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Just basic info, there is tons out there. ill update with interesting info as we go.
[ame="http://en.wikipedia.org/wiki/Resveratrol"]Resveratrol - Wikipedia, the free encyclopedia[/ame]
info on vision and eye health
resveratrol stops out-of-control blood vessel growth (angiogenesis) in the eye(via SIR2),other benefits cuz NO,Ca+,potassium channels,dilation,antiapoptosis etc etc :
age or smoke related retinal pigment epithelial degeneration-http://www.ncbi.nlm.nih.gov/pubmed/20565308
Resveratrol protects human retinal pigment epithelial cells from acrolein-induced damage.
Sheu SJ, Liu NC, Chen JL.
Department of Ophthalmology, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan. [email protected]
Abstract
PURPOSE: Although the exact pathogenesis of age-related macular degeneration (AMD) is not clear, most studies indicate a role for retinal pigment epithelial (RPE) cell damage and death caused by oxidative stress. The purpose of this study was to examine the potential protective effects of lutein, zeaxanthin, meclofenamic acid, and resveratrol on the acrolein-induced oxidative stress in human RPE cells.
METHODS: Cultured human RPE R-50 cells were treated with acrolein at different concentrations and treatment times. The protective effects of lutein (100 microM), zeaxanthin (100 microM), meclofenamic acid (30 microM), and resveratrol (10 microM) were investigated by pretreatment with the above agents before toxicant exposure in acute toxicity models and cotreatment with the toxicant in chronic toxicity models. The synergistic effects of acrolein and hydrogen peroxide exposure were also studied. Fluorescent latex beads were used to assess the phagocytic function of the cells.
RESULTS: Acrolein inhibited the phagocytic function of human RPE R-50 cells, and the inhibitory effects were time dependent. Pretreatment with lutein, zeaxanthin, meclofenamic acid, or resveratrol alleviated the inhibition of phagocytosis in the acute acrolein and combined acrolein/hydrogen peroxide toxicity models. Synergistic effects were seen between zeaxanthin and resveratrol or meclofenamic acid. Cotreatment with lutein, zeaxanthin, meclofenamic acid, or resveratrol showed a protective effect against the damage caused by 7-day acrolein exposure followed by hydrogen peroxide treatment.
CONCLUSIONS: Our results indicated an inhibitory effect of compounds found in cigarette smoke on human RPE phagocytosis, and lutein, zeaxanthin, meclofenamic acid, and resveratrol each offered protection against this inhibition. Therefore, red wine polyphenol, resveratrol, might ameliorate acrolein-induced or age-related RPE degeneration, such as AMD.
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Prevention of ocular inflammation ... [Invest Ophthalmol Vis Sci. 2009] - PubMed - NCBI
Invest Ophthalmol Vis Sci. 2009 Jul;50(7):3512-9. Epub 2009 Mar 11.
Prevention of ocular inflammation in endotoxin-induced uveitis with resveratrol by inhibiting oxidative damage and nuclear factor-kappaB activation.
Kubota S, Kurihara T, Mochimaru H, Satofuka S, Noda K, Ozawa Y, Oike Y, Ishida S, Tsubota K.
Department ofOphthalmology, Laboratory of Retinal Cell Biology, Keio University School of Medicine, Tokyo, Japan.
Abstract
PURPOSE: Resveratrol is known as one of the antioxidant polyphenols contained in red wine and grape skin. The purpose of the present study was to investigate the role of resveratrol in ocular inflammation in endotoxin-induced uveitis (EIU).
METHODS: EIU was induced in male C57/B6 mice at the age of 6 weeks by a single intraperitoneal injection of lipopolysaccharide (LPS). Animals had received oral supplementation of resveratrol at the doses of 5, 50, 100, or 200 mg/kg for 5 days until LPS injection. Twenty-four hours after LPS administration, leukocyte adhesion to the retinal vasculature was examined with a concanavalin A lectin perfusion-labeling technique. Retinal and retinal pigment epithelium (RPE)-choroidal levels of intercellular adhesion molecule (ICAM)-1, monocyte chemotactic protein (MCP)-1, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nuclear translocation of nuclear factor (NF)-kappaB p65 were evaluated by enzyme-linked immunosorbent assay. Retinal and RPE-choroidal activities of silent information regulator two ortholog (SIRT) 1 were measured by deacetylase fluorometric assay.
RESULTS: Resveratrol pretreatment led to significant and dose-dependent suppression of leukocyte adhesion to retinal vessels of EIU mice compared with vehicle application. Protein levels of MCP-1 and ICAM-1 in the retina and the RPE-choroid of EIU animals were significantly reduced by resveratrol administration. Importantly, resveratrol-treated animals showed significant decline of retinal 8-OHdG generation and nuclear NF-kappaB P65 translocation, both of which were upregulated after EIU induction. RPE-choroidal SIRT1 activity, reduced in EIU animals, was significantly augmented by treatment with resveratrol.
CONCLUSIONS: Resveratrol prevented EIU-associated cellular and molecular inflammatory responses by inhibiting oxidative damage and redox-sensitive NF-kappaB activation.
PMID: 19279313 [PubMed - indexed for MEDLINE]Free Article
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Resveratrol and large-conductance calc... [J Ocul Pharmacol Ther. 2008] - PubMed - NCBI
Resveratrol and large-conductance calcium-activated potassium channels in the protection of human retinal pigment epithelial cells.
Sheu SJ, Bee YS, Chen CH.
School of Medicine, National Yang-Ming University, Taipei, Taiwan. [email protected]
Abstract
This study was undertaken to examine the possible association of large-conductance calcium-activated potassium channels (BK(Ca) channels) and human retinal pigment epithelial (RPE) R-50 cell phagocytosis. The potential antioxidative effect of resveratrol in human RPE cells also was investigated. Cultured human RPE R-50cells were treated with hydrogen peroxide ( H(2)O(2), 10 microM, 20 min), meclofenamic acid (30 microM, 20 min), paxilline (100 nM, 20 min), or resveratrol (10 microM, 20 min), respectively. Meclofenamic acid (30 microM, 20 min) or resveratrol (10 microM, 20 min) was given after exposure to H(2)O(2) . Pretreatment with meclofenamic acid, resveratrol, or paxilline before H(2)O(2) exposure also was performed. Fluorescent latex beads then were fed for 4 h, and phagocytic function was assessed by flow cytometry. H(2)O(2) inhibited the phagocytic function of human RPE R-50 cells. The BK(Ca) channel inhibitor, paxilline, inhibited RPE phagocytosis, as did hyperoxide stress. The BK(Ca) channel opener, meclofenamic acid, prevented the damage caused by H(2)O(2) . Pretreatment with resveratrol also provided protection against damage caused by H(2)O(2) . However, further treatment with resveratrol or meclofenamic acid was not found to offer protection from H(2)O(2) exposure. In conclusion, the dietary antioxidant, resveratrol, significantly reduced oxidative damage on phagocytic function in human RPE R-50 cells. One of the underlying mechanisms might be linked to the activity of BK(Ca) channels in RPE cells.
PMID: 19049310 [PubMed - indexed for MEDLINE]
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Resveratrol prevents antibody-induced apoptoti... [BMC Res Notes. 2008] - PubMed - NCBI
BMC Res Notes. 2008 Dec 1;1:122.
Resveratrol prevents antibody-induced apoptotic death of retinal cells through upregulation of Sirt1 and Ku70.
Anekonda TS, Adamus G.
Department of Ophthalmology, Casey Eye Institute, School of Medicine, Oregon Health & Science University, Portland, Oregon 97239, USA. [email protected].
Abstract
ABSTRACT:
BACKGROUND: To determine whether resveratrol, a natural plant-derived drug, has protective effects against antibody-induced apoptosis of retinal cells in vitro and to provide insights on the mechanism of resveratrol protection.
FINDINGS: E1A.NR3 retinal cells pretreated with 40 muM resveratrol were grown in the presence of anti-recoverin (Rec-1), anti-enolase (Enol-1) antibodies, and normal purified immunoglobulins. When the cells were exposed to resveratrol before treatment with Enol-1 or Rec-1 antibodies, 30-55% more cells survived compared to the resveratrol-untreated cells. Western blotting showed a reduction in proapoptotic protein Bax in the cytoplasm and mitochondria of resveratrol-treated cells. Resveratrol-pretreated cells also showed a significant decrease in intracellular calcium and an inhibition of caspase-3 activity as compared to the untreated cells. Sirt1 expression was greatly reduced in the cells grown in the presence of Rec-1 and Enol-1, but it increased about five times in the resveratrol-pretreated cells. Immunocytochemistry revealed that Sirt1 expression in the cytoplasm and nucleus was colocalized with Ku70 expression in resveratrol-treated cells, suggesting possible interaction with each other in the cell. The pattern of the Ku70 cellular localization also overlapped with the Bax cellular localization in treated and untreated cells.
CONCLUSION: In vitro protection of retinal cells from apoptosis by resveratrol occurred through multiple early molecular events, such as reduction of intracellular calcium levels, down-regulation of Bax, up-regulation of Sirt1 and Ku70 activities, and inhibition of caspase-3 activity. These findings will help designing future in vivo and pre-clinical treatments for autoimmune retinopathies.
PMID: 19046449 [PubMed - in process]PMCID: PMC2633309Free PMC Article
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Resveratrol prevents the expression of gla... [Food Chem Toxicol. 2009] - PubMed - NCBI
Resveratrol prevents the expression of glaucoma markers induced by chronic oxidative stress in trabecular meshwork cells.
Luna C, Li G, Liton PB, Qiu J, Epstein DL, Challa P, Gonzalez P.
Duke Eye Center, Duke University Medical Center, Box 3802, Durham, NC 27710, USA.
