Resveratrol potently reduces prostaglandin E2 production and free radical formation in lipopolysaccharide-activated primary rat microglia (original) (raw)
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Resveratrol inhibits prostaglandin formation in IL-1β-stimulated SK-N-SH neuronal cells
Journal of Neuroinflammation, 2009
Resveratrol, a polyphenol present in grapes and red wine, has been studied due to its vast pharmacological activity. It has been demonstrated that resveratrol inhibits production of inflammatory mediators in different in vitro and in vivo models. Our group recently demonstrated that resveratrol reduced the production of prostaglandin (PG) E2 and 8-isoprostane in rat activated microglia. In a microglial-neuronal coculture, resveratrol reduced neuronal death induced by activated microglia. However, less is known about its direct roles in neurons. In the present study, we investigated the effects of resveratrol on interleukin (IL)-1β stimulated SK-N-SH cells. Resveratrol (0.1-5 μM) did not reduce the expression of cyclooxygenase (COX)-2 and microsomal PGE2 synthase-1 (mPGES-1), although it drastically reduced PGE2 and PGD2 content in IL-1β-stimulated SK-N-SH cells. This effect was due, in part, to a reduction in COX enzymatic activity, mainly COX-2, at lower doses of resveratrol. The p...
Biochemical Pharmacology, 2000
Resveratrol is a natural molecule with antioxidant action. Moreover, resveratrol is also considered to be a molecule with anti-inflammatory action, an effect attributed to suppression of prostaglandin (PG) biosynthesis. The aim of the present study was to investigate the effects of resveratrol, a polyphenol present in most red wines, on reactive oxygen species formation as well as on arachidonic acid (AA) release, cyclooxygenase expression, and PG synthesis in murine resident peritoneal macrophages. Results show that resveratrol exerted a strong inhibitory effect on superoxide radical (O 2 Ϫ ) and hydrogen peroxide (H 2 O 2 ) produced by macrophages stimulated by lipopolysaccharides (LPS) or phorbol esters (PMA). Resveratrol also significantly decreased [ 3 H]AA release induced by LPS and PMA or by exposure to O 2
Protective effect of resveratrol against lipopolysaccharide-induced oxidative stress in rat brain
Brain Injury, 2009
Primary objective: To study the protective effect of resveratrol on endotoxemia-induced neurotoxicity. Methods: Rats were pre-treated during 7 days with 20 mg kg À1 body weight (b.w.) resveratrol and challenged with a single dose of lipopolysaccharide (LPS: 8 mg kg À1 b.w.) for 24 hours. Brains were harvested to determine LPS-induced lipoperoxidation level, antioxidant enzyme activities, nitric monoxide (NO) and iron distribution as well as the impact of resveratrol on these parameters. Results: Resveratrol counteracted LPS-induced brain malondialdehyde (MDA) level and antioxidant enzyme activities depletion as superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD). Resveratrol also reversed LPS-induced brain and plasma NO elevation as well as iron sequestration from plasma to brain compartment. Conclusion: The data suggest that resveratrol is capable of alleviating LPS-induced neurotoxicity by a mechanism that may involve iron shuttling proteins.
Oxidative Medicine and Cellular Longevity, 2015
Resveratrol is a phenolic phytochemical, with a stilbene backbone, derived from edible plants such as grape and peanut. It is a bioactive molecule with physiological effects on multiple organ systems. Its effects range from the neuroprotective to the nephroprotective, including cardiovascular, neuronal, and antineoplastic responses as a part of its broad spectrum of action. In this review, we examine the effects of resveratrol on the following organ systems: the central nervous system, including neurological pathology such as Parkinson’s and Alzheimer’s disease; the cardiovascular system, including disorders such as atherosclerosis, ischemia-reperfusion injury, and cardiomyocyte hypertrophy; the kidneys, including primary and secondary nephropathies and nephrolithiasis; multiple forms of cancer; and metabolic syndromes including diabetes. We emphasize commonalities in extracellular matrix protein alterations and intracellular signal transduction system induction following resveratro...
Resveratrol differentially modulates inflammatory responses of microglia and astrocytes
Journal of Neuroinflammation, 2010
Background Inflammatory responses in the CNS mediated by activated glial cells play an important role in host-defense but are also involved in the development of neurodegenerative diseases. Resveratrol is a natural polyphenolic compound that has cardioprotective, anticancer and anti-inflammatory properties. We investigated the capacity of resveratrol to protect microglia and astrocyte from inflammatory insults and explored mechanisms underlying different inhibitory effects of resveratrol on microglia and astrocytes. Methods A murine microglia cell line (N9), primary microglia, or astrocytes were stimulated by LPS with or without different concentrations of resveratrol. The expression and release of proinflammatory cytokines (TNF-α, IL-1β, IL-6, MCP-1) and iNOS/NO by the cells were measured by PCR/real-time PCR and ELISA, respectively. The phosphorylation of the MAP kinase superfamily was analyzed by western blotting, and activation of NF-κB and AP-1 was measured by luciferase report...
