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5 Amazing Facts About Resveratrol That You Need to KnowResveratrol and immune system -
One explanation may be that resveratrol is not the only compound with health benefits in wine. Additionally, polyphenols are also found in grape skin and may play a protective role in heart disease.
Is drinking red wine in moderation the answer to good health? In a recent study, the effects of resveratrol on the immune response were examined. It was found that resveratrol activated Sirt1, which may increase antioxidant and anti-inflammatory properties.
Low doses of resveratrol were shown to rapidly stimulate T cells that could lead to the DNA damage response pathway.
Activation of p53 can lead to expression of gene products that regulate cell metabolism and oxidative phosphorylation. This data highlighted the role that stress plays in T cell and metabolic changes that can occur. Resveratrol can stimulate the metabolic reprogramming of T cells to enhance the immune response.
The use of resveratrol in treatments for various illnesses including diabetes, cancer, and mental health needs to be further studied. We offer a comprehensive toolset from isolation, modification, and detection.
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Antibody Search Tool. Apoptosis Detection Guide. RSV targets several inflammatory components and exerts immune-regulatory effects on immune cells Multhoff and Radons, ; Malaguarnera, Numerous important mediators in the cell are targets of RSV such as sirtuins, adenosine monophosphate kinase AMP , NF- κ B, inflammatory cytokines, and cellular processes such as gluconeogenesis, lipid metabolism, mitochondrial biogenesis, angiogenesis, and apoptosis Malaguarnera, Despite the numerous studies demonstrating the possible role of RSV as a radio-protective compound, little is known about its ability to modify the effect of radiation in normal and cancer cells Dobrzynska, Thus, in the current study, the ability of resveratrol to modulate the effect of radiation in normal tissue post whole body gamma irradiation was thoroughly investigated.
RSV effects on the number of circulating endothelial cells CECs , which is increased during irradiation therapy and considered as a marker of apoptosis, was also investigated in this work.
RSV was administered intraperitonealy I. every 24 h for 30 days prior to irradiation. Irradiation protocol was approved by the Atomic Energy Commission of Syria according to the IAEA regulations and safety measures. The abdomen was opened through a midline incision; then a 25G needle was inserted in the inferior vena cava to collect blood into a citrate containing tube for the immuno-magnetic separation IMS analysis of CECs; then, the animals were sacrificed via cervical dislocation and the liver was dissected, rinsed with PBS.
Hepatocytes and Kupffer cells isolated from each liver sample were rinsed with PBS, then suspended in 1 ml of Tris-Urea-CHAPS lysing buffer 50 mM Tris. Cl, pH 7.
Supernatant was directly used to quantify the cytokines using Rat Th Cytokine panel plex kit, BioLegend ® , Cat. Briefly, 25 µl of the cleared supernatant sample was incubated with beads coated with each anti-cytokine antibodies then washed and incubated with detection antibodies before washing and analyzing.
Standard cytokine panel cocktail was utilized to build the standard curves, which were then used to calculate cytokine concentrations. BD Biosciences FCAP software was deployed to calculate cytokine concentrations.
Three replicates of each liver tissue sample were measured. Hepatocytes and Kupffer cells were isolated from Wistar rat livers according to a modified method previously described by Shulman and Nahmias Frozen liver tissue samples were brought into room temperature and rinsed with PBS, then each liver sample weighing 50 mg was minced in a sterile petri dish containing 5 ml of collagenase dissolved in Krebs Ringer Buffer 0.
Krebs Ringer Buffer recipe: Kupffer cells recovered from the band in the supernatant, and hepatocytes recovered from the pellet.
Cells were then washed with PBS and used in other assays. PCR was performed using 0. Mx3OO5P QPCR system Agilent technologies, Germany was used to quantify the expression of target genes according to the procedure described in previous works Khalil et al.
Primer sequences Eurofins Genomics, Germany for the reference and target genes were:. Total protein was extracted from isolated hepatocytes and Kupffer cells by adding 1 ml of ice-cold nondenaturing lysis buffer to 0.
Cells were suspended in lysis buffer by gentle agitation for seconds with a vortex mixer set at medium speed, then the suspension was kept on ice for 15 to 30 min.
