle control 10% DMSO). Renal cells were subsequently exposed to cisplatin at a final concentration of 0–30 uM for 24 or 48 h. Viability was assessed using MTT release and cell count with an n=6/treatment group and repeated 3 separate times. Cells pretreated with 10 uM RES were protected from cisplatin cytotoxicity at 24 and 48 h. Cisplatin caused a concentration dependent decline in MTT viability after 24 h exposure to 0, 7.5 and 15 uM cisplatin. RES pretreatment for 1 h with 10 or 15 uM RES increased HK‐2 viability relative to cells exposed only to RES Vehicle (DMSO). Additional studies examined whether RES stimulated cell growth as part of the mechanism for cellular protection. RES did not increase cell number as part of its protective mechanism. ATP levels were diminished by cisplatin causing an increase in the relative balance of ADP/ATP. RES (5 and 7.5 uM) did not alter ATP or ADP/ATP ratios. Additional studies examined Caspase cleavage, protein carbonylation and 4‐hydroxynonenal adduction (4‐HNE) following cisplatin exposure of HK‐2 cells pretreated with DMSO or RES. Western analysis detected an increase in protein carbonylation with 24 h cisplatin exposure which was reversed by RES. In summary, RES protects HK‐2 cells from cisplatin cytotoxicity and preserves mitochondrial ATP levels.Support or Funding Information(Supported by NIH Grants INBRE 3P20RR016477‐09S4; 5P20RR016477 and 8P20GM103434 to the West Virginia IDeA Network for Biomedical Research Excellence).

Protective effects of resveratrol against hypoxanthine-xanthine oxidase-induced toxicity on human erythrocytes

An in vitro model of erythrocyte damage induced by hypoxanthine-xanthine oxidase (HX-XOD) was developed. The protective effects of resveratrol, a main component of red wine, were evaluated using this model. The results showed that resveratrol treatments maintained erythrocyte morphological and structural integrity, inhibited the formation of methaemoglobin, and suppressed the release of lactate dehydrogenase. Further investigation found that resveratrol attenuated the HX-XOD-induced reactive oxygen species generation, preserved erythrocyte antioxidant enzymes (SOD, CAT and GSH-Px) activities and increased GSH level. Also, resveratrol regulated the pyruvate kinase activity and pyruvate concentration, preserving the normal functioning of erythrocyte membrane ATPases (Na+/K+-ATPase and Ca2+/Mg2+-ATPase). This study established an ideal cellular model for the research of erythrocyte antioxidant system, and revealed the protective mechanisms of resveratrol on human erythrocyte. The results of this study provided novel evidences for further researches on the utilization of resveratrol as a protector on human erythrocyte.

Protective effects of resveratrol on aging-induced cognitive impairment in rats

Resveratrol, a polyphenol phytoalexine, has been shown to play a neuroprotective role in the neurodegenerative process in Alzheimer’s disease (AD) and improve memory function in dementia. However, the in vivo effect of resveratrol in normal aging models of learning and memory has not yet been evaluated. Therefore, the present neurobehavioral study was undertaken to evaluate the effect of resveratrol on cognitive impairment induced by aging in passive avoidance and Morris water maze (MWM) tests. Male Wistar albino rats were divided into four groups: young control (4month), young resveratrol (4month+RESV), old control (24month) and old resveratrol (24month+RESV). Resveratrol (50mg/kg/day) was given to the 4month+RESV and 24month+RESV groups orally for 12weeks. There was no significant difference between the groups for the first day of latency, while in aged rats, the second day of latency was significantly shortened compared to the young group in the passive avoidance test (p<0.05). Additionally, in the MWM test, the results showed a decrease in the time spent in the escape platform’s quadrant in the probe test in aged rats (p<0.05). The administration of resveratrol at 50mg/kg/day increased the retention scores in the passive avoidance test and the time spent in the escape platform’s quadrant in the MWM task (p<0.05). Furthermore resveratrol attenuated the protein levels of TNFα and IL1β in the 24-month group. These findings indicate that aging impairs emotional and spatial learning-memory and resveratrol reverses the effect of age-related learning and memory impairment. The results of this study suggest that resveratrol is effective in preventing cognitive deficit in aged rats by inhibiting the production of inflammatory cytokines.

Resveratrol attenuates inflammatory hyperalgesia by inhibiting glial activation in mice spinal cords.

