Doses Of Resveratrol Research Articles

Effects of resveratrol on macrophages after phagocytosis of Candida glabrata

Candida glabrata is believed to be the underlying cause of many human ailments, including oral, gastrointestinal, and vaginal disorders. C. glabrata-caused deep-seated infections, coupled with its resistance to antifungal drugs, may contribute to a high mortality rate. Resveratrol is a polyphenol and can achieve better therapeutic effects when administered in combination with micafungin, but the underlying molecular mechanisms remain unknown. Here, we investigate the effects of varying doses of resveratrol on the proliferation, apoptosis, and activity of macrophages, which were co-cultured with micafungin-pretreated C. glabrata. Resveratrol can restore the decreased proliferative activity of macrophages caused by the phagocytosis of C. glabrata. Further investigations demonstrated that this restoration ability exhibited a dose-dependent manner, reaching the highest level at 200 µM of resveratrol. Resveratrol tended to be more effective in inhibiting macrophage apoptosis and reducing reactive oxygen species (ROS) levels with concentration increases. In addition, at medium concentrations, resveratrol may down-regulate the expression of most inflammatory cytokines, whereas at high concentrations, it started to exert pro-inflammatory functions by up-regulating their expressions. Macrophages may shift from an anti-inflammatory (M2) phenotype to an inflammatory (M1) phenotype by resveratrol at 200 µM, and from M1 to M2 at 400 µM. Our research shows that resveratrol with micafungin are effective in treating C. glabrata infections. The resveratrol-micafungin combination can reduce the production of ROS, and promote the proliferation, inhibit the apoptosis, and activate the polarization of macrophages in a dose-dependent manner. This study offers insights into how this combination works and may provide possible direction for further clinical application of the combination.

Toluenin Nitrik Oksit Üretimine Etkisinin ve Resveratrolün Koruyucu Özelliklerinin Araştırılması

Amaç: Organik çözücü olarak en çok tercih edilen Toluendir. Toluene uzun süre maruz kalmak ciddi sağlık sorunlarına neden olur. Uluslararası Kanser Araştırmaları Birliği (IACR), tolüeni "insanlar için muhtemelen kanserojen" (Grup 2B) olarak sınıflandırmıştır. Bu sınıflandırma, toluenin potansiyel kanserojen etkilere sahip olabileceğini belirtir. Toluene maruz kalma, reaktif nitrojen türlerinin ve reaktif oksijen türlerinin oluşumuyla bağlantılı olup, doğrudan doku hasarına ve çeşitli antioksidan sistemlerin değişmesine neden olur. Polifenol yapısında olan resveratrol, bitkilerde önemli etkilere sahip bir moleküldür. İnsanlarda da olumlu etkilere sahip olduğu bilinmektedir. Bu çalışmada, kardiyovasküler, nörolojik, immünolojik ve diğer birçok sistemde biyolojik düzenleyici olarak önemli bir role sahip olan nitrik oksit üretimine toluene maruz kalmanın etkisi ve resveratrolün koruyucu özellikleri araştırılmıştır.
 
 Yöntem: Tolüenin 900mg/kg dozu erkek sıçanlara (250-350gr Wistar-Albino) intraperitoneal yolla uygulanırken resveratrol 5, 10 ve 20mg/kg dozları aynı yolla altı gün boyunca uygulanmıştır. Karaciğer dokusunda ve serumda nitrik oksit seviyeleri ve nitrik oksit sentaz aktiviteleri araştırılmıştır.
 
 Bulgular: Veriler, karaciğer dokusunda ve serumda nitrik oksit seviyesinin arttığını ve toluen uygulamasını takiben yüksek nitrik oksit sentaz aktivitesini gösterdi. Resveratrolün çeşitli dozlarının uygulanmasından sonra karaciğerde nitrik oksit seviyelerinde ve nitrik oksit sentaz aktivitesinde önemli azalmalar gözlendi.
 
 Sonuçlar: Sonuçlarımız yüksek dozda toluenin nitrik oksit üretimini tetiklediğini, resveratrolün ise koruyucu özelliklere sahip olduğunu gösterdi.