International Immunopharmacology, 2017
The health benefits of bio-active phenolic compounds have been largely investigated in vitro at concentrations which exceed those reachable in vivo. We investigated and compared the anti-inflammatory effects of resveratrol, hydroxytyrosol and oleuropein at physiologically relevant concentrations by using in vitro models of inflammation. Human granulocytes and monocytes were stimulated with phorbol myristate acetate (PMA) and the ability of resveratrol, hydroxytyrosol and oleuropein to inhibit the oxidative burst and CD11b expression was measured. Nitric oxide (NO), prostaglandin E2 (PGE2) levels, COX-2, iNOS, TNFα, IL-1β and miR-146a expression and activation of the transcription factor Nrf2 were evaluated in macrophages RAW 264.7 stimulated with LPS (1 μg/ml) for 18 h, exposed to resveratrol, hydroxytyrosol and oleuropein (5 and 10 μM). Synergistic effects were explored as well, together with the levels of PGE2, COX-2 and IL-1β expression in macrophages after 6 h of LPS stimulation. PGE2 and COX-2 expression were also assessed on human monocytes. All the tested compounds inhibited granulocytes oxidative burst in a concentration dependent manner and CD11b expression was also significantly counteracted by resveratrol and hydroxytyrosol. The measurement of oxidative burst in human monocytes produced similar effects being resveratrol more active. Hydroxytyrosol and resveratrol inhibited the production of NO and PGE2 but did not reduce iNOS, TNFα or IL-1β gene expression in LPS-stimulated RAW 264.7 for 18 h. Resveratrol slightly decreased COX-2 expression after 18 h but not after 6 h, but reduced PGE2 levels after 6 h. Resveratrol and hydroxytyrosol 10 μM induced NRf2 nuclear translocation and reduced miR-146a expression in LPS treated RAW 264.7. Overall, we reported an anti-inflammatory effect of resveratrol and hydroxytyrosol at low, nutritionally relevant concentrations, involving the inhibition of granulocytes and monocytes activation, the modulation of miR-146a expression and the activation of Nrf2. A regular dietary intake of resveratrol and hydroxytyrosol may be a useful complementary strategy to control inflammatory diseases.
Lack of effect of oral administration of resveratrol in LPS-induced systemic inflammation
European Journal of Nutrition, 2011
Purpose The high mortality index due to sepsis and the lack of an effective treatment requires the search for new compounds that can serve as therapy for this disease. Resveratrol, a well-known anti-inflammatory natural compound, might be a good candidate for the treatment of sepsis. The aim of this work was to study the effects of oral administration of resveratrol, before and after sepsis initiation, on inflammation markers in a murine model of endotoxin-induced sepsis. Methods Sprague-Dawley male rats were treated with resveratrol the 3 days prior to LPS administration and 45 min later. Hematological parameters, TNF-a, IL-1b and CINC-1, FRAP and TBARS levels were determined. Resveratrol and resveratrol-derived metabolites profile in plasma was compared after oral and intraperitoneal administration. Results Oral treatment with resveratrol had no apparent systemic protective effects. However, resveratrol reduced the levels of lipid peroxidation in the small intestine and colon. Importantly, the administration of LPS caused a decrease in resveratrol absorption. When resveratrol bioavailability after i.p. administration was compared to that observed after oral administration, a different profile of resveratrol metabolites was found in plasma. Conclusion These results highlight the importance of studying the bioavailability of the assayed compounds in the experimental models used to be able to choose the best route of administration depending on the target organ and to determine which compounds or derived metabolites are effective treating the studied disease.
Protective Effect of Resveratrol against Hypoxia-Induced Neural Oxidative Stress
Journal of Personalized Medicine
Oxidative stress plays an important role in brain aging and in neurodegenerative diseases. New therapeutic agents are necessary to cross the blood–brain barrier and target disease pathogenesis without causing disagreeable side effects. Resveratrol (RSV) may act as a neuroprotective compound, but little is known about its potential in improving the cognitive and metabolic aspects that are associated with neurodegenerative diseases. The objective of this study was to investigate the protective effects and the underlying mechanisms of RSV against hypoxia-induced oxidative stress in neuronal PC12 cells. For the induction of the hypoxia model, the cells were exposed to oxygen-deprived gas in a hypoxic chamber. Cell cycle and apoptosis were analyzed by a fluorescence activated cell sorting (FACS) analysis. The intracellular reactive oxygen species (ROS) level was analyzed by using dichlorodihydrofluorescein diacetate (DCFDA) and 5-(and-6)-chloromethyl-2’,7’-dichlorodihydrofluorescein diac...