The present study aimed to investigate the effect of resveratrol on inflammatory pain. Mice were injected intraperitoneally with lipopolysaccharide (LPS) for 5consecutive days to induce subacute systemic inflammation. Acetic acid‑induced writhing tests and tail‑flick tests were performed following the final LPS injection. Glial fibrillary acidic protein (GFAP; an astrocyte‑specific activation marker), ionized calcium binding adapter molecule1 (Iba‑1; a microglia‑specific activation marker) and sirtuin1 (SIRT1) protein expression levels were detected using immunohistochemistry analysis or western blotting. Following administration of LPS for 5days, the number of writhes increased and the tail‑flick latency decreased. Resveratrol (10 or 20mg/kg) partly inhibited LPS‑induced hyperalgesia and prevented the increase in tumor necrosis factor‑α and interleukin6 levels induced by LPS. LPS injection reduced the SIRT1 protein expression and increased the number of GFAP‑positive and Iba‑1‑positive cells in the spinal cord. Resveratrol increased the SIRT1 protein expression levels and decreased the number of GFAP‑positive and Iba‑1‑positive cells in LPS‑treated mice. The protective effect of resveratrol was partly blocked by a selective SIRT1 inhibitor, EX‑257. Results from the present study suggest that subacute treatment with LPS induced the activation of glial cells and hyperalgesia. Resveratrol was demonstrated to inhibit the activation of glial cells and attenuate inflammatory hyperalgesia in a SIRT1‑dependent manner.

Protective effect of resveratrol and quercetin on in vitro-induced diabetic mouse corpus cavernosum.

BackgroundHyperglycemia and increased levels of methylglyoxal (MGO) can trigger the development of vascular complications in diabetes. Resveratrol and quercetin are red wine polyphenols with known beneficial cardiovascular properties, including an antioxidant capacity. This study evaluated whether resveratrol and/or quercetin could prevent in vitro-induced diabetic changes in neurogenic and vascular relaxant responses of mouse arteries and corpora cavernosa.MethodsIsometric tension of isolated aorta, mesenteric arteries and corpora cavernosa was measured using organ bath systems. Diabetic conditions were mimicked in vitro by co-incubating the tissues for 2 h with high glucose (HG, 30 mM) and MGO (120 µM).ResultsThe presence of HG and MGO significantly blunted acetylcholine (Ach)-induced relaxations in corpora cavernosa and mesenteric arteries but not in aorta. Electrical field stimulated (EFS) responses of corpora cavernosa were also significantly inhibited by these diabetic conditions. In corpora cavernosa 2 h co-incubation with resveratrol (30 µM) or quercetin (30 µM) significantly attenuated HG and MGO-induced deficits in Ach- and EFS-responses.ConclusionsOur study demonstrates that in mouse arteries, HG and MGO rather affect endothelium derived hyperpolarizing factor-mediated than nitric oxide (NO)-mediated relaxations. In corpora cavernosa HG and MGO interfere with NO release. Resveratrol and quercetin protect mouse corpora cavernosa from diabetic-induced damage to NO-mediated relaxant responses. This might rely on their antioxidant capacity.

Protective effect of resveratrol against chronic intermittent hypoxia-induced spatial memory deficits, hippocampal oxidative DNA damage and increased p47Phox NADPH oxidase expression in young rats

Long-term intermittent hypoxia (IH) is a characteristic hallmark of obstructive sleep apnea (OSA) and causes most of the neurological aspects of OSA, such as spatial memory and learning deficits. These deficits are accompanied by an increase in oxidative stress and inflammation in brain areas involved in cognition, such as the hippocampus, particularly in children. Resveratrol is a natural polyphenolic compound with potent antioxidant, anti-inflammatory and neuroprotective properties. AimThe aim of this work is to study the possible protective effect of resveratrol against IH-induced neurobehavioral deficits and to investigate the possible mechanism of this protective effect in the young rat model of OSA. MethodsThe effect of resveratrol (5 and 10mg/kg, orally) on anxiety, spatial memory and learning deficits in young rats exposed to IH for 6 weeks and the corresponding biochemical changes were studied. ResultsResveratrol attenuated IH-induced anxiety and spatial memory deficits, as indicated by the elevated plus maze and Morris water maze tests, respectively, in a dose-dependent manner. In addition, resveratrol antagonized IH-induced increases in hippocampal glutamate, TBARS and 8-OHdG levels and p47Phox expression and decreases in GSH levels and GSH-Px activity in the hippocampus of IH-exposed young rats. ConclusionResveratrol ameliorates IH-induced anxiety and spatial learning deficits through multiple beneficial effects on hippocampal oxidative pathways that involve decreased expression of the p47Phox subunit of NADPH oxidase. Hence, the potential therapeutic role of resveratrol in OSA may be utilized in the near future and deserves further exploration.