Effect of resveratrol and curcumin and the potential synergism on hypertension: A mini-review of human and animal model studies.

Resveratrol (RES) and curcumin (CUR) are two of the most extensively studied bioactive compounds in cardiovascular research from the past until today. These compounds have effectively lowered blood pressure by downregulating the renin-angiotensin system, exerting antioxidant effects, and exhibiting antiproliferative activities on blood vessels. This study aims to summarize the results of human and animal studies investigating the effects of CUR, RES, and their combination on hypertension and the molecular mechanisms involved. The published trials' results are controversial regarding blood pressure reduction with different doses of RES and CUR, highlighting the need to address this issue.

Comprehensive review of resveratrol as a feed additive in dairy cows: exploring its potential diverse effects and implications.

Heat stress and growing demand for dairy products in tropical regions exert metabolic pressure on dairy cows, leading to metabolic diseases and economic losses. Resveratrol (RSV) is known for its numerous beneficial health effects and can be used as a barrier against metabolic abnormalities and prevent economic losses. Several studies have investigated the effects of RSV in humans and various animal species. In this review, we attempted to investigate the effects of RSV from different aspects so that we could have a practical proposal for its utilization in dairy cows. RSV was found to have potential antioxidant, anti-inflammatory, anti-obesity, and antimicrobial effects, leading to improved reproductive performance. It is interesting that the effect of RSV on the microbial population leads to a significant decrease in methane emissions. However, high doses of RSV have been associated with possible adverse effects, underscoring the dose dependence of its efficacy. In conclusion, RSV polyphenol at optimal doses is a promising agent for the prevention and treatment of metabolic abnormalities in dairy cows, based on our literature review and study results.

Comparison of Effects of Different Doses of Resveratrol on Methotrexate Induced Toxic Effect on Jejunum in Adult Albino Rats

Comparison of Effects of Different Doses of Resveratrol on Methotrexate Induced Toxic Effect on Jejunum in Adult Albino Rats

The anti-obesity effects of resveratrol on the 3T3-L1 adipocytes.

Obesity is a severe health problem worldwide due to its association with various adverse health consequences. The present study aims to evaluate the anti-obesity effects of resveratrol, as a natural polyphenol, on the 3T3-L1 adipocytes. PubMed, Scopus, ScienceDirect, Web of Sciences, and Google Scholar databases were searched up to March 2022 using relevant keywords. All original articles, written in English, evaluating the anti-obesity effects of resveratrol on the 3T3-L1 adipocytes were eligible for this review. Initially, 4361 records were found in the electronic search databases. After removing duplicates and irrelevant studies according to the title and abstract, the full text of the 51 articles was critically screened and 38 in vitro studies were included in this review. Except for one case, all of these studies reported that different doses (ranged 1-200 μM) of resveratrol treatment have anti-obesity effects on 3T3L1 adipocytes through various mechanisms such as induction of apoptosis, a decrease of fat accumulation and adipogenesis, promotion of white adipocytes browning, inhibition of preadipocyte proliferation and consequent differentiation, and up-regulation of miRNA that involved in the antiadipogenic and triacylglycerol metabolism in white adipose tissue. The findings indicate that resveratrol has anti-obesity effects. Therefore, resveratrol treatment could be used to prevent and treat obesity and its related disorders. Well-designed randomized clinical trials with different doses of resveratrol are recommended to be performed on obese subjects.

Resveratrol Preconditioning Mitigates Ischemia-Induced Septal Cholinergic Cell Loss and Memory Impairments.

