stilbenes and Edema

In this study, we present a novel product consisted of red grape cells (RGC) grown in culture and evaluated its effect on human LDL oxidation (in vitro) and inflammatory stress (in an in vivo rat model). We analyzed RGC for its polyphenols content and characterized RGC-derived resveratrol (RES) and its properties; and finally, we characterized the pharmacokinetic profile of RGC-RES in human plasma. RGC has demonstrated a strong inhibitory effect on LDL oxidation with IC50 as low as 8.0 μg/ml. RGC significantly reduced rats inflamed paw size induced by carrageenan injection. LC/MS analysis has shown that the main polyphenol in RGC was RES with one hexose moiety. The human pharmacokinetic analysis (clinicaltrials.gov NCT01747252) revealed relatively high bioavailability and two distinctly separated plasma concentration peaks at 1 and 5 h. The present study demonstrates antioxidant and anti-inflammatory traits of RGC that warrants further research in both pre-clinical and clinical settings.

Topics: Adult; Animals; Biological Availability; Carrageenan; Cross-Over Studies; Edema; Humans; Indomethacin; Inflammation; Lipoproteins, LDL; Male; Oxidation-Reduction; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Vitis

Topics: Animals; Anti-Inflammatory Agents; Chondrocytes; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dinoprostone; Edema; Gene Expression Regulation; Glucosides; Hindlimb; Iodoacetic Acid; Lipopolysaccharides; Male; Matrix Metalloproteinase 13; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Osteoarthritis; Polygonum; Primary Cell Culture; Rats; RAW 264.7 Cells; Stilbenes

Resveratrol and curcumin, as natural flavones products, have good therapeutic effect in acute and chronic inflammation; on the other hand, tetramethylpyrazine (TMP) has angiogenesis and vessel protection effect as well as anti-inflammatory function. In this paper, the anti-inflammatory effect of the tetramethylpyrazine, resveratrol and curcumin (TRC) combination in acute and chronic inflammation was reported in vivo.. The dose of the combined three natural products was optimized based on the acute paw swelling mouse model with a Uniform Design methodology. The therapeutic effect of TRC combination on chronic inflammation was investigated by using the collagen-induced arthritis (CIA) rat model based upon the following indexes: the volume of paw swelling, arthritis score, serum mediators and histological examination as well as immunohistochemical staining. The levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were measured and the pathological sections of liver and kidney were analysed. LD. The results showed this formulation could provide a novel potent treatment for acute and chronic inflammation (RA) without side effect like gastric injury occurring in NSAIDs.

Topics: Alanine Transaminase; Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Aspartate Aminotransferases; Cartilage; Curcumin; Cytokines; Drug Combinations; Edema; Female; Inflammation; Joints; Kidney; Liver; Male; Mice; NF-kappa B; Phytotherapy; Plant Extracts; Pyrazines; Rats, Sprague-Dawley; Resveratrol; Stilbenes

Resveratrol-phospholipid complex (Phytosome®) (RSVP) was found better aqueous soluble and permeable than free resveratrol (RSV). RSVPs were incorporated in polymeric patch prepared by solvent casting method using Eudragit RL 100, PVP K30, and PEG 400 for application on dermal sites for sustained treating of inflammation. Prepared patches were evaluated for various physicochemical properties, surface morphology by SEM, TEM, and compatibility of patch components by FT-IR and DSC studies. Optimized formulation (F9) gave 95.79 ± 3.02% drug release and 51.36% (4.28 ± 0.48 mg/cm

Topics: Acrylic Resins; Administration, Cutaneous; Animals; Anti-Inflammatory Agents; Carrageenan; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Delivery Systems; Edema; Inflammation; Male; Permeability; Phospholipids; Polyethylene Glycols; Polymers; Rabbits; Rats; Rats, Wistar; Resveratrol; Skin; Skin Absorption; Stilbenes; Transdermal Patch

Resveratrol and gallic acid, a lipophilic and a hydrophilic phenol, were co-loaded in innovative, biocompatible nanovesicles conceived for ensuring the protection of the skin from oxidative- and inflammatory-related affections. The basic vesicles, liposomes and glycerosomes, were produced by a simple, one-step method involving the dispersion of phospholipid and phenols in water or water/glycerol blend, respectively. Liposomes and glycerosomes were modified by the addition of poloxamer, a stabilizer and viscosity enhancer, thus obtaining viscous or semisolid dispersions of structured vesicles. The vesicles were spherical, unilamellar and small in size (~70 nm in diameter). The superior ability of the poloxamer-structured vesicles to promote the accumulation of both phenols in the skin was demonstrated, as well as their low toxicity and great ability to protect fibroblasts from chemically-induced oxidative damage. The in vivo administration of the vesicular phenols on TPA (phorbol ester)-exposed skin led to a significant reduction of oedema and leukocyte infiltration.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Cell Survival; Edema; Female; Fibroblasts; Gallic Acid; Liposomes; Mice; Oxidative Stress; Poloxamer; Resveratrol; Skin; Skin Absorption; Stilbenes; Swine