Protective effect of resveratrol against pseudorabies virus-induced reproductive failure in a mouse model.

Resveratrol (RES), a natural polyphenol that is abundant in grapes, exerts anti-inflammatory, anti-oxidative, and antiviral bioactive effects. Protective effects of RES against pseudorabies virus (PrV)- induced reproductive failure were investigated in a mice model. Injection of PrV partially induced stillbirth and abortion, and caused poor growth of progeny. Treatment with RES attenuated the reproductive failure induced by the virus with recovery of the serum progesterone level. RES improved the growth performance of newborn mice. RES can attenuate the reproductive failure induced by PrV in mice.

Resveratrol Prevented Lipopolysaccharide-Induced Endothelial Dysfunction in Rat Thoracic Aorta Through Increased eNOS Expression

The cardiovascular benefits of Resveratrol (RVT) have been well established by previous experimental and clinical studies. The goal of this study was to test the effectiveness of RVT administration on the impaired endothelial function induced by lipopolysaccharide (LPS), and to elucidate the role of endothelial nitric oxide synthase (eNOS)/Sirtuin 1 (SIRT1) pathway. Animal experiment. Endotoxemia was induced by intraperitoneal injection of 10 mg/kg LPS, and the thoracic aorta was isolated six hours later. RVT was injected intraperitoneally 15 minutes before LPS administration. Six hours after LPS injection, potassium chloride (KCl), phenylephrine (Phe), acetylcholine (ACh), and sodium nitroprusside (SNP) were used to examine to vascular reactivity and endothelial function. eNOS, phospho-eNOS (p-eNOS) (Ser 1177), and SIRT1 expressions in thoracic aorta were evaluated by Western blot. LPS administration significantly inhibited the relaxation response induced by ACh, while the relaxation to SNP was not significantly altered. Phe- and KCl-induced contractile responses in the thoracic aorta significantly decreased in LPS-injected group. eNOS and p-eNOS expression decreased significantly in arteries obtained from LPS group rats. The impaired vasoreactivity as well as decreased expressions of eNOS, p-eNOS, and SIRT1 in vessels from LPS-injected rats were improved by RVT treatment. The endothelium-dependent vasodilatation of the thoracic aorta was significantly inhibited by LPS administration, and RVT treatment may improve vascular endothelial function. The protective effect of RVT might be associated with increased eNOS expression and activity.

Resveratrol Protects against TNF-α-Induced Injury in Human Umbilical Endothelial Cells through Promoting Sirtuin-1-Induced Repression of NF-KB and p38 MAPK.

Inflammation and reactive oxygen species (ROS) play important roles in the pathogenesis of atherosclerosis. Resveratrol has been shown to possess anti-inflammatory and antioxidative stress activities, but the underlying mechanisms are not fully understood. In the present study, we investigated the molecular basis associated with the protective effects of resveratrol on tumor necrosis factor-alpha (TNF-α)-induced injury in human umbilical endothelial cells (HUVECs) using a variety of approaches including a cell viability assay, reverse transcription and quantitative polymerase chain reaction, western blot, and immunofluorescence staining. We showed that TNF-α induced CD40 expression and ROS production in cultured HUVECs, which were attenuated by resveratrol treatment. Also, resveratrol increased the expression of sirtuin 1 (SIRT1); and repression of SIRT1 by small-interfering RNA (siRNA) and the SIRT1 inhibitor Ex527 reduced the inhibitory effects of resveratrol on CD40 expression and ROS generation. In addition, resveratrol downregulated the levels of p65 and phospho-p38 MAPK, but this inhibitory effect was attenuated by the suppression of SIRT1 activity. Moreover, the p38 MAPK inhibitor SD203580 and the nuclear factor (NF)-κB inhibitor pyrrolidine dithiocarbamate (PDTC) achieved similar repressive effects as resveratrol on TNF-α-induced ROS generation and CD40 expression. Thus, our study provides a mechanistic link between resveratrol and the activation of SIRT1, the latter of which is involved in resveratrol-mediated repression of the p38 MAPK/NF-κB pathway and ROS production in TNF-α-treated HUVECs.