Cholinergic cells originating from the nuclei of the basal forebrain (BF) are critical for supporting various memory processes, yet BF cholinergic cell viability has not been explored in the context of focal cerebral ischemia. In the present study, we examined cell survival within several BF nuclei in rodents following transient middle cerebral artery occlusion. We tested the hypothesis that a previously established neuroprotective therapy-resveratrol preconditioning-would rescue BF cell loss, deficits in cholinergic-related memory performance, and hippocampal synaptic dysfunction after focal cerebral ischemia. Adult (2-3-month old) male Sprague-Dawley rats or wild-type C57Bl/6J mice were injected intraperitoneally with a single dose of resveratrol or vehicle and subjected to transient middle cerebral artery occlusion using the intraluminal suture method 2 days later. Histopathological, behavioral, and electrophysiological outcomes were measured 1-week post-reperfusion. Animals with reduction in cerebral blood flow <30% of baseline were excluded. Cholinergic cell loss was observed in the medial septal nucleus and diagonal band of Broca following transient middle cerebral artery occlusion. This effect was prevented by resveratrol preconditioning, which also ameliorated transient middle cerebral artery occlusion-induced deficits in cognitive performance and hippocampal long-term potentiation. We demonstrate for the first time that focal cerebral ischemia induces cholinergic cell death within memory-relevant nuclei of the BF. The preservation of cholinergic cell viability may provide a mechanism by which resveratrol preconditioning improves memory performance and preserves functionality of memory-processing brain structures after focal cerebral ischemia.

Resveratrol; a Double-Edged Sword Antioxidant Agent for Preserving Platelet Cell Functions During Storage; Molecular Insights.

In the current study we have aimed to find the effects of Resveratrol treatment on platelet concentrates (PCs) at the dose dependent manner. We have also attempted to find the molecular mechanism of the effects. The PCs, have received from Iranian blood transfusion organization (IBTO). Totally 10 PCs were studied. The PCs divided into 4 groups including untreated (control) and treated by different dose of Resveratrol; 10, 30 and 50 µM. Platelet aggregation and total reactive oxygen species (ROS) levels were evaluated at day 3 of PCs storage. In silico analysis was carried out to find out the potential involved mechanisms. The aggregation against collagen has fallen dramatically in all studied groups but at the same time, aggregation was significantly higher in the control versus treated groups (p<0.05). The inhibitory effect was dose dependent. The aggregation against Ristocetin did not significantly affect by Resveratrol treatment. The mean of total ROS significantly increased in all studied groups except those PCs treated with 10 µM of Resveratrol (P=0.9). The ROS level significantly increased with increasing Resveratrol concentration even more than control group (slope=11.6, P=0.0034). Resveratrol could potently interact with more than 15 different genes which, 10 of them enrolled in cellular regulation of the oxidative stress. Our findings indicated that the Resveratrol affect the platelet aggregation at the dose dependent manner. Moreover, we have also found that the Resveratrol play as double-edged sword in the controlling oxidative state of the cells. Therefore, Using the optimal dose of Resveratrol is the great of importance.

Autophagic-Related Anticancer Effect of Grapes Extract and Tomatoes Extract: Ex-Vivo Study

Cells undergo autophagy to save themselves from injury, but progressive autophagy can cause cell death. This study characterized and compared the effect of grape (resveratrol) and tomato (lycopene) extracts and their combination on modulating autophagy-related miRNA and its target gene in squamous cell carcinoma cell line. Docking analysis for extracts and selected genes was performed. Methyl Thiazol Tetrazolium assays were used to assess the cytotoxicity of extracts and their combination toward HEp-2 cells. qRT-PCR was used to quantify changes in gene expression. Data were statistically analyzed. miRNA-20a was identified as a potential effector in laryngeal cancer, and sequestosome-1 (SQSTM1) was its target gene. Docking analysis showed that resveratrol interacted with miRNA-20a and showed less affinity toward SQSTM1. Hydrogen bonds and hydrophobic interactions were predicted. In contrast, lycopene showed less affinity toward miRNA-20a than resveratrol. Increasing doses of resveratrol, lycopene, and their combination induced a statistically significant reduction in mean percent viability and mean fold changes of miRNA-20a and SQSTM1 expression in treated HEp-2 cells. Pearson’s correlation showed a statistically significant positive correlation between miRNA-20a and SQSTM1 (R=0.812, p≤0.001). Grape and tomato extracts and their combination display promising cytotoxicity against HEp-2 cells in a dose- and time-dependent fashion. Both extracts reduce the expression of miRNA-20a and SQSTM1 with subsequent inhibition autophagy and promotion of apoptosis in HEp-2 cells.&#x0D;

Integrated analysis of lncRNA and mRNA for the apoptosis of porcine ovarian granulosa cells after polyphenol resveratrol treatment.