IL levels were measured using Interleukin ELISA kit Sigma Aldrich ® , St. Specimens were cut into 5 µm thick sections by cryostat SLEE MNT Cryostat Medical GmbH, Germany , then stained with hematoxylin Flukachemie Gm bHcH, Switzerland and eosine Qualikems laboratory Reagent, India according to standard histological staining procedures.
Stained liver tissues were imaged using a light microscope BX53, Olympus, Japan connected to a personal computer. Endothelial cells were isolated from the whole blood using Dynal M IgG1 immune magnetic beads Dynal AS, Oslo, Norway.
Beads were then washed three times with PBS—BSA—NaN3 to remove excess of antibodies then resuspended with buffer until use. Separation of beads rosetted with endothelial cells from the blood samples required a minimum of 2 min exposure to the magnet.
Three washes were performed to completely remove non-rosetted cells. Endothelial cells were counted using 0. The quality of images was improved by Deltapix software version 1. All experiments were repeated three times, and data were statistically analyzed using a Mann—Whitney U test and presented as the mean ± SD.
All statistical analyses were performed with GraphPad Prism 7. For endothelial cell quantitation, the results were presented as Mean cell number ± SEM.
In addition, RSV administration increased IL levels significantly by approximately 2. No alterations in IL-4, IL-5, and IL levels were observed after administrating RSV at any used dose Figures 2A, B, E.
However, our results showed that IL-4, IL-5, IL-6, IL, and IL levels were significantly increased in irradiated rats compared to non-irradiated non-resveratrol treated control C group. This increase was ~3-fold Figure 2A , 2.
Figure 2 The cytokine profiles in Wistar rat liver produced by Th2 cells, which include A IL-4, B IL-5, C IL-6, D IL10, and E IL in six rat groups. Whereas IL-9, IL A and F , GM-CSF, and IL significantly increased by about 3.
ILA and GM-CSF which enhance pro-inflammatory cytokine production Brembilla et al. The same result was obtained for IL, which somehow decreased by about 0.
Figure 3 The cytokine profiles in Wistar rat liver produced by Th9,Th17, and Th22 cells which include A IL-9, B ILA, C ILF, D GM-CSF and E IL in six rat groups.
IL is a very important anti-inflammatory cytokine, which maintains normal tissue homeostasis Iyer and Cheng, The results of the current study found that RSV induces the production of IL, the most significant anti-inflammatory cytokine among all measured cytokines.
In order to identify the origin of this important anti-inflammatory cytokine induced by RSV administration, we isolated the hepatocytes and Kupffer cells.
RSV increased IL mRNA expression and IL levels in both hepatocytes and Kupffer cells. This increase is further confirmed by an increase in IL10 protein levels extracted from isolated cells Figure 4B.
The concentrations of IL in KCs and in HCs isolated from livers of irradiated rats pretreated with RSV increased by about 2. Figure 4 Effects of a 2 Gy single dose of whole body irradiation and RSV on IL10 relative mRNA gene expression and protein levels in Hepatocytes A , C and Kuppfer cells B, D of Wistar rats.
A histological study on liver tissues was conducted to evaluate the effects of RSV on the histology of hepatic tissue and on the number of Kupffer cells, which are the most abundant immune cells in the liver.
Figure 5 demonstrates that irradiation increased the number of Kupffer cells Figure 5B in the liver of irradiated rats compared to the non-irradiated control Figure 5A. Pretreatment with resveratrol enhanced the CEC counts in peripheral blood, which implies radioprotective effect.
Radiation exposure has been reported to induce several cytokines and growth factors in vivo and in vitro such as TNF-α, IL-1 β , IFN- γ , GM-CSF, IL-4, IL-5, IL-6, IL, IL, and IL, and TGF- β Zhang et al.
IL-2, TNF-α, and INF- γ are pro-inflammatory cytokines produced by Th1 cells and amplifying the inflammatory response Martin et al.
These cytokines were upregulated by irradiation with 2 Gy dose of gamma radiation, and this result was expected as irradiation leads to upregulation of pro-inflammatory cytokines such as TNF-α, IL-1 β , INF- γ , IL-6 Shan et al.
RSV administration before irradiation resulted in a slight inhibition of TNF-α production Figure 1B. It also reduced the levels of INF- γ significantly compared to irradiated non-resveratrol treated control Figure 1C.