The protective effect of resveratrol against cytotoxicity induced by mycotoxin, zearalenone

Zearalenone (ZEA), a non-steroidal estrogenic mycotoxin, is widely present in cereals and agricultural products. The literature reports suggest that oxidative damage seems to be a key determinant of ZEA-induced toxicity, and the protective effect of resveratrol (RSV), an antioxidant phenolic compound, on ZEA-induced cytotoxicity to HEK293 cells was investigated. The experimental results showed that ZEA decreased cell viability in a dose dependent manner with an IC50 value of 80 μM, and induced an increase in intracellular reactive oxygen species (ROS) in HEK293 cells. A remarkable elevation of MDA and decreased activity of manganese superoxide dismutase (MnSOD) were also observed. A decrease in mitochondrial membrane potential (MMP), cell cycle arrest at the G0/G1 phase, and increased cell apoptosis indicate a mitochondria-mediated apoptosis. RSV (2 μM) pretreatment not only recovered the activity of MnSOD, but also improved ZEA-induced cytotoxicity evidenced by increased MMP and cell viability, and decreased ROS. Furthermore, RSV pretreatment substantially upregulated the expression of the SIRT1 gene by 6.8 fold, reduced the acetylation level of the forkhead transcription factor FOXO3a, and decreased the expression ratio of Bax/Bcl-2. All these results demonstrated that RSV exhibited significant protective effects on ZEA-induced cell damage, and this effect may be attributed to the upregulation of SIRT1 and activation of FOXO3a-mediated pathways to enhance the resistance of cells to oxidative stress induced by ZEA exposure.

Resveratrol Enhances Autophagic Flux and Promotes Ox-LDL Degradation in HUVECs via Upregulation of SIRT1.

Oxidized low-density lipoprotein- (Ox-LDL-) induced autophagy dysfunction in human vascular endothelial cells contributes to the development of atherosclerosis (AS). Resveratrol (RSV) protects against Ox-LDL-induced endothelium injury. The objective of this study was to determine the mechanisms underlying Ox-LDL-induced autophagy dysfunction and RSV-mediated protection in human umbilical vein endothelial cells (HUVECs). The results showed that Ox-LDL suppressed the expression of sirtuin 1 (SIRT1) and increased LC3-II and sequestosome 1 (p62) protein levels without altering p62 mRNA levels in HUVECs. Pretreatment with bafilomycin A1 (BafA1) to inhibit lysosomal degradation abrogated the Ox-LDL-induced increase in LC3-II protein level. Ox-LDL increased colocalization of GFP and RFP puncta in mRFP-GFP-tandem fluorescent LC3- (tf-LC3-) transfected cells. Moreover, Ox-LDL decreased the expression of mature cathepsin D and attenuated cathepsin D activity. Pretreatment with RSV increased the expression of SIRT1 and LC3-II and increased p62 protein degradation. RSV induced RFP-LC3 aggregation more than GFP-LC3 aggregation. RSV restored lysosomal function and promoted Ox-LDL degradation in HUVECs. All the protective effects of RSV were blocked after SIRT1 was knocked down. These findings demonstrated that RSV upregulated the expression of SIRT1, restored lysosomal function, enhanced Ox-LDL-induced impaired autophagic flux, and promoted Ox-LDL degradation through the autophagy-lysosome degradation pathway in HUVECs.

The β-casein-resveratrol complex: Physicochemical characteristics and implications for enhanced nutrition

Food proteins have been widely used as carrier materials for the encapsulation and protection of bioactive molecules. Clarification the mechanism of protein-bioactive molecule interaction is important for the development protein-based carrier systems. Interaction of b-casein with resveratrol, a natural polyphenol, was studied using ultraviolet-visible absorption and fluorescence spectroscopy. It was found that the interaction shifted the protein fluorophores to a more hydrophilic environment but the polyphenol to a more hydrophobic environment. Formation of the complex with b-casein did not affect trans-cis isomerization of resveratrol or the total antioxidant activity of the protein-polyphenol system, as analyzed respectively using spectrophotometry and 2,2-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid assay. The protective effect of resveratrol against the photodecomposition of folic acid was not affected by binding to b-casein. The data obtained should provide insight into protein-polyphenol interaction mechanisms and aid the development of b-casein-based carrier systems for the delivery of bioactive molecules.