Resveratrol (RES) is a non-flavonoid polyphenol compound that can be involved in follicular development and ovulation. However, the mechanism by which resveratrol regulates the apoptosis of porcine ovarian granulosa cells (POGCs) through long non-coding RNA (lncRNA) is poorly understood. We generated POGCs models of different doses of RES (0, 25, 50, 75, and 100 μM). It was observed that the cell viability was the highest in the 50 μM group, and the highest apoptosis rates were recorded in the 100 μM group. Therefore, a control group (n = 3, 0 μM RES group), a low RES group (n = 3, 50 μM RES group), and a high RES group (n = 3, 100 μM RES group) of POGCs were created for next RNA sequencing. Gene Ontology (GO) indicated that differentially expressed lncRNAs associated with apoptotic process were highly enriched. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of lncRNA target genes found that the Wnt signaling pathway and PI3K-Akt signaling pathway were both enriched. Furthermore, we constructed lncRNA-mRNA networks related to Metabolic and Cell Apoptosis, respectively. In the networks, five key-lncRNAs were screened, which may play a significant role in the process of POGCs metabolism and apoptosis. Furthermore, we focused on the function of a lnc-GAM (lncRNA associated with Granulosa cells Apoptosis and Metabolism) and verified that lnc-GAM could influence cell apoptosis in POGCs development by affecting the mRNA expression of apoptosis-related markers, and also affects the secretion of steroid hormones and related genes expression in POGCs cultured in vitro. Our study provides seminal data and important new insights into the regulation of reproductive mechanisms in porcine and other female mammals.

Resveratrol Improves the Progression of Osteoarthritis by Regulating the SIRT1-FoxO1 Pathway-Mediated Cholesterol Metabolism.

Osteoarthritis (OA) is considered a metabolic disorder. This study investigated the effect of resveratrol (RES) on cholesterol accumulation in osteoarthritic articular cartilage via the silent information regulator 1 (SIRT1)/forkhead transcription factor (FoxO1) pathway. Interleukin (IL)-1β-treated chondrocytes that mimic OA chondrocytes were used in in vitro experiments. The optimal RES concentration was selected based on the results of chondrocyte proliferation in the Cell Counting Kit-8 assay. Western blotting, immunofluorescence, and reverse transcription-quantitative polymerase chain reaction were performed. For the animal experiments, mice were randomly divided into the RES group (n = 15), medial meniscus destabilization group (n = 15), and sham group (n = 15), and each group received the same dose of RES or saline. Articular cartilage tissue was obtained eight weeks after surgery for relevant histological analysis. Clinical tissue test results suggest that downregulation of the SIRT1/FoxO1 pathway is associated with cholesterol buildup in OA chondrocytes. For the in vitro studies, RES increased the expression of SIRT1 and phosphorylation of FoxO1 in IL-1β-treated chondrocytes, promoted the expression of cholesterol efflux factor liver X receptor alpha (LXRα), and inhibited the expression of cholesterol synthesis-associated factor sterol-regulatory element binding proteins 2 (SREBP2). This reduced IL-1β-induced chondrocytes cholesterol accumulation. SIRT1 inhibition prevented the RES-mediated reduction in cholesterol buildup. Inhibiting FoxO1 but not SIRT1 reduced FoxO1 phosphorylation and increased cholesterol buildup in cultured chondrocytes. Additionally, in vivo experiments have shown that RES can alleviate cholesterol buildup and pathological changes in OA cartilage. Our findings suggest that RES regulates cholesterol buildup in osteoarthritic articular cartilage via the SIRT1/FoxO1 pathway, thereby improving the progression of OA.