This is consistent with a previous study in which resveratrol could significantly reduce the levels of pro-inflammatory factors: TNF-α, IL-1 β , and IL- 6 and greatly promote the expression level of SIRT1 pathway, which is the main pathway of pro-inflammatory inhibition by RSV Schaue et al.
However, in our experiments, IL-2 generated by Th1 cells and IL-6 produced mainly by Th2 cells were the only pro-inflammatory which was upregulated by RSV in rat liver subjected to irradiation Figures 1A and 2C.
Also, it was demonstrated that mRNA and serum levels of IL-2, IL-6, and IL increased in patients post oral administration of resveratrol Multhoff and Radons, In addition, RSV was found to enhance the expression of IL-1 β and IL-6 in the peripheral blood lymphocytes Wendling et al.
These results are in accordance with our results. In fact, the enhanced production of IL-1 β and IL-6 characterizes a pro-inflammatory status contributing to T helper lymphocyte differentiation and function BaGen et al.
Thus, this increase in IL-6 and IL-2 may be involved in tissue repair and regeneration post-irradiation. Furthermore, the immune cells exposed to RSV in the vascular compartment expressing significant levels of IL-1 β or IL-6 are triggered for the adaptive immune response Malaguarnera, GM-CSF is a pro-inflammatory cytokine that acts at the interface between innate and adaptive immunity Rutz et al.
RSV also ominously reduces the production of this pro-inflammatory cytokine Figure 3D which is in agreement with the results reporting that RSV reduces the expression of GM-CSF in TNF-α activated human umbilical vein endothelial cells Wendling et al.
In fact, the Th17 cells play very important roles in autoimmune diseases, which are key initiators of pro-inflammatory responses through recruiting neutrophils and macrophages to injured tissues and via their production of IL, which in turn plays an important role in host defense against infection of extra cellular pathogens.
Moreover, Th17 cells produce IL, which, similar to IL, is beneficial to the host in many inflammatory disorders Schwager et al. However, depending on the target tissue, IL can be pathogenic due to its inherent pro-inflammatory properties, which are further enhanced when IL is released together with other pro-inflammatory cytokines, in particular IL Astry et al.
In fact, RSV, in our study prevents the link of IL and IL Thus, RSV plays a protective role against the unexpected consequences from IL and IL operating together Figures 2B, E.
RSV exhibits an anti-inflammatory profile in macrophages Walle et al. Our results support this role of RSV in KCs of the liver by producing IL, which has a strong anti-inflammatory role in the immune response. RSV enhances hepatocytes as reported in the current study to produce IL response, but as demonstrated in Figures 2D and 3 , the IL production by HCs is less important versus production of IL by KCs that might be due to the increased number of KCs by RSV effect Figure 5D exhorting KCs to produce more anti-inflammatory response mediated by IL in our study Figures 4A, B.
However, this finding indicates that RSV may promote IL mediated immune resolution as reported previously Chung, ; Bonizzi and Karin, ; Ogawa et al. Actually, this result is of a great importance and leads us to conclude that RSV effects after whole body irradiation are mainly via KCs derived-IL and not via HCs.
Moreover, IL plays a very important role in mediating host anti-inflammatory response. Therefore, identifying the cellular sources of IL in addition to the molecular mechanisms that regulate IL expression is critical to developing therapeutic strategies directed against pathology associated with impaired IL production Iyer and Cheng, In fact, these results give a great essential key role to liver KCs in immune response post whole body irradiation as a cellular and molecular target of future pharmacological molecule such as RSV.
Moreover, RSV enhances the expression of the anti-inflammatory cytokine IL-4 produced by Th2 cells Figure 2A post irradiation. In fact, this effect of RSV to enhance the anti-inflammatory response by IL-4 and IL is in accordance with a similar study in mouse bone marrow mesenchymal stem cells for therapeutic purposes reported by other groups Wang et al.
Regarding IL-5 and IL produced by Th2 cells, our data presented in Figures 2A, B, E demonstrated that these cytokines were not affected by RSV administration; in contrast, RSV triggered an insignificant decrease of these cytokines. Actually, our results agree with previous works on the effect of resveratrol in normal tissues RSV10 and RSV compared to controls C.
In fact, it seems that RSV promotes the production of IL Figure 2D and decreases ILA-mediated induction of IL-6 Hwang et al. In a previous study, our group reported a gradual decline in CEC count post irradiation AL-Massarani and Almohamad, Originally, the results of this study Figure 6 suggest that injection of RSV attenuates radiation-induced CEC apoptosis in rats.