Abstract
Elevated intraocular pressure (IOP) constitutes the best characterized risk for primary open-angle glaucoma (POAG). Elevated IOP is believed to result from an increase in aqueous humor outflow resistance at the level of the trabecular meshwork (TM)/Schlemm's canal. Malfunction of the TM in POAG is associated with the expression of markers for inflammation, cellular senescence, oxidative damage, and decreased cellularity. Current POAG treatments rely on lowering IOP, but there is no therapeutic approach available to delay the loss of function of the TM in POAG patients. We evaluated the effects of chronic administration of the dietary supplement resveratrol on the expression of markers for inflammation, oxidative damage, and cellular senescence in primary TM cells subjected to chronic oxidative stress (40% O2). Resveratrol treatment effectively prevented increased production of intracellular reactive oxygen species (iROS) and inflammatory markers (IL1alpha, IL6, IL8, and ELAM-1), and reduced expression of the senescence markers sa-beta-gal, lipofuscin, and accumulation of carbonylated proteins. Furthermore, resveratrol exerted antiapoptotic effects that were not associated with a decrease in cell proliferation. These results suggest that resveratrol could potentially have a role in preventing the TM tissue abnormalities observed in POAG.
PMID: 19027816 [PubMed - indexed for MEDLINE]PMCID: PMC2674270Free PMC Article
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Phytochemicals and age-related eye diseases. [Nutr Rev. 2008] - PubMed - NCBI
Nutr Rev. 2008 Aug;66
465-72.
Phytochemicals and age-related eye diseases.
Rhone M, Basu A.
Department of Nutritional Sciences, Oklahoma State University, Stillwater, Oklahoma 74078-6141, USA.
Abstract
Cataracts, glaucoma, and age-related macular degeneration (AMD) are common causes of blindness in the elderly population of the United States. Additional risk factors include obesity, smoking, and inadequate antioxidant status. Phytochemicals, as antioxidants and anti-inflammatory agents, may help prevent or delay the progression of these eye diseases. Observational and clinical trials support the safety of higher intakes of the phytochemicals lutein and zeaxanthin and their association with reducing risks of cataracts in healthy postmenopausal women and improving clinical features of AMD in patients. Additional phytochemicals of emerging interest, like green tea catechins, anthocyanins, resveratrol, and Ginkgo biloba, shown to ameliorate ocular oxidative stress, deserve more attention in future clinical trials.
PMID: 18667008 [PubMed - indexed for MEDLINE]
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grape seed+resv on lens-
Effect of grape polyphenols on oxidative stress... [Am J Vet Res. 2008] - PubMed - NCBI
Am J Vet Res. 2008 Jan;69(1):94-100.
Effect of grape polyphenols on oxidative stress in canine lens epithelial cells.
Barden CA, Chandler HL, Lu P, Bomser JA, Colitz CM.
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
Abstract
OBJECTIVE: To evaluate whether the effects of oxidative stress could be attenuated in cultures of canine lens epithelial cells (LECs) by incubation with grape seed proanthocyanidin extract (GSE), resveratrol (RES), or a combination of both (GSE+RES).
SAMPLE POPULATION: Primary cultures of canine LECs.
PROCEDURES: LECs were exposed to 100MM tertiary butyl-hydroperoxide (TBHP) with or without GSE, RES, or GSE+RES. The dichlorofluorescein assay was used to detect production of reactive oxygen species (ROS), and immunoblot analysis was used to evaluate the expression of stress-induced cell-signaling markers (ie, the mitogen-activated protein kinase [MAPK] and phosphoinositide-3 kinase [PI3K] pathways).
RESULTS: GSE and GSE+RES significantly reduced ROS production after a 30-minute exposure to TBHP. Only GSE significantly reduced ROS production after a 120-minute exposure to TBHP. Incubation with GSE reduced TBHP-induced activity of the MAPK and PI3K pathways.
CONCLUSIONS AND CLINICAL RELEVANCE: GSE inhibited key components associated with cataractogenesis, ROS production, and stress-induced cell signaling. On the basis of the data reported here, there is strong evidence that GSE could potentially protect LECs from the damaging effects of oxidative stress.
PMID: 18167093 [PubMed - indexed for MEDLINE]
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Resveratrol, a component of red wi... [Invest Ophthalmol Vis Sci. 2007] - PubMed - NCBI
Invest Ophthalmol Vis Sci. 2007 Sep;48(9):4232-9.
Resveratrol, a component of red wine, elicits dilation of isolated porcine retinal arterioles: role of nitric oxide and potassium channels.
Nagaoka T, Hein TW, Yoshida A, Kuo L.
Department of Ophthalmology, Scott & White Eye Institute, College of Medicine, Texas A&M Health Science Center, Temple, TX 76504, USA. [email protected]
Abstract
PURPOSE: Resveratrol, a polyphenolic phytoalexin found in grapes and red wine, has been shown to exert cardiovascular benefits, but its action in the retinal microcirculation remains unknown. In this study, the direct effect and the underlying mechanism of the vasomotor action of resveratrol were examined in retinal arterioles.
METHODS: Porcine retinal arterioles were isolated, cannulated, and pressurized without flow for in vitro study. Resveratrol-induced diameter changes were recorded by videomicroscopic techniques.
RESULTS: Retinal arterioles (65 +/- 3 microm) dilated dose dependently in response to resveratrol (1-50 microM). The removal of the endothelium reduced this dilation by 50%. Inhibition of nitric oxide (NO) synthase (by L-NAME; N(G)-nitro-L-arginine methyl ester) and blockade of soluble guanylyl cyclase (by ODQ; 1H-1,2,4-oxadiazolo[4,3-a]quinoxalin-1-one) produced similar inhibition as that produced by denudation. However, the resveratrol response was not affected by indomethacin (a cyclooxygenase inhibitor) and sulfaphenazole (an epoxygenase inhibitor). Intraluminal administration of an extracellular signal-regulated kinase (ERK) inhibitor (PD98059), but not an estrogen receptor blocker (ICI 182780), also reduced vasodilation by 50%. A nonselective K(+) channel blocker, tetraethylammonium (TEA), and a large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel inhibitor, iberiotoxin, produced identical inhibition of resveratrol-induced dilation. However, the dilation was insensitive to the inhibitors of ATP-sensitive K(+) channels and voltage-gated K(+) channels. Coadministration of L-NAME and iberiotoxin almost abolished the vasodilation induced by resveratrol.
CONCLUSIONS: Resveratrol elicits endothelium-dependent and -independent dilation of retinal arterioles. Endothelium-dependent dilation is mediated by the released NO, probably via NO synthase (NOS) activation by the ERK pathway and the subsequent activation of soluble guanylyl cyclase. The activation of BK(Ca) channels in smooth muscle contributes to the endothelium-independent dilation caused by resveratrol. A better understanding of the action of resveratrol on retinal vasculature may help shed light on its therapeutic potential for retinal vascular disease.
PMID: 17724212 [PubMed - indexed for MEDLINE]Free Article
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SIRT1 activation confers neuroprot... [Invest Ophthalmol Vis Sci. 2007] - PubMed - NCBI
Invest Ophthalmol Vis Sci. 2007 Aug;483602-9.
SIRT1 activation confers neuroprotection in experimental optic neuritis.
Shindler KS, Ventura E, Rex TS, Elliott P, Rostami A.
F.M. Kirby Center for Molecular Ophthalmology, Department of Ophthalmology, University of Pennsylvania Scheie Eye Institute, Philadelphia, Pennsylvania 19104, USA. [email protected]
Abstract
PURPOSE: Axonal damage and loss of neurons correlate with permanent vision loss and neurologic disability in patients with optic neuritis and multiple sclerosis (MS). Current therapies involve immunomodulation, with limited effects on neuronal damage. The authors examined potential neuroprotective effects in optic neuritis by SRT647 and SRT501, two structurally and mechanistically distinct activators of SIRT1, an enzyme involved in cellular stress resistance and survival.
METHODS: Experimental autoimmune encephalomyelitis (EAE), an animal model of MS, was induced by immunization with proteolipid protein peptide in SJL/J mice. Optic neuritis developed in two thirds of eyes with significant retinal ganglion cell (RGC) loss detected 14 days after immunization. RGCs were labeled in a retrograde fashion with fluorogold by injection into superior colliculi. Optic neuritis was detected by inflammatory cell infiltration of the optic nerve.
RESULTS: Intravitreal injection of SIRT1 activators 0, 3, 7, and 11 days after immunization significantly attenuated RGC loss in a dose-dependent manner. This neuroprotective effect was blocked by sirtinol, a SIRT1 inhibitor. Treatment with either SIRT1 activator did not prevent EAE or optic nerve inflammation. A single dose of SRT501 on day 11 was sufficient to limit RGC loss and to preserve axon function.
CONCLUSIONS: SIRT1 activators provide an important potential therapy to prevent the neuronal damage that leads to permanent neurologic disability in optic neuritis and MS patients. Intravitreal administration of SIRT1 activators does not suppress inflammation in this model, suggesting that their neuroprotective effects will be additive or synergistic with current immunomodulatory therapies.
PMID: 17652729 [PubMed - indexed for MEDLINE]PMCID: PMC1964753Free PMC
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The effect of resveratrol in experimental catar... [Curr Eye Res. 2006] - PubMed - NCBI
Curr Eye Res. 2006 Feb;31(2):147-53.
The effect of resveratrol in experimental cataract model formed by sodium selenite.
Doganay S, Borazan M, Iraz M, Cigremis Y.
Department of Ophthalmology, Inonu University Medical Faculty, Turgut Ozal Medical Center, Malatya, Turkey. sdoganay2inonu.edu.tr
Abstract
PURPOSE: To investigate if resveratrol can prevent sodium selenite-induced experimental cataract model in rats.
METHODS: Forty-eight Spraque-Dawley rat pups were divided into 3 treatment groups: (1) normal saline-% 5 ethanol injected i.p. on postpatum day 10; (2) Na selenite (30 nmol/g body wt) injected s.c on day 10; (3) Na selenite s.c on day 10+resveratrol (40 mg/kg) i.p on days 10-13. On day 21, cataract development was graded by slit-lamp examination and photography. Encapsulated lenses and erythrocytes were analyzed for reduced glutathione (GSH) and malondialdehyde (MDA), a marker of lipid peroxidation. Lenses were also analyzed for total nitrite (TN).