Hsp27, Hsp60, Hsp70, or Hsp90 depletion enhances the antitumor effects of resveratrol via oxidative and ER stress response in human glioblastoma cells

Therapeutic resistance of gliomas is still a crucial issue and closely related to induced heat shock response (HSR). Resveratrol (RSV) is a promising experimental agent for glioblastoma (GB) therapy. However, the role of heat shock protein (Hsp)27, Hsp60, Hsp70, and Hsp90 on the therapeutic efficacy of RSV remains unclear in gliomas. Herein, small interfering (si)RNA transfection was performed to block Hsp expressions. RSV treatments reduced glioma cells' viability dose- and time-dependent while keeping HEK-293 normal cells alive. Furthermore, a low dose of RSV (15 µM/48 h) offered protection against oxidative stress and apoptosis due to Hsp depletion in healthy cells. On the contrary, in glioma cells, RSV (15 µM/48 h) increased ROS (reactive oxygen species) production, led to autophagy and induced endoplasmic reticulum (ER) stress and apoptosis, and reduced 2D- and 3D-clonogenic survival. Hsp27, Hsp60, Hsp70, or Hsp90 depletion also resulted in cell death through ER stress response and ROS burst. Remarkably, the heat shock response (increased HSF1 levels) due to Hsp depletion was attenuated by RSV in glioma cells. Collectively, our data show that these Hsp silencings make glioma cells more sensitive to RSV treatment, indicating that these Hsps are potential therapeutic targets for GB treatment.

Abstract A020: Exploring the effects of resveratrol on the gut microbiome in high fat diet-fed BRAFV600E mutant mice

Abstract The polyphenol resveratrol, widely known for its cancer protective activities has been shown to protect against the pro-tumorigenic effects induced by high-fat diets (HFD) in mouse models of colorectal cancer (CRC). Although, the mechanisms of actions of this compound in humans still remain elusive, recent studies suggest its effects may be mediated partly through its interaction with the gut microbiota. Here we sought to determine the changes induced by HFD on the intestinal microbiome and the impact of resveratrol supplementation on these alterations in a mouse model of BRAFV600E mutant CRC. BRAFV600E; BRAFWT (wild-type) mice were randomised into 8 groups and fed either a standard diet or HFD supplemented with low or high-dose of resveratrol (0.7mg/kg/day and 14mg/kg/day, respectively) for 6-weeks. The mouse faecal microbial profile was then assessed by targeting the V3-V4 area of the bacterial 16S rRNA gene. Consumption of HFD was associated with significant alternations in the gut microbiome composition in both BRAFV600E and BRAFWT based on beta-diversity analysis (PADONIS&amp;lt;0.05). HFD increased the Firmicutes and Clostridia abundance in BRAFWT compared to animals on a standard diet (P&amp;lt;0.01, P&amp;lt;0.008 respectively), while in BRAFV600E mice, alterations were observed in lower taxonomic levels including the enrichment of Faecalibaculum (P&amp;lt;0.02) and growth inhibition of Lactobacillus johnsonhii (P&amp;lt;0.05). High-dose resveratrol resulted in significant differences in the microbial composition compared to HFD-treated group in the BRAFV600E mice (PADONIS&amp;lt;0.05) but not in BRAFWT . Resveratrol administration did not counteract the HF-induced taxonomic changes but high-dose resveratrol changed Muribaculum, and UBA181 genera abundances in BRAFV600E mice (P&amp;lt;0.001 and P&amp;lt;0.05 respectively) compared to HF-treated mice. Low dose resveratrol had no significant effects on bacterial abundance in both BRAFV600E and BRAFWT mice. It was also observed that BRAFV600E mutation influenced the gut microbiome independently of diet based on beta and alpha-diversity (PADONIS&amp;lt;0.05, PChao1&amp;lt;0.05 respectively). Resveratrol administration modified the gut microbiota composition of BRAFV600E mice but did not completely reverse the HFD-induced changes indicating that alternative mechanisms may contribute to the protective effects of resveratrol in this mouse model. Citation Format: Despoina Theofanous, Hong Cai, Karen Brown. Exploring the effects of resveratrol on the gut microbiome in high fat diet-fed BRAFV600E mutant mice [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A020.