This is consistent with previous studies, which demonstrated theprotective role of RSV against apoptosis induced by radiation Zhang et al.
Thus, RSV exerts a radio-protective effect on endothelial cells. Furthermore, our findings clearly demonstrate that RSV can modulate CEC population, which is considered as a good marker of radiation exposure. RSV was found to partially re-populate these cells.
CEC results support the use of RSV as a radio-protector with the potential for radiotherapy application. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation, to any qualified researcher.
This article does not contain any studies with human participants performed by any of the authors. AK supervised the study, analyzed all results and wrote the manuscript. GA-M designed the study and planned the part related to counting of CECs. MB was the scientific adviser and edited the final manuscript.
AE and AA carried out the flow cytometry measurement and analyzed the related results. All authors contributed to the article and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The authors wish to express their deep appreciation to Prof. Ibrahim Othman, the director general of the Atomic Energy Commission of Syria AECS. Thanks is also extended to the member of the technical staff Ms. Israa Banat for technical assistance. Aggarwal, B. Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies.
Anticancer Res. PubMed Abstract Google Scholar. Another nutraceutical with solid science for immune health is resveratrol. Resveratrol is a type of natural phenol produced by several plants in response to injury or attack by pathogens.
Resveratrol can influence multiple inflammatory and non-inflammatory responses, protecting organs and tissues, thanks to its interaction with immune cells and its activity on SIRT1.
More specifically, resveratrol can increase certain circulating immune cells known as gamma delta T cells. These are a subset of T cells that are especially vital to initial inflammatory and immune responses. The results were that resveratrol was safe and well tolerated and was associated with significant increases in the numbers of circulating gamma delta T cells functioning as a first line of defense and a bridge between innate and adaptive responses and regulatory T cells.
In another week study9, subjects were given resveratrol mg orally once daily with a dose escalation by mg increments every 13 weeks, ending with mg twice daily , or placebo. The results were that, compared to the placebo-treated group, resveratrol markedly increased important immune cells including macrophage-derived chemokine, and interleukin IL Resveratrol is a phenol antioxidant which is well known for its role in activating the e SIRT 1 gene.
In turn, this plays a role in immune health, influencing multiple inflammatory and non-inflammatory responses. Resveratrol has specifically been shown to increase levels of important immune cells including gamma delta T cells, macrophage-derived chemokine MDC , and interleukin IL These benefits can be achieved by supplementing with 1, mg daily of resveratrol.
Cision PR Newswire. Mar 03,
Journal Resveratrol and immune system Neuroinflammation volume 14Article number: shstem Cite this article. Metrics Resverstrol. Natural body cleanse utilized multiplex Xmap Natural body cleanse to measure markers of sysstem disease and metalloproteinases MMPs in parallel in CSF imumne plasma samples. Compared to the placebo-treated group, at 52 weeks, resveratrol markedly reduced CSF MMP9 and increased macrophage-derived chemokine MDCinterleukin IL -4, and fibroblast growth factor FGF Compared to baseline, resveratrol increased plasma MMP10 and decreased ILP40, IL12P70, and RANTES. In this subset analysis, resveratrol treatment attenuated declines in mini-mental status examination MMSE scores, change in ADL ADCS-ADL scores, and CSF Aβ42 levels during the week trial, but did not alter tau levels.
Resveratrol and immune system -
In several experimental autoimmune studies, resveratrol has upregulated the binding of Sirt1. Resveratrol also modulates the profile of macrophages in our immune system.
Macrophages come from blood monocytes and contribute to both innate and adaptive immunity by directly destroying microbial invaders as well as priming the adaptive system to begin attacking the same invader.
Depending on which type of macrophages are stimulated, inflammation may be turned up or down. This balance is greatly influenced by cell receptors call Toll Like Receptors TLR. Resveratrol appears to downregulated a specific TLR called TLR4 which influences macrophage activation patterns.
Multiple other macrophage-influencing mechanisms go beyond the scope of this overview and can be reviewed in the original article. Different types of T Cells, a major immune cell group coordinating our immune system, are also affected by resveratrol.