RESULTS: All control lenses in group 1 were clear. In group 2, all rats developed cataracts (grade 3-grade 6), whereas in group 3, only 9 of 16 rats developed cataracts (grade 2-grade 3). The difference of cataract frequency between groups 2 and 3 was statistically significant (p<0.05). Group 3 lenses and erythrocytes had higher mean GSH and lower mean MDA levels than those in group 2 (p<0.05). TN was highest in group 3 and lowest in group 1 (p<0.05).
CONCLUSIONS: Resveratrol suppressed selenite-induced oxidative stress and cataract formation in rats. This protective effect was supported by higher GSH and lower MDA in lens and erythrocytes. The presence of oxidative stress in selenite cataract development and its prevention by resveratrol support the possibility that high natural consumption of resveratrol in food can help prevent human senile cataract.
PMID: 16500765 [PubMed - indexed for MEDLINE]
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Resveratrol reduces oxidation and prolife... [Chem Biol Interact. 2005] - PubMed - NCBI
Chem Biol Interact. 2005 Jan 15;151(2):143-9.
Resveratrol reduces oxidation and proliferation of human retinal pigment epithelial cells via extracellular signal-regulated kinase inhibition.
King RE, Kent KD, Bomser JA.
Department of Food Science and Technology, Ohio State University, 1787 Neil Ave., Columbus, OH 43210, USA.
Abstract
Epidemiological evidence suggests that moderate wine consumption and antioxidant-rich diets may protect against age-related macular degeneration (AMD), the leading cause of vision loss among the elderly. Development of AMD and other retinal diseases, such as proliferative vitreoretinopathy (PVR), is associated with oxidative stress in the retinal pigment epithelium (RPE), a cell layer responsible for maintaining the health of the retina by providing structural and nutritional support. We hypothesize that resveratrol, a red wine polyphenol, may be responsible, in part, for the health benefits of moderate red wine consumption on retinal disease. To test this hypothesis, the antioxidant and antiproliferative effects of resveratrol were examined in a human RPE cell line (designated ARPE-19). Cell proliferation was determined using the bromodeoxyuridine (BrdU) assay, intracellular oxidation was assessed by dichlorofluorescein fluorescence, and activation of the mitogen-activated protein kinase (MAPK) cascade was measured by immunoblotting. Treatment with 50 and 100 micromol/L resveratrol significantly reduced proliferation of RPE cells by 10% and 25%, respectively (P<0.05). This reduction in proliferation was not associated with resveratrol-induced cytotoxicity. Resveratrol (100 micromol/L) inhibited basal and H2O2-induced intracellular oxidation and protected RPE cells from H2O2-induced cell death. The observed reduction in cell proliferation was associated with inhibition of mitogen activated protein kinase/ERK (MEK) and extracellular signal-regulated kinase (ERK 1/2) activities at concentrations of resveratrol as low as 5 micromol/L. These results suggest that resveratrol can reduce oxidative stress and hyperproliferation of the RPE.
PMID: 15698585 [PubMed - indexed for MEDLINE]
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Resveratrol inhibits neuronal apoptosis and elevate... [Diabetes. 2010] - PubMed - NCBI
Resveratrol inhibits neuronal apoptosis and elevated Ca2+/calmodulin-dependent protein kinase II activity in diabetic mouse retina.
Kim YH, Kim YS, Kang SS, Cho GJ, Choi WS.
Department of Anatomy and Neurobiology, Gyeongsang National University, Jinju, Gyeongnam, Korea.
Abstract
OBJECTIVE: This study investigated the effects of resveratrol, a natural polyphenol with neuroprotective properties, on retinal neuronal cell death mediated by diabetes-induced activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII).
RESEARCH DESIGN AND METHODS: Diabetes was induced in C57BL/6 mice by five consecutive intraperitoneal injections of 55 mg/kg streptozotocin (STZ). Control mice received buffer. All mice were killed 2 months after the injections, and the extent of neuronal cell death, CaMKII, and phospho-CaMKII protein expression levels and CaMKII kinase activity were examined in the retinas. To assess the role of CaMKII in the death of retinal neurons, a small-interfering RNA (siRNA) or specific inhibitor of CaMKII was injected into the right vitreous humor, and vehicle only was injected into the left vitreous humor, 2 days before death. Resveratrol (20 mg/kg) was administered by oral gavage daily for 4 weeks, beginning 1 month after the fifth injection of either STZ or buffer.
RESULTS: The death of retinal ganglion cells (RGCs), CaMKII, phospho-CaMKII protein levels, and CaMKII activity were all greatly increased in the retinas of diabetic mice compared with controls, 2 months after induction of diabetes. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL)-positive signals co-localized with CaMKII- and phospho-CaMKII immunoreactive RGCs. However, in addition to CaMKII knockdown and inhibition by siRNA or a specific inhibitor, respectively, resveratrol provided complete protection from diabetes-induced retinal cell death.
CONCLUSIONS: In the present study, resveratrol prevented diabetes-induced RGC death via CaMKII downregulation, implying that resveratrol may have potential therapeutic applications for prevention of diabetes-induced visual dysfunction
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Retinal protective effects of resveratro... [Korean J Ophthalmol. 2010] - PubMed - NCBI
Korean J Ophthalmol. 2010 Apr;24(2):108-18. Epub 2010 Apr 6.
Retinal protective effects of resveratrol via modulation of nitric oxide synthase on oxygen-induced retinopathy.
Kim WT, Suh ES.
Department of Pediatrics, Catholic University of Daegu School of Medicine, Daegu, Korea.
Abstract
PURPOSE: Retinopathy of prematurity (ROP) is one of the leading causes of blindness, with retinal detachment occurring due to oxygen toxicity in preterm infants. Recently, advances in neonatal care have led to improved survival rates for preterm infants, and ROP has increased in incidence. In the present study, we aimed to determine whether or not resveratrol exhibits protective effects in an animal model of ROP and in primary retinal cell cultures of neonatal rat via nitric oxide (NO)-modulating actions using western blotting and real-time PCR with inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS) and neuronal NOS (nNOS) antibodies and mRNAs.
METHODS: In an in vivo oxygen-induced retinopathy (OIR) model, cyclic hyperoxia was induced with 80% O(2) for one day and 21% O(2) for one day from P1 to P14 in newborn Sprague-Dawley (SD) rats. Resveratrol was injected intravitreally for seven days and rats were sacrificed at P21. In vitro OIR primary retinal cell culture was performed using P0-2 SD rats. Hyperoxia injuries were induced through 100% O(2) exposure for six hours. Western blotting and real-time PCR using iNOS, eNOS, nNOS antibodies and primers were performed in the rat model of ROP and the dispersed retinal cell culture.
RESULTS: In both in vivo and in vitro OIR, the expression of iNOS antibody and mRNA was increased and of eNOS and nNOS were reduced in the resveratrol-treated group.
CONCLUSIONS: In conclusion, resveratrol appeared to exert retinal protective effects via modulation of NO-mediated mechanism in in vivo and in vitro OIR models.
PMID: 20379461 [PubMed - indexed for MEDLINE]PMCID: PMC2850998Free PMC Article
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Inhibition of apoptosis in human r... [Invest Ophthalmol Vis Sci. 2010] - PubMed - NCBI
Inhibition of apoptosis in human retinal pigment epithelial cells treated with benzo(e)pyrene, a toxic component of cigarette smoke.
Mansoor S, Gupta N, Patil AJ, Estrago-Franco MF, Ramirez C, Migon R, Sapkal A, Kuppermann BD, Kenney MC.
Department of Ophthalmology, School of Medicine, University of California, Irvine, CA 92868, USA.
Abstract
PURPOSE: To study the inhibitory effects of some agents or drugs (inhibitors) on benzo(e)pyrene (B(e)P)-induced cell death and apoptosis on human retinal pigment epithelial (ARPE-19) cells in vitro.
METHODS: ARPE-19 cells were pretreated with varying concentrations of different classes of inhibitors (calpain, benzyl isothiocyanate [BITC], simvastatin, epicatechin, genistein, resveratrol, and memantine) before B(e)P exposure. Cell viability (CV) was determined by a trypan blue dye-exclusion assay. Caspase-3/7 and caspase-9 activities were measured by fluorochrome assays. The production of reactive oxygen/nitrogen species (ROS/RNS) was measured with 2',7'-dicholorodihydrofluorescein diacetate dye assay.
RESULTS: At 30-microM concentrations, the genistein, resveratrol, and memantine inhibitors were able to reverse significantly the loss of cell viability, the activation of caspase-3/7 and caspase-9, and the production of ROS/RNS in ARPE-19 cell cultures. Memantine was the most potent and genistein was the least effective inhibitor in blocking the B(e)P-induced effects. Calpain, BITC, simvastatin, and epicatechin did not reverse the loss of cell viability in B(e)P-treated ARPE-19 cells. As a matter of fact, at the concentrations studied (15, 30, 45 microM), the BITC plus B(e)P-treated cultures showed significantly lower cell viability than the B(e)P-treated culture alone, suggesting BITC-related toxicity.
CONCLUSIONS: Genistein, resveratrol, and memantine can reverse the apoptosis and oxidant production generated by B(e)P, a toxic element of smoking. These inhibitors may be beneficial against retinal diseases associated with the loss of RPE cells.
PMID: 19959636 [PubMed - indexed for MEDLINE]
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"""In addition, these results have uncovered a sirtuin-independent pathway by which resveratrol regulates angiogenesis."""
Resveratrol regulates pathologic angiogenesis by... [Am J Pathol. 2010] - PubMed - NCBI
Am J Pathol. 2010 Jul;177(1):481-92. Epub 2010 May 14.
Resveratrol regulates pathologic angiogenesis by a eukaryotic elongation factor-2 kinase-regulated pathway.