Resveratrol exerts anxiolytic-like effects through anti-inflammatory and antioxidant activities in rats exposed to chronic social isolation

Emerging evidence has confirmed resveratrol's (RES) antioxidant, anti-inflammatory, and antidepressant effects. The beneficial effects of RES were confirmed for several emotional and cognitive deficits. This research aimed to assess the impacts of RES on behavior and hippocampal levels of anti-inflammatory and pro-inflammatory factors in rats exposed to chronic social isolation (SI) stress, which is known to induce mental disorders such as depressive-like behavior. The animals were treated by RES (20, 40, or 80 mg/kg/intraperitoneally) for 28 days following a 28-day exposure to stress. Behavioral tests, including the forced swim test (FST), open-field test (OFT), tail suspension test (TST), and sucrose preference test (SPT), assessed depressive symptoms. Finally, the animals were sacrificed, and molecular studies (qPCR and ELISA) were performed. Exposure of animals to SI dramatically increased the immobility of animals in TST and FST, enhanced the time spent in the open-field peripheral zone of the OFT, and reduced the sucrose preference rate. In addition, SI increased serum levels of corticosterone and hippocampal content of MDA, whereas it reduced hippocampal SOD and CAT activities. Moreover, SI upregulated the expression of IL-10, IL-18, and IL-1β and downregulated the expression of TGF-β in the hippocampus. RES treatment (40 & 80 mg/kg) significantly improved the behavioral alterations through the modulation of neuroinflammation and oxidative stress. The 20 mg/kg RES dose was inefficient for treating SI-induced depressive-like behavior. These results indicated that RES attenuated depressive-like behavior in prolonged stressed animals. These properties might be associated with RES-mediated improvements in serum corticosterone and hippocampal inflammatory and oxidative stress biomarkers.

Resveratrol promotes liver cell survival in mice liver-induced ischemia-reperfusion through unfolded protein response: a possible approach in liver transplantation

BackgroundIschemia-reperfusion (I/R) of the liver is a multifactorial condition that happens during transplantation and surgery. The deleterious effects of I/R result from the acute production of reactive oxygen species (ROS), which can trigger immediate tissue damage and induce a series of destructive cellular responses, including apoptosis organ failure and inflammation. The production of ROS in the I/R process can damage the antioxidant system and cause liver damage. Resveratrol has been shown to have antioxidant properties in several investigations. Here, we address the therapeutic effect of resveratrol on I/R-induced liver injury by focusing on unfolded protein response (UPR) signaling pathway.MethodsFive minutes before reperfusion, resveratrol was injected into the tail vein of mice. They were ischemic for 1 h and then re-perfused for 3 h before being slaughtered (I/R). The activity of liver enzymes and the expression levels of genes involved in the unfolded protein response pathway were used to measure the hepatic damage.ResultsOur results revealed that the low dose of resveratrol (0.02 and 0.2 mg/kg) post-ischemic treatment significantly reduced the ALT and AST levels. In addition, compared with the control group, the expression of UPR pathway genes GRP78, PERK, IRE1α, CHOP, and XBP1 was significantly reduced in the resveratrol group. In the mice that received lower doses of resveratrol (0.02 and 0.2 mg/kg), the histopathological changes induced by I/R were significantly improved; however, the highest dose (2 mg/kg) of resveratrol could not significantly protect and solve the I/R damage.ConclusionThe findings of this study suggest that hepatic ischemia occurs after liver transplantation and that receiving low-dose resveratrol treatment before reperfusion may promote graft survival through inhibition of UPR arms, especially PERK and IRE1α.