Resveratrol attenuated hydrogen peroxide-induced myocardial apoptosis by autophagic flux

BackgroundResveratrol is a Sirt-1-specific activator, which also exerts cardioprotective effects that regulate redox signalling during oxidative stress and autophagy during cardiovascular disease (CVD).ObjectiveThis study investigated the protective effects of resveratrol against hydrogen peroxide-induced damage in cardiomyocytes.DesignIn this article, hydrogen peroxide-induced autophagy and apoptosis in H9c2 cardiomyoblasts were studied at an increasing concentration from 0 to 100 µM.ResultsResveratrol pretreatment with concentrations of 10, 20, and 50 µM inhibits autophagic apoptosis by increasing p-Akt and Bcl-2 protein levels in H9c2 cells. Interestingly, resveratrol treatment activates the Beclin-1, LC3, p62, and the lysosome-associated protein LAMP2a within 24 h of administration.ConclusionsThese results suggest that resveratrol-regulated autophagy may play a role in degrading damaged organelles in H9c2 cells rather than causing apoptosis, and this may be a possible mechanism by which resveratrol protects the heart during CVD.

The protective effect of resveratrol on arterial remodeling in spontaneous hypertensive rats

Objective To observe the effect of resveratrol on arterial remodeling in spontaneous hypertensive rats. Methods Spontaneous hypertensive rats (SHRs, n=20) and Wistar-Kyoto rats (WKYs, n=10 ) were randomly assigned to three groups: control group, model group and resveratrol group. Systolic blood pressure (SBP) and pulse wave velocity (PWV) of the three groups was observed. Morphological observations were obtained by hematoxylin and eosin or victoria blue and picrosirius red. The content of nitric oxide (NO) and endothelin-1 (ET-1) were determined to assess the endothelial function. Oxidative stress was assessed by malondialdehyde (MDA), hydrogen peroxide (H2O2), and activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Results Compared with control group, SBP, PWV, wall thickness, wall-lumen ratio, vascular cross-sectional area (VCSA), luminal cross-sectional area (LCSA) and collagen-elastic ratio were increased, and the levels of NO, SOD, CAT in rat aortic tissues were decreased, while ET-1, MDA, H2O2 levels in rat aortic tissues were enhanced in model group at the end of 22 weeks. After the treatment of resveratrol, SBP had no significantly difference between model and resveratrol groups, while PWV, aortic wall thickness, wall-lumen ratio, VCSA, LCSA and collagen-elastic ratio were decreased in resveratrol group as compared with model group 〔(6681.1±2154.9) cm/s vs. (4283.1±946.1) cm/s, (234.7±51.8) μm vs. (123.4±21.5) μm, (10.3±2.3) % vs. (5.8±1.4) %, (6.4±0.4) mm2vs. (4.8±0.6) mm2, (4.1±0.1) mm2vs. (3.2±0.4) mm2, (1.1±0.3) vs. (0.4±0.2), P<0.05 or 0.01〕. Compared with model group, the expressions of NO, SOD, CAT in rat aortic tissues were increased and levels of ET-1, MDA, H2O2 in rat aortic tissues were decreased in resveratrol group after treatment of resveratrol (P<0.01 or P<0.05). Conclusions Resveratrol has an antioxidant effect, and it could attenuate arterial remodeling by improving oxidative stress. Key words: Resveratrol; Oxidative stress; Hypertension

Resveratrol Regulates Mitochondrial Biogenesis and Fission/Fusion to Attenuate Rotenone-Induced Neurotoxicity.

It has been confirmed that mitochondrial impairment may underlie both sporadic and familial Parkinson's disease (PD). Mitochondrial fission/fusion and biogenesis are key processes in regulating mitochondrial homeostasis. Therefore, we explored whether the protective effect of resveratrol in rotenone-induced neurotoxicity was associated with mitochondrial fission/fusion and biogenesis. The results showed that resveratrol could not only promote mitochondrial mass and DNA copy number but also improve mitochondrial homeostasis and neuron function in rats and PC12 cells damaged by rotenone. We also observed effects with alterations in proteins known to regulate mitochondrial fission/fusion and biogenesis in rotenone-induced neurotoxicity. Therefore, our findings suggest that resveratrol may prevent rotenone-induced neurotoxicity through regulating mitochondrial fission/fusion and biogenesis.