Khan AA, Dace DS, Ryazanov AG, Kelly J, Apte RS.
Departments of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, USA.
Abstract
Abnormal angiogenesis is central to the pathophysiology of diverse disease processes including cancers, ischemic and atherosclerotic heart disease, and visually debilitating eye disease. Resveratrol is a naturally occurring phytoalexin that has been demonstrated to ameliorate and decelerate the aging process as well as blunt end organ damage from obesity. These effects of resveratrol are largely mediated by members of the sirtuin family of proteins. We demonstrate that resveratrol can inhibit pathological angiogenesis in vivo and in vitro by a sirtuin-independent pathway. Resveratrol inhibits the proliferation and migration of vascular endothelial cells by activating eukaryotic elongation factor-2 kinase. The active kinase in turn phosphorylates and inactivates elongation factor-2, a key mediator of ribosomal transfer and protein translation. Functional inhibition of the kinase by gene deletion in vivo or RNA as well as pharmacological inhibition in vitro is able to completely reverse the effects of resveratrol on blood vessel growth. These studies have identified a novel and critical pathway that promotes aberrant vascular proliferation and one that is amenable to modulation by pharmacological means. In addition, these results have uncovered a sirtuin-independent pathway by which resveratrol regulates angiogenesis.
resveratrol tetramer: Vaticanol C, a resveratrol tetramer, activ... [Nutr Metab (Lond). 2010] - PubMed - NCBI
lymph node and lung methastasis Vaticanol C, a novel resveratrol ... [Cancer Chemother Pharmacol. 2007] - PubMed - NCBI
Quote:
Vaticanol C, a resveratrol tetramer, activates PPARalpha and PPARbeta/delta in vitro and in vivo.
Tsukamoto T, Nakata R, Tamura E, Kosuge Y, Kariya A, Katsukawa M, Mishima S, Ito T, Iinuma M, Akao Y, Nozawa Y, Arai Y, Namura S, Inoue H.
Department of Food Science and Nutrition, Nara Women's University, Nara, 630-8506, Japan. [email protected].
Abstract
ABSTRACT:
BACKGROUND: Appropriate long-term drinking of red wine is associated with a reduced risk of cardiovascular disease. Resveratrol, a well-known SIRT1 activator is considered to be one of the beneficial components contained in red wine, and also developed as a drug candidate. We previously demonstrated that resveratrol protects brain against ischemic stroke in mice through a PPARalpha-dependent mechanism. Here we report the different effects of the oligomers of resveratrol.
METHODS: We evaluated the activation of PPARs by epsilon-viniferin, a resveratrol dimer, and vaticanol C, a resveratrol tetramer, in cell-based reporter assays using bovine arterial endothelial cells, as well as the activation of SIRT1. Moreover, we tested the metabolic action by administering vaticanol C with the high fat diet to wild-type and PPARalpha-knockout male mice for eight weeks.
RESULTS: We show that vaticanol C activates PPARalpha and PPARbeta/delta in cell-based reporter assays, but does not activate SIRT1. epsilon-Viniferin shows a similar radical scavenging activity as resveratrol, but neither effects on PPARs and SIRT-1. Eight-week intake of vaticanol C with a high fat diet upregulates hepatic expression of PPARalpha-responsive genes such as cyp4a10, cyp4a14 and FABP1, and skeletal muscle expression of PPARbeta/delta-responsive genes, such as UCP3 and PDK4 (pyruvate dehydrogenase kinase, isoform 4), in wild-type, but not PPARalpha-knockout mice.
CONCLUSION: Vaticanol C, a resveratrol tetramer, activated PPARalpha and PPARbeta/delta in vitro and in vivo. These findings indicate that activation of PPARalpha and PPARbeta/delta by vaticanol C may be a novel mechanism, affording beneficial effects against lifestyle-related diseases.
PMID: 20504373 [PubMed - in process]PMCID: PMC2882917Free PMC Article
Quote:
Vaticanol C, a novel resveratrol tetramer, reduces lymph node and lung metastases of mouse mammary carcinoma carrying p53 mutation.
Shibata MA, Akao Y, Shibata E, Nozawa Y, Ito T, Mishima S, Morimoto J, Otsuki Y.
Department of Anatomy and Cell Biology, Division of Basic Medicine I, Osaka Medical College, 2-7, Daigaku-machi, Takatsuki, Japan. [email protected]
Abstract
PURPOSE: The effects of vaticanol C (Vat-C), a novel resveratrol tetramer, were studied in a mouse metastatic mammary cancer model carrying mutations in p53 that produce a metastatic spectrum similar to that seen in human breast cancers.
METHODS: Mammary tumors, induced by inoculation of syngeneic BALB/c mice with BJMC3879 cells, were subsequently treated with Vat-C at 0, 100 and 200 ppm in their diet.
RESULTS: The in vitro study demonstrated that Vat-C induced apoptosis, as inferred by morphological changes, nucleosomal DNA fragmentation and elevated activities of caspases. Although tumor volumes were not apparently suppressed in mice treated with Vat-C, the multiplicity of lymph node metastasis was significantly decreased in the 200-ppm group. Furthermore, the multiplicity of lung metastasis was also significantly lower in the 200-ppm group. In any category of organ metastasis, the number of organs with metastasis tended to be lower in the 200-ppm group, but these findings were not statistically significant. The levels of apoptosis were significantly higher in the 200-ppm group, but DNA synthesis only a tended to be lower in this group. Microvessel density in tumors also tended to be lower in the Vat-C-treated groups. Moreover, the numbers of lymphatic vessels having intraluminal tumor cells was significantly lower in mammary tumors of mice given 100 and 200-ppm Vat-C, indicating a reduction in migrating tumor cells into the lymphatic vessels of tumor tissue.
CONCLUSIONS: These results suggest that the observed antimetastatic activity of Vat-C may be of clinical significance as an adjuvant therapy in metastatic human breast cancer having p53 mutations, and may also be useful as a chemopreventative of breast cancer development.
PMID: 17256131 [PubMed - indexed for MEDLINE]
activation of the apoptotic arm of the UPR and its downstream effector CHOP/GADD153 is involved, at least in part, in RES-induced apoptosis in Burkitt's lymphoma cells Updates of mTOR inhibitors. [Anticancer Agents Med Chem. 2010] - PubMed - NCBI
Resveratrol-induced p53-independent apoptosis of human nasopharyngeal carcinoma cells is correlated with the downregulation of DeltaNp63. Resveratrol-induced p53-independent apoptos... [Cancer Gene Ther. 2010] - PubMed - NCBI
so its good for asthma to? Resveratrol impairs the release of ster... [J Pharmacol Exp Ther. 2010] - PubMed - NCBI
Resveratrol protects human lens epithelial cells against H2O2-induced oxidative stress by increasing catalase, SOD-1, and HO-1 expression - Resveratrol protects human lens epithelial cells aga... [Mol Vis. 2010] - PubMed - NCBI
**broken link removed**
neuroprotective effect of resv via anti-apoptosis **broken link removed**
Anticancer Agents Med Chem. 2010 Aug 10. [Epub ahead of print]
Updates of mTOR inhibitors.
Zhou H, Luo Y, Huang S.
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA.
Abstract
Mammalian target of rapamycin (mTOR) is a central controller of cell growth, proliferation, metabolism and angiogenesis. mTOR signaling is often dysregulated in various human diseases and thus attracts great interest in developing drugs that target mTOR. Currently it is known that mTOR functions as two complexes, mTOR complex 1/2 (mTORC1/2). Rapamycin and its analogs (all termed rapalogs) first form a complex with the intracellular receptor FK506 binding protein 12 (FKBP12) and then bind a domain separated from the catalytic site of mTOR, blocking mTOR function. Rapalogs are selective for mTORC1 and effective as anticancer agents in various preclinical models. In clinical trials, rapalogs have demonstrated efficacy against certain types of cancer. Recently, a new generation of mTOR inhibitors, which compete with ATP in the catalytic site of mTOR and inhibit both mTORC1 and mTORC2 with a high degree of selectivity, have been developed. Besides, some natural products, such as epigallocatechin gallate (EGCG), caffeine, curcumin and resveratrol, have been found to inhibit mTOR as well. Here, we summarize the current findings regarding mTOR signaling pathway and review the updated data about mTOR inhibitors as anticancer agents.
That's basically what I said as the 'rapalogs' are selective for a specific mTor and cell. Hell, tea is an anti-cancer, too, and we know nothing we are taking is competing with ATP for if it was we'd feel like crap and cancer patients would be dying from mTor inhibition!
Also, clowns, with how well curcumin, tea, ECGC, and resveratrol work, there may actually be a BENEFIT to what mTor they may be inhibiting as the other mTor is obviously taking over. Seeing that tea, caffeine, and resveratrol also cause loss of FAT, that would be an obvious mTor inhibition benefit which may only affect fat cells just like IGF causes muscles to uptake glucose while causing fat cells to not.
Quote:
Rapalogs are selective for mTORC1 and effective as anticancer agents in various preclinical models. In clinical trials, rapalogs have demonstrated efficacy against certain types of cancer. Recently, a new generation of mTOR inhibitors, which compete with ATP in the catalytic site of mTOR and inhibit both mTORC1 and mTORC2 with a high degree of selectivity, have been developed
Quote:
Consistent with its role in cell proliferation, the mTOR pathway is frequently hyperactivated in a number of human malignancies and is thus considered to be an attractive target for anti-cancer therapy. Rapamycin and its analogs (rapalogs) function as allosteric inhibitors of mTORC1 and are currently used in the treatment of advanced renal cell carcinoma. Rapamycin and its derivatives bind to the small immunophilin FKBP12 to inhibit mTORC1 signalling through a poorly understood mechanism. Rapamycin/FKBP12 efficiently inhibit some, but not all, functions of mTOR and hence much interest has been placed in the development of drugs that target the kinase activity of mTOR directly. Several novel active-site inhibitors of mTOR, which inhibit both mTORC1 and mTORC2, were developed in the last year.