Histopathological, physiological and biochemical assessment of resveratrol nanocapsules efficacy in bleomycin-induced acute and chronic lung injury in rats

Acute lung injury (ALI) is a life-threatening illness which may progress to chronic pulmonary fibrosis (CPF). Resveratrol (RSV), a natural polyphenol, is known to exert several pharmacological effects on lung injury. However, its physicochemical properties and pharmacokinetic profile limit its clinical applications. In this study, RSV was loaded into lipid nanocapsules (LNCs) aiming to overcome these limitations. RSV-LNCs were prepared by phase inversion method and showed small uniform particle size (∼55 nm, PdI 0.04) with high entrapment efficiency >99%. The efficacy of RSV-LNCs in the prophylaxis against ALI and treatment of CPF was investigated in bleomycin-induced lung injury. For assessment of ALI, rats were administered a single oral dose of RSV (10 mg/kg) either free or as RSV-LNCs 4 h before bleomycin and euthanized 3 days later. For CPF, treatments in the same dose were given daily from days 10–20 after bleomycin and rats were euthanized on day-21. Results showed enhanced beneficial role for RSV-LNCs, compared to RSV, in the prevention of ALI as demonstrated by preservation of pulmonary microscopic and ultrastructural architecture and improvement of pulmonary functions. Analysis of BALF revealed reduction in oxidative stress markers, IL-6 level, leukocytosis and neutrophilia. iNOS and c-caspase 3 immunohistochemical expression and CD68+ cells immunofluorescence were inhibited. However, RSV-LNCs failed to show any improvement in oxidative stress, chronic inflammation, apoptosis and collagen deposition in CPF. In conclusion, RSV-LNCs are promising nanoplatforms for mitigating ALI detrimental effects. Future research investigating higher doses and longer durations of treatment is recommended to evaluate RSV-LNCs anti-fibrotic potential in CPF.

Resveratrol Glycosides Impede Microglial Apoptosis and Oxidative Stress in Rats for Spinal Cord Injury

Spinal cord injury (SCI) usually occurs after severe trauma, which can lead to detrimental and unpredictable secondary diseases, including dyskinesia, paraplegia and even quadriplegia, resulting in seriously reduced quality of life among these patients. Oxidative damage is one of the major pathogenic factors of SCI. Resveratrol biologically exerts a significant antioxidant activity by increasing the levels of antioxidants and sequentially scavenging free radicals, so as to protect multiple organs from damage. This study investigates whether resveratrol can function as a protective mediator in SCI and the underlying mechanisms, aiming to provide a theoretical hint for the treatment of SCI. After establishment of SCI model in rats, serial doses of resveratrol were administrated. Afterwards, the therapeutic effects of resveratrol glycosides were evaluated by analyzing the motor function, spinal cord edema, cellular apoptosis and oxidative reaction in rats. Eventually, the potential mechanisms of resveratrol glycosides were studied via Western blotting. Our results showed that the pro-apoptosis proteins were highly expressed in the spinal cord tissue of rats after SCI. In comparison with healthy rats, those with SCI exhibited significant widespread dead neurons, glial cell apoptosis, oxidative stress and more serious functional defects. Nevertheless, resveratrol glycosides can ameliorate oxidative stress, inhibit the apoptosis of glial cells and neuronal death after SCI. Importantly, it can induce the activation of the Nrf2/HO-1 signal transduction pathway that mediated the alleviation of SCI in rats. Resveratrol can improve motor dysfunction after SCI, which may be a result of its anti-oxidation and anti-apoptotic effects via modulating the Nrf2 signal transduction pathway of microglia, which provides a new idea for the treatment of SCI.

Resveratrol decreases local inflammatory markers and systemic endotoxin in patients with aggressive periodontitis.