Metformin and Resveratrol Inhibited High Glucose-Induced Metabolic Memory of Endothelial Senescence through SIRT1/p300/p53/p21 Pathway

Endothelial senescence plays crucial roles in diabetic vascular complication. Recent evidence indicated that transient hyperglycaemia could potentiate persistent diabetic vascular complications, a phenomenon known as “metabolic memory.” Although SIRT1 has been demonstrated to mediate high glucose-induced endothelial senescence, whether and how “metabolic memory” would affect endothelial senescence through SIRT1 signaling remains largely unknown. In this study, we investigated the involvement of SIRT1 axis as well as the protective effects of resveratrol (RSV) and metformin (MET), two potent SIRT1 activators, during the occurrence of “metabolic memory” of cellular senescence (senescent “memory”). Human umbilical vascular endothelial cells (HUVECs) were cultured in either normal glucose (NG)/high glucose (HG) media for 6 days, or 3 days of HG followed by 3 days of NG (HN), with or without RSV or MET treatment. It was shown that HN incubation triggered persistent downregulation of deacetylase SIRT1 and upregulation of acetyltransferase p300, leading to sustained hyperacetylation (at K382) and activation of p53, and subsequent p53/p21-mediated senescent “memory.” In contrast, senescent “memory” was abrogated by overexpression of SIRT1 or knockdown of p300. Interestingly, we found that SIRT1 and p300 could regulate each other in response to HN stimulation, suggesting that a delicate balance between acetyltransferases and deacetylases may be particularly important for sustained acetylation and activation of non-histone proteins (such as p53), and eventually the occurrence of “metabolic memory.” Furthermore, we found that RSV or MET treatment prevented senescent “memory” by modulating SIRT1/p300/p53/p21 pathway. Notably, early and continuous treatment of MET, but not RSV, was particularly important for preventing senescent “memory.” In conclusion, short-term high glucose stimulation could induce sustained endothelial senescence via SIRT1/p300/p53/p21 pathway. RVS or MET treatment could enhance SIRT1-mediated signaling and thus protect against senescent “memory” independent of their glucose lowering mechanisms. Therefore, they may serve as promising therapeutic drugs against the development of “metabolic memory.”

Neuroprotection of Neuro2a cells and the cytokine suppressive and anti-inflammatory mode of action of resveratrol in activated RAW264.7 macrophages and C8–B4 microglia

Chronic inflammation is a hallmark of neurodegenerative disease and cytotoxic levels of nitric oxide (NO) and pro-inflammatory cytokines can initiate neuronal death pathways. A range of cellular assays were used to assess the anti-inflammatory and neuroprotective action of resveratrol using murine microglial (C8–B4), macrophage (RAW264.7) and neuronal-like (Neuro2a) cell lines. We examined the release of NO by Griess assay and used a Bioplex array to measure a panel of pro- and anti-inflammatory cytokines and chemokines, in response to the inflammatory stimuli lipopolysaccharide (LPS) and interferon-γ (IFN-γ).Resveratrol was a potent inhibitor of NO and cytokine release in activated macrophages and microglia. The activity of resveratrol increased marginally in potency with longer pre-incubation times in cell culture that was not due to cytotoxicity. Using an NO donor we show that resveratrol can protect Neuro2a cells from cytotoxic concentrations of NO. The protective effect of resveratrol from pro-inflammatory signalling in RAW264.7 cells was confirmed in co-culture experiments leading to increased survival of Neuro2a cells. Together our data are indicative of the potential neuroprotective effect of resveratrol during nitrosative stress and neuroinflammation.

Protection of Lotus Seedpod Proanthocyanidins on Organs and Tissues under High-intensity Excercise.

Lotus seedpod proanthocyanidins (LSPC) as a kind of polyphenols is widely used in medicines, cosmetics, health products. High-intensity exercise can cause damage to the body's organs and tissues. Different doses of LSPC is given to mice to check the function of protect effect to the body's organs and tissues under high-intensity exercise. The hemoglobin (HB) content, red blood cell (RBC) number and white blood cell (WBC) number were tested for mice after exercise. The activity of superoxide dismutase (SOD) and the contents of glutathione (GSH) and malondialdehyde (MDA) in muscle and viscera were evaluated. The result showed that LSPC can effectively reduce inflammation reaction in the body of mice with high intensity exercise, alleviate oxidative stress-induced injury of tissues and organs, and execute protective function on skeletal muscle and cardiac muscle. And the LSPC could enhance myocardial anti-oxygen and enzymatic activity which suggests the protective effects of resveratrol against exercise-induced myocardial damage in mice.

Protective effects of resveratrol in ochratoxin A and citrinin-induced oxidative stress

Protective effects of resveratrol in ochratoxin A and citrinin-induced oxidative stress