[ame="http://en.wikipedia.org/wiki/Resveratrol"]Resveratrol - Wikipedia, the free encyclopedia[/ame]
info on vision and eye health
resveratrol stops out-of-control blood vessel growth (angiogenesis) in the eye(via SIR2),other benefits cuz NO,Ca+,potassium channels,dilation,antiapoptosis etc etc :
age or smoke related retinal pigment epithelial degeneration-http://www.ncbi.nlm.nih.gov/pubmed/20565308
Resveratrol protects human retinal pigment epithelial cells from acrolein-induced damage.
Sheu SJ, Liu NC, Chen JL.
Department of Ophthalmology, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan. [email protected]
Abstract
PURPOSE: Although the exact pathogenesis of age-related macular degeneration (AMD) is not clear, most studies indicate a role for retinal pigment epithelial (RPE) cell damage and death caused by oxidative stress. The purpose of this study was to examine the potential protective effects of lutein, zeaxanthin, meclofenamic acid, and resveratrol on the acrolein-induced oxidative stress in human RPE cells.
METHODS: Cultured human RPE R-50 cells were treated with acrolein at different concentrations and treatment times. The protective effects of lutein (100 microM), zeaxanthin (100 microM), meclofenamic acid (30 microM), and resveratrol (10 microM) were investigated by pretreatment with the above agents before toxicant exposure in acute toxicity models and cotreatment with the toxicant in chronic toxicity models. The synergistic effects of acrolein and hydrogen peroxide exposure were also studied. Fluorescent latex beads were used to assess the phagocytic function of the cells.
RESULTS: Acrolein inhibited the phagocytic function of human RPE R-50 cells, and the inhibitory effects were time dependent. Pretreatment with lutein, zeaxanthin, meclofenamic acid, or resveratrol alleviated the inhibition of phagocytosis in the acute acrolein and combined acrolein/hydrogen peroxide toxicity models. Synergistic effects were seen between zeaxanthin and resveratrol or meclofenamic acid. Cotreatment with lutein, zeaxanthin, meclofenamic acid, or resveratrol showed a protective effect against the damage caused by 7-day acrolein exposure followed by hydrogen peroxide treatment.
CONCLUSIONS: Our results indicated an inhibitory effect of compounds found in cigarette smoke on human RPE phagocytosis, and lutein, zeaxanthin, meclofenamic acid, and resveratrol each offered protection against this inhibition. Therefore, red wine polyphenol, resveratrol, might ameliorate acrolein-induced or age-related RPE degeneration, such as AMD.
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Prevention of ocular inflammation ... [Invest Ophthalmol Vis Sci. 2009] - PubMed - NCBI
Invest Ophthalmol Vis Sci. 2009 Jul;50(7):3512-9. Epub 2009 Mar 11.
Prevention of ocular inflammation in endotoxin-induced uveitis with resveratrol by inhibiting oxidative damage and nuclear factor-kappaB activation.
Kubota S, Kurihara T, Mochimaru H, Satofuka S, Noda K, Ozawa Y, Oike Y, Ishida S, Tsubota K.
Department ofOphthalmology, Laboratory of Retinal Cell Biology, Keio University School of Medicine, Tokyo, Japan.
Abstract
PURPOSE: Resveratrol is known as one of the antioxidant polyphenols contained in red wine and grape skin. The purpose of the present study was to investigate the role of resveratrol in ocular inflammation in endotoxin-induced uveitis (EIU).
METHODS: EIU was induced in male C57/B6 mice at the age of 6 weeks by a single intraperitoneal injection of lipopolysaccharide (LPS). Animals had received oral supplementation of resveratrol at the doses of 5, 50, 100, or 200 mg/kg for 5 days until LPS injection. Twenty-four hours after LPS administration, leukocyte adhesion to the retinal vasculature was examined with a concanavalin A lectin perfusion-labeling technique. Retinal and retinal pigment epithelium (RPE)-choroidal levels of intercellular adhesion molecule (ICAM)-1, monocyte chemotactic protein (MCP)-1, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nuclear translocation of nuclear factor (NF)-kappaB p65 were evaluated by enzyme-linked immunosorbent assay. Retinal and RPE-choroidal activities of silent information regulator two ortholog (SIRT) 1 were measured by deacetylase fluorometric assay.
RESULTS: Resveratrol pretreatment led to significant and dose-dependent suppression of leukocyte adhesion to retinal vessels of EIU mice compared with vehicle application. Protein levels of MCP-1 and ICAM-1 in the retina and the RPE-choroid of EIU animals were significantly reduced by resveratrol administration. Importantly, resveratrol-treated animals showed significant decline of retinal 8-OHdG generation and nuclear NF-kappaB P65 translocation, both of which were upregulated after EIU induction. RPE-choroidal SIRT1 activity, reduced in EIU animals, was significantly augmented by treatment with resveratrol.
CONCLUSIONS: Resveratrol prevented EIU-associated cellular and molecular inflammatory responses by inhibiting oxidative damage and redox-sensitive NF-kappaB activation.
PMID: 19279313 [PubMed - indexed for MEDLINE]Free Article
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Resveratrol and large-conductance calc... [J Ocul Pharmacol Ther. 2008] - PubMed - NCBI
Resveratrol and large-conductance calcium-activated potassium channels in the protection of human retinal pigment epithelial cells.
Sheu SJ, Bee YS, Chen CH.
School of Medicine, National Yang-Ming University, Taipei, Taiwan. [email protected]
Abstract
This study was undertaken to examine the possible association of large-conductance calcium-activated potassium channels (BK(Ca) channels) and human retinal pigment epithelial (RPE) R-50 cell phagocytosis. The potential antioxidative effect of resveratrol in human RPE cells also was investigated. Cultured human RPE R-50cells were treated with hydrogen peroxide ( H(2)O(2), 10 microM, 20 min), meclofenamic acid (30 microM, 20 min), paxilline (100 nM, 20 min), or resveratrol (10 microM, 20 min), respectively. Meclofenamic acid (30 microM, 20 min) or resveratrol (10 microM, 20 min) was given after exposure to H(2)O(2) . Pretreatment with meclofenamic acid, resveratrol, or paxilline before H(2)O(2) exposure also was performed. Fluorescent latex beads then were fed for 4 h, and phagocytic function was assessed by flow cytometry. H(2)O(2) inhibited the phagocytic function of human RPE R-50 cells. The BK(Ca) channel inhibitor, paxilline, inhibited RPE phagocytosis, as did hyperoxide stress. The BK(Ca) channel opener, meclofenamic acid, prevented the damage caused by H(2)O(2) . Pretreatment with resveratrol also provided protection against damage caused by H(2)O(2) . However, further treatment with resveratrol or meclofenamic acid was not found to offer protection from H(2)O(2) exposure. In conclusion, the dietary antioxidant, resveratrol, significantly reduced oxidative damage on phagocytic function in human RPE R-50 cells. One of the underlying mechanisms might be linked to the activity of BK(Ca) channels in RPE cells.
PMID: 19049310 [PubMed - indexed for MEDLINE]
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Resveratrol prevents antibody-induced apoptoti... [BMC Res Notes. 2008] - PubMed - NCBI
BMC Res Notes. 2008 Dec 1;1:122.
Resveratrol prevents antibody-induced apoptotic death of retinal cells through upregulation of Sirt1 and Ku70.
Anekonda TS, Adamus G.
Department of Ophthalmology, Casey Eye Institute, School of Medicine, Oregon Health & Science University, Portland, Oregon 97239, USA. [email protected].
Abstract
ABSTRACT:
BACKGROUND: To determine whether resveratrol, a natural plant-derived drug, has protective effects against antibody-induced apoptosis of retinal cells in vitro and to provide insights on the mechanism of resveratrol protection.
FINDINGS: E1A.NR3 retinal cells pretreated with 40 muM resveratrol were grown in the presence of anti-recoverin (Rec-1), anti-enolase (Enol-1) antibodies, and normal purified immunoglobulins. When the cells were exposed to resveratrol before treatment with Enol-1 or Rec-1 antibodies, 30-55% more cells survived compared to the resveratrol-untreated cells. Western blotting showed a reduction in proapoptotic protein Bax in the cytoplasm and mitochondria of resveratrol-treated cells. Resveratrol-pretreated cells also showed a significant decrease in intracellular calcium and an inhibition of caspase-3 activity as compared to the untreated cells. Sirt1 expression was greatly reduced in the cells grown in the presence of Rec-1 and Enol-1, but it increased about five times in the resveratrol-pretreated cells. Immunocytochemistry revealed that Sirt1 expression in the cytoplasm and nucleus was colocalized with Ku70 expression in resveratrol-treated cells, suggesting possible interaction with each other in the cell. The pattern of the Ku70 cellular localization also overlapped with the Bax cellular localization in treated and untreated cells.
CONCLUSION: In vitro protection of retinal cells from apoptosis by resveratrol occurred through multiple early molecular events, such as reduction of intracellular calcium levels, down-regulation of Bax, up-regulation of Sirt1 and Ku70 activities, and inhibition of caspase-3 activity. These findings will help designing future in vivo and pre-clinical treatments for autoimmune retinopathies.
PMID: 19046449 [PubMed - in process]PMCID: PMC2633309Free PMC Article
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Resveratrol prevents the expression of gla... [Food Chem Toxicol. 2009] - PubMed - NCBI
Resveratrol prevents the expression of glaucoma markers induced by chronic oxidative stress in trabecular meshwork cells.
Luna C, Li G, Liton PB, Qiu J, Epstein DL, Challa P, Gonzalez P.
Duke Eye Center, Duke University Medical Center, Box 3802, Durham, NC 27710, USA.