Background:Inflammation is hypothesized to contribute to the pathogenesis of periodontitis. Resveratrol (RV) is known for its anti-inflammatory properties. The purpose of this study was to investigate the inhibitory effect of RV on local inflammatory markers and systemic endotoxin in patients with periodontitis.Methods:A total of 160 patients with periodontitis were enrolled in this study. The selected patients were randomly divided into four groups and received placebo, high-dose (500 mg/d) of RV (HRV, n = 40), middle-dose (250 mg/d) of RV (middle dose RV (MRV), n = 40) and low-dose (125 mg/d) of RV (low dose RV (LRV), n = 40) with orally administration. All patients received an 8-week treatment. The periodontal status of patients with periodontitis was recorded by using clinical attachment level (CAL), bleeding index (BI), oral hygiene index-simplified (OHI-S), and probing pocket depth (PPD). The levels of inflammatory markers in serum and gingival crevicular fluid (GCF), and systemic levels of endotoxin were evaluated using high sensitivity enzyme-linked immuno sorbent assay.Results:Outcomes showed that symptoms of periodontitis determined by CAL, BI OHI-S and PPD were improved by RV compared to placebo. RV treatment decreased inflammatory markers in serum and GCF compared to placebo in patient with periodontitis. Systemic endotoxin declined more in the RV group than the placebo-treated group.Conclusion:In conclusion, data in the current study indicate that RV is an efficient drug for the treatment of patients with periodontitis. The findings of the present study find that RV inhibits systemic local inflammatory markers and systemic endotoxin and suggest that 500 mg/d RV is the ideal dose for patients with periodontitis.

Estimation the Safety of Parenteral Resveratrol in Mice

Resveratrol is polyphenolic compound has many biochemical and biological effects on several organs. Therefore, resveratrol can be used to treat many diseases. The aim was to evaluate resveratrol safety when used in a parenteral single bolus dose. This study was conducted on 60 mice (30 males and 30 females). Each male and female mice divided into 6 groups (five mice per group). All mice groups given 1% DMSO and five different doses of resveratrol (5, 2.5, 1.25, 0.625, 0.312) gm/kg intraperitonially given to five groups respectively. The mice were continuously monitored during 14 days. The number of deaths, changes in general behavior, changes in physiological activity, and signs of toxicity were reported. On day 15 blood was collected using a jugular vein puncture to obtain blood samples for hematological and biochemical analysis. All mice were euthanized under anesthesia. The heart, lung, liver, kidney, and gonads were dissected and sent for histopathological study. The result showed that at dose 0.312gm/kg neither signs of toxicity nor death were detected. The LD50 dose was 1.18 g/kg for female and 1.07 g/kg for male mice. The body weight change, biochemical and hematological assay, revealed that at doses 1.25 g/kg,0.625,0.312 g/kg for both sexes no significant changes had reported in comparison with a control group (p?0.05). Histopathological examination revealed that at doses 1.25 g/kg for both sexes no significant tissue changes had reported in comparison with a control group (p?0.05). In conclusion resveratrol has dose-dependent toxicity when used intraperitoneally in Swiss Albino mice and the non-observed adverse effect level at dose 0.312 g/kg.

Resveratrol promotes bone mass in ovariectomized rats and the SIRT1 rs7896005 SNP is associated with bone mass in women during perimenopause and early postmenopause

Objective This study aimed to examine the effects of SIRT1 agonist resveratrol on bone mass in ovariectomized (OVX) rats and the SIRT1 single-nucleotide polymorphism (SNP) rs7896005 on bone mass in women during menopause and early postmenopause. Methods An animal experiment was conducted on rats that were sham-operated (SHAM), OVX or OVX and different administered doses of resveratrol. Serum markers and femur microstructure and staining were assessed. A cross-sectional study was conducted in women undergoing menopause. SIRT1 protein and SIRT1 SNP rs7896005 were evaluated. Results OVX rats administered resveratrol, especially high doses, showed lower bone loss than OVX rats. Serum osteoprotegerin (OPG) and femur SIRT1, β-catenin and bone mineral density (BMD) were significantly increased, whereas receptor activator of NF-κB ligand (RANKL) was significantly decreased. Serum SIRT1 levels were significantly lower in women with low bone mass (p < 0.01). Women with the CA genotype of rs7896005 had lower bone mass than those with the CC genotype. The A allele showed a significant negative effect on bone loss risk (odds ratio = 3.48; p = 0.025). Conclusions Resveratrol stimulated SIRT1 expression and Wnt/β-catenin signaling to promote bone mass in rat femurs. Among women in perimenopause and early postmenopause, SIRT1 protected bone mass, and the A allele of SIRT1 rs7896005 was a risk factor for reduced bone mass.