Some, like Th17 are downregulated and thus suppress the inflammation caused by these Th17 cells. Others, like Treg, which control inflammation appear to be activated. This seems to improve the control of inflammation. Several experimental models of autoimmune disease are descried in the original article which demonstrate that at least in these lab conditions, resveratrol can lower the damage caused by such autoimmunity.
In particular, resveratrol appears to reduce the adverse effects of obesity on immune function, possibly through lowering blood sugar levels slightly.
It also appears to upregulate a major anti-inflammatory pathway called nuclear factor erythroid 2-related factor 2 Nrf2. A final mechanism by which resveratrol appears to improve immune function comes through its ability to boost Natural Killer NK cell function. These immune cells fight against viral infections and the growth of cancer cells in our bodies.
Improving their function has obvious implications for a number of health conditions. Interestingly, this benefit appears greater at lower concentrations of resveratrol. With this overview, one can see the great potential for resveratrol in the treatment of multiple human diseases.
Actual studies of resveratrol in real clinical studies has been more mixed. Its wide variety of effects, differing effects at different concentrations, and its poor bioavailability when taken orally have complicated these studies.
In our clinic we utilize it with success for a number of immune and non-immune conditions. Even if you prefer to avoid another capsule, including food sources is likely a good idea as we await further studies.
Helping our patients live healthier more abundant lives requires continued study of continued research while we continually apply all we know to the patient sitting before us daily in the office.
Malaguarnera, Lucia. Sanctuary Functional Medicine, under the direction of Dr Eric Potter, IFMCP MD, provides functional medicine services to Nashville, Middle Tennessee and beyond.
We frequently treat patients from Kentucky, Alabama, Mississippi, Georgia, Ohio, Indiana, and more offering the hope of healthier more abundant lives to those with chronic illness. Your email address will not be published. Save my name, email, and website in this browser for the next time I comment.
Post comment. Resveratrol has specifically been shown to increase levels of important immune cells including gamma delta T cells, macrophage-derived chemokine MDC , and interleukin IL These benefits can be achieved by supplementing with 1, mg daily of resveratrol.
Cision PR Newswire. Mar 03, Micronutrient Information Center. Linus Pauling Institute, Oregon State University, Corvallis, OR; Biological Effects of Resveratrol. Life Sci. Vascular dysfunction in aging: potential effects of resveratrol, an anti-inflammatory phytoestrogen.
Current medicinal chemistry ; 13 9 Mechanism of human SIRT1 activation by resveratrol. J Biol Chem. Resveratrol and Immune Cells: A Link to Improve Human Health.
Influence of Resveratrol on the Immune Response. The Repeated Administration of Resveratrol Has Measurable Effects on Circulating T-Cell Subsets in Humans.
Oxid Med Cell Longev. Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer's disease. J Neuroinflammation. Blog Resveratrol: An Immune System Supplement for Overall Health There are many supplements on the market to help support immune health, and there's one gaining popularity.
By By Gene Bruno, MS, MHS, RH AHG. By Gene Bruno, MS, MHS, RH AHG Not surprisingly, over the past few years, there has been significant interest in dietary supplements for immune health. Resveratrol Background Resveratrol is a type of natural phenol produced by several plants in response to injury or attack by pathogens.
While the Resveratrol and immune system literally of Natural body cleanse movies battles for our attention, Chitosan for dental health should instead consider real-life heroes anv the world of natural therapies. Movie amd Resveratrol and immune system get the Natural body cleanse going ijmune a day or Resverafrol, but natural heroes Rseveratrol resveratrol can offer far more benefits to our health. We could extol resveratrol for a variety of health arenas like cardiovascular, brain health, and longevity, but its immune supporting powers are what really deserve attention here. This natural polyphenol offers itself for consumption not only in a supplement capsule, but also in red wine, many red grapes, blueberries, rhubarb, and oddly enough, peanuts. Both the natural and the supplement forms offer benefits for a variety of autoimmune and chronic inflammatory conditions. Visit browsehappy. We are Resverztrol aware Rseveratrol our immune system plays a crucial role in keeping us healthy. Lately, immuhe has Muscle building rest periods a hot topic Resveratrol and immune system every news channel and Resveratorl media feed. The topic of viral infection and particularly the spread of coronavirus COVIDhas gained so much attention that a person can hardly avoid being bombarded by the news of this serious situation in many countries. One point brought to our attention is the need for maintaining a well-balanced immune system to fight viral and bacterial infections.
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