Abstract
Elevated intraocular pressure (IOP) constitutes the best characterized risk for primary open-angle glaucoma (POAG). Elevated IOP is believed to result from an increase in aqueous humor outflow resistance at the level of the trabecular meshwork (TM)/Schlemm's canal. Malfunction of the TM in POAG is associated with the expression of markers for inflammation, cellular senescence, oxidative damage, and decreased cellularity. Current POAG treatments rely on lowering IOP, but there is no therapeutic approach available to delay the loss of function of the TM in POAG patients. We evaluated the effects of chronic administration of the dietary supplement resveratrol on the expression of markers for inflammation, oxidative damage, and cellular senescence in primary TM cells subjected to chronic oxidative stress (40% O2). Resveratrol treatment effectively prevented increased production of intracellular reactive oxygen species (iROS) and inflammatory markers (IL1alpha, IL6, IL8, and ELAM-1), and reduced expression of the senescence markers sa-beta-gal, lipofuscin, and accumulation of carbonylated proteins. Furthermore, resveratrol exerted antiapoptotic effects that were not associated with a decrease in cell proliferation. These results suggest that resveratrol could potentially have a role in preventing the TM tissue abnormalities observed in POAG.
PMID: 19027816 [PubMed - indexed for MEDLINE]PMCID: PMC2674270Free PMC Article
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Phytochemicals and age-related eye diseases. [Nutr Rev. 2008] - PubMed - NCBI
Nutr Rev. 2008 Aug;66
465-72. Phytochemicals and age-related eye diseases.
Rhone M, Basu A.
Department of Nutritional Sciences, Oklahoma State University, Stillwater, Oklahoma 74078-6141, USA.
Abstract
Cataracts, glaucoma, and age-related macular degeneration (AMD) are common causes of blindness in the elderly population of the United States. Additional risk factors include obesity, smoking, and inadequate antioxidant status. Phytochemicals, as antioxidants and anti-inflammatory agents, may help prevent or delay the progression of these eye diseases. Observational and clinical trials support the safety of higher intakes of the phytochemicals lutein and zeaxanthin and their association with reducing risks of cataracts in healthy postmenopausal women and improving clinical features of AMD in patients. Additional phytochemicals of emerging interest, like green tea catechins, anthocyanins, resveratrol, and Ginkgo biloba, shown to ameliorate ocular oxidative stress, deserve more attention in future clinical trials.
PMID: 18667008 [PubMed - indexed for MEDLINE]
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grape seed+resv on lens-
Effect of grape polyphenols on oxidative stress... [Am J Vet Res. 2008] - PubMed - NCBI
Am J Vet Res. 2008 Jan;69(1):94-100.
Effect of grape polyphenols on oxidative stress in canine lens epithelial cells.
Barden CA, Chandler HL, Lu P, Bomser JA, Colitz CM.
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
Abstract
OBJECTIVE: To evaluate whether the effects of oxidative stress could be attenuated in cultures of canine lens epithelial cells (LECs) by incubation with grape seed proanthocyanidin extract (GSE), resveratrol (RES), or a combination of both (GSE+RES).
SAMPLE POPULATION: Primary cultures of canine LECs.
PROCEDURES: LECs were exposed to 100MM tertiary butyl-hydroperoxide (TBHP) with or without GSE, RES, or GSE+RES. The dichlorofluorescein assay was used to detect production of reactive oxygen species (ROS), and immunoblot analysis was used to evaluate the expression of stress-induced cell-signaling markers (ie, the mitogen-activated protein kinase [MAPK] and phosphoinositide-3 kinase [PI3K] pathways).
RESULTS: GSE and GSE+RES significantly reduced ROS production after a 30-minute exposure to TBHP. Only GSE significantly reduced ROS production after a 120-minute exposure to TBHP. Incubation with GSE reduced TBHP-induced activity of the MAPK and PI3K pathways.
CONCLUSIONS AND CLINICAL RELEVANCE: GSE inhibited key components associated with cataractogenesis, ROS production, and stress-induced cell signaling. On the basis of the data reported here, there is strong evidence that GSE could potentially protect LECs from the damaging effects of oxidative stress.
PMID: 18167093 [PubMed - indexed for MEDLINE]
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Resveratrol, a component of red wi... [Invest Ophthalmol Vis Sci. 2007] - PubMed - NCBI
Invest Ophthalmol Vis Sci. 2007 Sep;48(9):4232-9.
Resveratrol, a component of red wine, elicits dilation of isolated porcine retinal arterioles: role of nitric oxide and potassium channels.
Nagaoka T, Hein TW, Yoshida A, Kuo L.
Department of Ophthalmology, Scott & White Eye Institute, College of Medicine, Texas A&M Health Science Center, Temple, TX 76504, USA. [email protected]
Abstract
PURPOSE: Resveratrol, a polyphenolic phytoalexin found in grapes and red wine, has been shown to exert cardiovascular benefits, but its action in the retinal microcirculation remains unknown. In this study, the direct effect and the underlying mechanism of the vasomotor action of resveratrol were examined in retinal arterioles.
METHODS: Porcine retinal arterioles were isolated, cannulated, and pressurized without flow for in vitro study. Resveratrol-induced diameter changes were recorded by videomicroscopic techniques.
RESULTS: Retinal arterioles (65 +/- 3 microm) dilated dose dependently in response to resveratrol (1-50 microM). The removal of the endothelium reduced this dilation by 50%. Inhibition of nitric oxide (NO) synthase (by L-NAME; N(G)-nitro-L-arginine methyl ester) and blockade of soluble guanylyl cyclase (by ODQ; 1H-1,2,4-oxadiazolo[4,3-a]quinoxalin-1-one) produced similar inhibition as that produced by denudation. However, the resveratrol response was not affected by indomethacin (a cyclooxygenase inhibitor) and sulfaphenazole (an epoxygenase inhibitor). Intraluminal administration of an extracellular signal-regulated kinase (ERK) inhibitor (PD98059), but not an estrogen receptor blocker (ICI 182780), also reduced vasodilation by 50%. A nonselective K(+) channel blocker, tetraethylammonium (TEA), and a large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel inhibitor, iberiotoxin, produced identical inhibition of resveratrol-induced dilation. However, the dilation was insensitive to the inhibitors of ATP-sensitive K(+) channels and voltage-gated K(+) channels. Coadministration of L-NAME and iberiotoxin almost abolished the vasodilation induced by resveratrol.
CONCLUSIONS: Resveratrol elicits endothelium-dependent and -independent dilation of retinal arterioles. Endothelium-dependent dilation is mediated by the released NO, probably via NO synthase (NOS) activation by the ERK pathway and the subsequent activation of soluble guanylyl cyclase. The activation of BK(Ca) channels in smooth muscle contributes to the endothelium-independent dilation caused by resveratrol. A better understanding of the action of resveratrol on retinal vasculature may help shed light on its therapeutic potential for retinal vascular disease.
PMID: 17724212 [PubMed - indexed for MEDLINE]Free Article
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SIRT1 activation confers neuroprot... [Invest Ophthalmol Vis Sci. 2007] - PubMed - NCBI
Invest Ophthalmol Vis Sci. 2007 Aug;48
3602-9. SIRT1 activation confers neuroprotection in experimental optic neuritis.
Shindler KS, Ventura E, Rex TS, Elliott P, Rostami A.
F.M. Kirby Center for Molecular Ophthalmology, Department of Ophthalmology, University of Pennsylvania Scheie Eye Institute, Philadelphia, Pennsylvania 19104, USA. [email protected]
Abstract
PURPOSE: Axonal damage and loss of neurons correlate with permanent vision loss and neurologic disability in patients with optic neuritis and multiple sclerosis (MS). Current therapies involve immunomodulation, with limited effects on neuronal damage. The authors examined potential neuroprotective effects in optic neuritis by SRT647 and SRT501, two structurally and mechanistically distinct activators of SIRT1, an enzyme involved in cellular stress resistance and survival.
METHODS: Experimental autoimmune encephalomyelitis (EAE), an animal model of MS, was induced by immunization with proteolipid protein peptide in SJL/J mice. Optic neuritis developed in two thirds of eyes with significant retinal ganglion cell (RGC) loss detected 14 days after immunization. RGCs were labeled in a retrograde fashion with fluorogold by injection into superior colliculi. Optic neuritis was detected by inflammatory cell infiltration of the optic nerve.
RESULTS: Intravitreal injection of SIRT1 activators 0, 3, 7, and 11 days after immunization significantly attenuated RGC loss in a dose-dependent manner. This neuroprotective effect was blocked by sirtinol, a SIRT1 inhibitor. Treatment with either SIRT1 activator did not prevent EAE or optic nerve inflammation. A single dose of SRT501 on day 11 was sufficient to limit RGC loss and to preserve axon function.
CONCLUSIONS: SIRT1 activators provide an important potential therapy to prevent the neuronal damage that leads to permanent neurologic disability in optic neuritis and MS patients. Intravitreal administration of SIRT1 activators does not suppress inflammation in this model, suggesting that their neuroprotective effects will be additive or synergistic with current immunomodulatory therapies.
PMID: 17652729 [PubMed - indexed for MEDLINE]PMCID: PMC1964753Free PMC
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The effect of resveratrol in experimental catar... [Curr Eye Res. 2006] - PubMed - NCBI
Curr Eye Res. 2006 Feb;31(2):147-53.
The effect of resveratrol in experimental cataract model formed by sodium selenite.
Doganay S, Borazan M, Iraz M, Cigremis Y.
Department of Ophthalmology, Inonu University Medical Faculty, Turgut Ozal Medical Center, Malatya, Turkey. sdoganay2inonu.edu.tr
Abstract
PURPOSE: To investigate if resveratrol can prevent sodium selenite-induced experimental cataract model in rats.
METHODS: Forty-eight Spraque-Dawley rat pups were divided into 3 treatment groups: (1) normal saline-% 5 ethanol injected i.p. on postpatum day 10; (2) Na selenite (30 nmol/g body wt) injected s.c on day 10; (3) Na selenite s.c on day 10+resveratrol (40 mg/kg) i.p on days 10-13. On day 21, cataract development was graded by slit-lamp examination and photography. Encapsulated lenses and erythrocytes were analyzed for reduced glutathione (GSH) and malondialdehyde (MDA), a marker of lipid peroxidation. Lenses were also analyzed for total nitrite (TN).
RESULTS: All control lenses in group 1 were clear. In group 2, all rats developed cataracts (grade 3-grade 6), whereas in group 3, only 9 of 16 rats developed cataracts (grade 2-grade 3). The difference of cataract frequency between groups 2 and 3 was statistically significant (p<0.05). Group 3 lenses and erythrocytes had higher mean GSH and lower mean MDA levels than those in group 2 (p<0.05). TN was highest in group 3 and lowest in group 1 (p<0.05).
CONCLUSIONS: Resveratrol suppressed selenite-induced oxidative stress and cataract formation in rats. This protective effect was supported by higher GSH and lower MDA in lens and erythrocytes. The presence of oxidative stress in selenite cataract development and its prevention by resveratrol support the possibility that high natural consumption of resveratrol in food can help prevent human senile cataract.
PMID: 16500765 [PubMed - indexed for MEDLINE]
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Resveratrol reduces oxidation and prolife... [Chem Biol Interact. 2005] - PubMed - NCBI
Chem Biol Interact. 2005 Jan 15;151(2):143-9.
Resveratrol reduces oxidation and proliferation of human retinal pigment epithelial cells via extracellular signal-regulated kinase inhibition.
King RE, Kent KD, Bomser JA.
Department of Food Science and Technology, Ohio State University, 1787 Neil Ave., Columbus, OH 43210, USA.
Abstract
Epidemiological evidence suggests that moderate wine consumption and antioxidant-rich diets may protect against age-related macular degeneration (AMD), the leading cause of vision loss among the elderly. Development of AMD and other retinal diseases, such as proliferative vitreoretinopathy (PVR), is associated with oxidative stress in the retinal pigment epithelium (RPE), a cell layer responsible for maintaining the health of the retina by providing structural and nutritional support. We hypothesize that resveratrol, a red wine polyphenol, may be responsible, in part, for the health benefits of moderate red wine consumption on retinal disease. To test this hypothesis, the antioxidant and antiproliferative effects of resveratrol were examined in a human RPE cell line (designated ARPE-19). Cell proliferation was determined using the bromodeoxyuridine (BrdU) assay, intracellular oxidation was assessed by dichlorofluorescein fluorescence, and activation of the mitogen-activated protein kinase (MAPK) cascade was measured by immunoblotting. Treatment with 50 and 100 micromol/L resveratrol significantly reduced proliferation of RPE cells by 10% and 25%, respectively (P<0.05). This reduction in proliferation was not associated with resveratrol-induced cytotoxicity. Resveratrol (100 micromol/L) inhibited basal and H2O2-induced intracellular oxidation and protected RPE cells from H2O2-induced cell death. The observed reduction in cell proliferation was associated with inhibition of mitogen activated protein kinase/ERK (MEK) and extracellular signal-regulated kinase (ERK 1/2) activities at concentrations of resveratrol as low as 5 micromol/L. These results suggest that resveratrol can reduce oxidative stress and hyperproliferation of the RPE.
PMID: 15698585 [PubMed - indexed for MEDLINE]
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Resveratrol inhibits neuronal apoptosis and elevate... [Diabetes. 2010] - PubMed - NCBI
Resveratrol inhibits neuronal apoptosis and elevated Ca2+/calmodulin-dependent protein kinase II activity in diabetic mouse retina.
Kim YH, Kim YS, Kang SS, Cho GJ, Choi WS.
Department of Anatomy and Neurobiology, Gyeongsang National University, Jinju, Gyeongnam, Korea.
Abstract
OBJECTIVE: This study investigated the effects of resveratrol, a natural polyphenol with neuroprotective properties, on retinal neuronal cell death mediated by diabetes-induced activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII).
RESEARCH DESIGN AND METHODS: Diabetes was induced in C57BL/6 mice by five consecutive intraperitoneal injections of 55 mg/kg streptozotocin (STZ). Control mice received buffer. All mice were killed 2 months after the injections, and the extent of neuronal cell death, CaMKII, and phospho-CaMKII protein expression levels and CaMKII kinase activity were examined in the retinas. To assess the role of CaMKII in the death of retinal neurons, a small-interfering RNA (siRNA) or specific inhibitor of CaMKII was injected into the right vitreous humor, and vehicle only was injected into the left vitreous humor, 2 days before death. Resveratrol (20 mg/kg) was administered by oral gavage daily for 4 weeks, beginning 1 month after the fifth injection of either STZ or buffer.
RESULTS: The death of retinal ganglion cells (RGCs), CaMKII, phospho-CaMKII protein levels, and CaMKII activity were all greatly increased in the retinas of diabetic mice compared with controls, 2 months after induction of diabetes. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL)-positive signals co-localized with CaMKII- and phospho-CaMKII immunoreactive RGCs. However, in addition to CaMKII knockdown and inhibition by siRNA or a specific inhibitor, respectively, resveratrol provided complete protection from diabetes-induced retinal cell death.
CONCLUSIONS: In the present study, resveratrol prevented diabetes-induced RGC death via CaMKII downregulation, implying that resveratrol may have potential therapeutic applications for prevention of diabetes-induced visual dysfunction
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Retinal protective effects of resveratro... [Korean J Ophthalmol. 2010] - PubMed - NCBI
Korean J Ophthalmol. 2010 Apr;24(2):108-18. Epub 2010 Apr 6.
Retinal protective effects of resveratrol via modulation of nitric oxide synthase on oxygen-induced retinopathy.
Kim WT, Suh ES.
Department of Pediatrics, Catholic University of Daegu School of Medicine, Daegu, Korea.
Abstract
PURPOSE: Retinopathy of prematurity (ROP) is one of the leading causes of blindness, with retinal detachment occurring due to oxygen toxicity in preterm infants. Recently, advances in neonatal care have led to improved survival rates for preterm infants, and ROP has increased in incidence. In the present study, we aimed to determine whether or not resveratrol exhibits protective effects in an animal model of ROP and in primary retinal cell cultures of neonatal rat via nitric oxide (NO)-modulating actions using western blotting and real-time PCR with inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS) and neuronal NOS (nNOS) antibodies and mRNAs.
METHODS: In an in vivo oxygen-induced retinopathy (OIR) model, cyclic hyperoxia was induced with 80% O(2) for one day and 21% O(2) for one day from P1 to P14 in newborn Sprague-Dawley (SD) rats. Resveratrol was injected intravitreally for seven days and rats were sacrificed at P21. In vitro OIR primary retinal cell culture was performed using P0-2 SD rats. Hyperoxia injuries were induced through 100% O(2) exposure for six hours. Western blotting and real-time PCR using iNOS, eNOS, nNOS antibodies and primers were performed in the rat model of ROP and the dispersed retinal cell culture.
RESULTS: In both in vivo and in vitro OIR, the expression of iNOS antibody and mRNA was increased and of eNOS and nNOS were reduced in the resveratrol-treated group.
CONCLUSIONS: In conclusion, resveratrol appeared to exert retinal protective effects via modulation of NO-mediated mechanism in in vivo and in vitro OIR models.
PMID: 20379461 [PubMed - indexed for MEDLINE]PMCID: PMC2850998Free PMC Article
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Inhibition of apoptosis in human r... [Invest Ophthalmol Vis Sci. 2010] - PubMed - NCBI
Inhibition of apoptosis in human retinal pigment epithelial cells treated with benzo(e)pyrene, a toxic component of cigarette smoke.
Mansoor S, Gupta N, Patil AJ, Estrago-Franco MF, Ramirez C, Migon R, Sapkal A, Kuppermann BD, Kenney MC.
Department of Ophthalmology, School of Medicine, University of California, Irvine, CA 92868, USA.
Abstract
PURPOSE: To study the inhibitory effects of some agents or drugs (inhibitors) on benzo(e)pyrene (B(e)P)-induced cell death and apoptosis on human retinal pigment epithelial (ARPE-19) cells in vitro.
METHODS: ARPE-19 cells were pretreated with varying concentrations of different classes of inhibitors (calpain, benzyl isothiocyanate [BITC], simvastatin, epicatechin, genistein, resveratrol, and memantine) before B(e)P exposure. Cell viability (CV) was determined by a trypan blue dye-exclusion assay. Caspase-3/7 and caspase-9 activities were measured by fluorochrome assays. The production of reactive oxygen/nitrogen species (ROS/RNS) was measured with 2',7'-dicholorodihydrofluorescein diacetate dye assay.
RESULTS: At 30-microM concentrations, the genistein, resveratrol, and memantine inhibitors were able to reverse significantly the loss of cell viability, the activation of caspase-3/7 and caspase-9, and the production of ROS/RNS in ARPE-19 cell cultures. Memantine was the most potent and genistein was the least effective inhibitor in blocking the B(e)P-induced effects. Calpain, BITC, simvastatin, and epicatechin did not reverse the loss of cell viability in B(e)P-treated ARPE-19 cells. As a matter of fact, at the concentrations studied (15, 30, 45 microM), the BITC plus B(e)P-treated cultures showed significantly lower cell viability than the B(e)P-treated culture alone, suggesting BITC-related toxicity.
CONCLUSIONS: Genistein, resveratrol, and memantine can reverse the apoptosis and oxidant production generated by B(e)P, a toxic element of smoking. These inhibitors may be beneficial against retinal diseases associated with the loss of RPE cells.
PMID: 19959636 [PubMed - indexed for MEDLINE]
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"""In addition, these results have uncovered a sirtuin-independent pathway by which resveratrol regulates angiogenesis."""
Resveratrol regulates pathologic angiogenesis by... [Am J Pathol. 2010] - PubMed - NCBI
Am J Pathol. 2010 Jul;177(1):481-92. Epub 2010 May 14.
Resveratrol regulates pathologic angiogenesis by a eukaryotic elongation factor-2 kinase-regulated pathway.
Khan AA, Dace DS, Ryazanov AG, Kelly J, Apte RS.
Departments of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, USA.
Abstract
Abnormal angiogenesis is central to the pathophysiology of diverse disease processes including cancers, ischemic and atherosclerotic heart disease, and visually debilitating eye disease. Resveratrol is a naturally occurring phytoalexin that has been demonstrated to ameliorate and decelerate the aging process as well as blunt end organ damage from obesity. These effects of resveratrol are largely mediated by members of the sirtuin family of proteins. We demonstrate that resveratrol can inhibit pathological angiogenesis in vivo and in vitro by a sirtuin-independent pathway. Resveratrol inhibits the proliferation and migration of vascular endothelial cells by activating eukaryotic elongation factor-2 kinase. The active kinase in turn phosphorylates and inactivates elongation factor-2, a key mediator of ribosomal transfer and protein translation. Functional inhibition of the kinase by gene deletion in vivo or RNA as well as pharmacological inhibition in vitro is able to completely reverse the effects of resveratrol on blood vessel growth. These studies have identified a novel and critical pathway that promotes aberrant vascular proliferation and one that is amenable to modulation by pharmacological means. In addition, these results have uncovered a sirtuin-independent pathway by which resveratrol regulates angiogenesis.
resveratrol tetramer: Vaticanol C, a resveratrol tetramer, activ... [Nutr Metab (Lond). 2010] - PubMed - NCBI
lymph node and lung methastasis Vaticanol C, a novel resveratrol ... [Cancer Chemother Pharmacol. 2007] - PubMed - NCBI
Quote:
Vaticanol C, a resveratrol tetramer, activates PPARalpha and PPARbeta/delta in vitro and in vivo.
Tsukamoto T, Nakata R, Tamura E, Kosuge Y, Kariya A, Katsukawa M, Mishima S, Ito T, Iinuma M, Akao Y, Nozawa Y, Arai Y, Namura S, Inoue H.
Department of Food Science and Nutrition, Nara Women's University, Nara, 630-8506, Japan. [email protected].
Abstract
ABSTRACT:
BACKGROUND: Appropriate long-term drinking of red wine is associated with a reduced risk of cardiovascular disease. Resveratrol, a well-known SIRT1 activator is considered to be one of the beneficial components contained in red wine, and also developed as a drug candidate. We previously demonstrated that resveratrol protects brain against ischemic stroke in mice through a PPARalpha-dependent mechanism. Here we report the different effects of the oligomers of resveratrol.
METHODS: We evaluated the activation of PPARs by epsilon-viniferin, a resveratrol dimer, and vaticanol C, a resveratrol tetramer, in cell-based reporter assays using bovine arterial endothelial cells, as well as the activation of SIRT1. Moreover, we tested the metabolic action by administering vaticanol C with the high fat diet to wild-type and PPARalpha-knockout male mice for eight weeks.
RESULTS: We show that vaticanol C activates PPARalpha and PPARbeta/delta in cell-based reporter assays, but does not activate SIRT1. epsilon-Viniferin shows a similar radical scavenging activity as resveratrol, but neither effects on PPARs and SIRT-1. Eight-week intake of vaticanol C with a high fat diet upregulates hepatic expression of PPARalpha-responsive genes such as cyp4a10, cyp4a14 and FABP1, and skeletal muscle expression of PPARbeta/delta-responsive genes, such as UCP3 and PDK4 (pyruvate dehydrogenase kinase, isoform 4), in wild-type, but not PPARalpha-knockout mice.
CONCLUSION: Vaticanol C, a resveratrol tetramer, activated PPARalpha and PPARbeta/delta in vitro and in vivo. These findings indicate that activation of PPARalpha and PPARbeta/delta by vaticanol C may be a novel mechanism, affording beneficial effects against lifestyle-related diseases.
PMID: 20504373 [PubMed - in process]PMCID: PMC2882917Free PMC Article
Quote:
Vaticanol C, a novel resveratrol tetramer, reduces lymph node and lung metastases of mouse mammary carcinoma carrying p53 mutation.
Shibata MA, Akao Y, Shibata E, Nozawa Y, Ito T, Mishima S, Morimoto J, Otsuki Y.
Department of Anatomy and Cell Biology, Division of Basic Medicine I, Osaka Medical College, 2-7, Daigaku-machi, Takatsuki, Japan. [email protected]
Abstract
PURPOSE: The effects of vaticanol C (Vat-C), a novel resveratrol tetramer, were studied in a mouse metastatic mammary cancer model carrying mutations in p53 that produce a metastatic spectrum similar to that seen in human breast cancers.
METHODS: Mammary tumors, induced by inoculation of syngeneic BALB/c mice with BJMC3879 cells, were subsequently treated with Vat-C at 0, 100 and 200 ppm in their diet.
RESULTS: The in vitro study demonstrated that Vat-C induced apoptosis, as inferred by morphological changes, nucleosomal DNA fragmentation and elevated activities of caspases. Although tumor volumes were not apparently suppressed in mice treated with Vat-C, the multiplicity of lymph node metastasis was significantly decreased in the 200-ppm group. Furthermore, the multiplicity of lung metastasis was also significantly lower in the 200-ppm group. In any category of organ metastasis, the number of organs with metastasis tended to be lower in the 200-ppm group, but these findings were not statistically significant. The levels of apoptosis were significantly higher in the 200-ppm group, but DNA synthesis only a tended to be lower in this group. Microvessel density in tumors also tended to be lower in the Vat-C-treated groups. Moreover, the numbers of lymphatic vessels having intraluminal tumor cells was significantly lower in mammary tumors of mice given 100 and 200-ppm Vat-C, indicating a reduction in migrating tumor cells into the lymphatic vessels of tumor tissue.
CONCLUSIONS: These results suggest that the observed antimetastatic activity of Vat-C may be of clinical significance as an adjuvant therapy in metastatic human breast cancer having p53 mutations, and may also be useful as a chemopreventative of breast cancer development.
PMID: 17256131 [PubMed - indexed for MEDLINE]
activation of the apoptotic arm of the UPR and its downstream effector CHOP/GADD153 is involved, at least in part, in RES-induced apoptosis in Burkitt's lymphoma cells Updates of mTOR inhibitors. [Anticancer Agents Med Chem. 2010] - PubMed - NCBI
Resveratrol-induced p53-independent apoptosis of human nasopharyngeal carcinoma cells is correlated with the downregulation of DeltaNp63. Resveratrol-induced p53-independent apoptos... [Cancer Gene Ther. 2010] - PubMed - NCBI
so its good for asthma to? Resveratrol impairs the release of ster... [J Pharmacol Exp Ther. 2010] - PubMed - NCBI
Resveratrol protects human lens epithelial cells against H2O2-induced oxidative stress by increasing catalase, SOD-1, and HO-1 expression - Resveratrol protects human lens epithelial cells aga... [Mol Vis. 2010] - PubMed - NCBI
**broken link removed**
neuroprotective effect of resv via anti-apoptosis **broken link removed**
Anticancer Agents Med Chem. 2010 Aug 10. [Epub ahead of print]
Updates of mTOR inhibitors.
Zhou H, Luo Y, Huang S.
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA.
Abstract
Mammalian target of rapamycin (mTOR) is a central controller of cell growth, proliferation, metabolism and angiogenesis. mTOR signaling is often dysregulated in various human diseases and thus attracts great interest in developing drugs that target mTOR. Currently it is known that mTOR functions as two complexes, mTOR complex 1/2 (mTORC1/2). Rapamycin and its analogs (all termed rapalogs) first form a complex with the intracellular receptor FK506 binding protein 12 (FKBP12) and then bind a domain separated from the catalytic site of mTOR, blocking mTOR function. Rapalogs are selective for mTORC1 and effective as anticancer agents in various preclinical models. In clinical trials, rapalogs have demonstrated efficacy against certain types of cancer. Recently, a new generation of mTOR inhibitors, which compete with ATP in the catalytic site of mTOR and inhibit both mTORC1 and mTORC2 with a high degree of selectivity, have been developed. Besides, some natural products, such as epigallocatechin gallate (EGCG), caffeine, curcumin and resveratrol, have been found to inhibit mTOR as well. Here, we summarize the current findings regarding mTOR signaling pathway and review the updated data about mTOR inhibitors as anticancer agents.
That's basically what I said as the 'rapalogs' are selective for a specific mTor and cell. Hell, tea is an anti-cancer, too, and we know nothing we are taking is competing with ATP for if it was we'd feel like crap and cancer patients would be dying from mTor inhibition!
Also, clowns, with how well curcumin, tea, ECGC, and resveratrol work, there may actually be a BENEFIT to what mTor they may be inhibiting as the other mTor is obviously taking over. Seeing that tea, caffeine, and resveratrol also cause loss of FAT, that would be an obvious mTor inhibition benefit which may only affect fat cells just like IGF causes muscles to uptake glucose while causing fat cells to not.
Quote:
Rapalogs are selective for mTORC1 and effective as anticancer agents in various preclinical models. In clinical trials, rapalogs have demonstrated efficacy against certain types of cancer. Recently, a new generation of mTOR inhibitors, which compete with ATP in the catalytic site of mTOR and inhibit both mTORC1 and mTORC2 with a high degree of selectivity, have been developed
Quote:
Consistent with its role in cell proliferation, the mTOR pathway is frequently hyperactivated in a number of human malignancies and is thus considered to be an attractive target for anti-cancer therapy. Rapamycin and its analogs (rapalogs) function as allosteric inhibitors of mTORC1 and are currently used in the treatment of advanced renal cell carcinoma. Rapamycin and its derivatives bind to the small immunophilin FKBP12 to inhibit mTORC1 signalling through a poorly understood mechanism. Rapamycin/FKBP12 efficiently inhibit some, but not all, functions of mTOR and hence much interest has been placed in the development of drugs that target the kinase activity of mTOR directly. Several novel active-site inhibitors of mTOR, which inhibit both mTORC1 and mTORC2, were developed in the last year.