The present work endeavors for development and evaluation of resveratrol loaded niosomal hydrogel system for its anti-inflammatory action. Niosomes were prepared by thin film hydration and ether injection methods employing Span 80 as a surfactant at three different levels. Best optimized formulation was selected on the basis of entrapment efficiency (% EE), mean particle size, sedimentation volume, and microscopy. The vesicular and spherical nature of the niosomes was confirmed by optical microscopy and transmission electron microscope (TEM). Further, resveratrol entrapped niosomal gel was prepared by gelling in Carbopol 934, and evaluated for pH, viscosity, and in vitro release, employing dialysis membrane method. The in vitro release data after fitting to various models revealed it to follow Korsmeyer-Pappas model. Ex vivo permeation studies witnessed high permeation and deposition of resveratrol in skin when compared to plain resveratrol. Dermatokinetic studies elaborated that niosomal gel enhanced the biological half-life and reduced T

Topics: Administration, Topical; Animals; Dialysis; Edema; Hydrogel, Polyethylene Glycol Dimethacrylate; Kinetics; Liposomes; Male; Pain; Particle Size; Rats, Wistar; Resveratrol; Rheology; Skin Absorption; Stilbenes; Surface-Active Agents; Suspensions

Resveratrol is a natural compound with a plethora of activities as well as limitations. We recently reported a series of resveratrol-salicylate analogs with potential chemopreventive activity. Herein, we report the anti-inflammatory and antioxidant properties of these resveratrol derivatives. Using an in vitro COX inhibition assay, and two in vivo protocols (carrageenan-induced peritonitis and paw edema), we identified a novel compound (C10) as a potent anti-inflammatory agent. The enhanced potency of C10 was associated with the ability of C10 to decrease the activity of myeloperoxidase (MPO) enzyme at 10mg/kg, whereas resveratrol and it's natural analog (TMS) did not exert the same effect. Additionally, C10 significantly reduced the concentration of intracellular reactive oxygen species. Because of the proven association between cancer, inflammation, and oxidative stress, we believe that C10 is a promising chemopreventive molecule.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Carrageenan; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Edema; Hep G2 Cells; Humans; Hydrogen Peroxide; Mice; Molecular Structure; Oxidative Stress; Peritonitis; Prostaglandin-Endoperoxide Synthases; Reactive Oxygen Species; Resveratrol; Salicylates; Stilbenes; Structure-Activity Relationship

Palmitoylethanolamide (PEA), a special food for medical purposes, has anti-inflammatory and neuroprotective effects. Nevertheless, PEA lacks direct ability to prevent free radical formation. Polydatin (PLD), a natural precursor of resveratrol, has antioxidant activity. The combination of PEA and PLD could have beneficial effects on oxidative stress induced by inflammatory processes. In the present study, we compared the effects of micronized PEA (PEA-m) and PLD association (PEA-m+PLD) with a new co-micronized composite containing PEA and PLD (m(PEA/PLD)) in the rat paw model of carrageenan (CAR)-induced acute inflammation. Intraplantar injection of CAR led to a time-dependent development of peripheral inflammation, in terms of paw edema, cytokine release in paw exudates, nitrotyrosine formation, inducible nitric oxide synthase and cyclooxygenase-2 expression. m(PEA/PLD) reduced all measured parameters. Thermal hyperalgesia and mechanical allodynia were also markedly reduced. At the spinal cord level, manganese superoxide dismutase (MnSOD) was found to be nitrated and subsequently deactivated. Further, m(PEA/PLD) treatment increased spinal MnSOD expression, prevented IkB-α degradation and nuclear factor-κB translocation, suggesting a possible role on central sensitization. m(PEA/PLD) showed more robust anti-inflammatory and anti-hyperalgesic effects compared to the simple association of PEA-m and PLD. This composite formulation approach opens a new therapeutic strategy for the development of novel non-narcotic anti-hyperalgesic agents.

Topics: Active Transport, Cell Nucleus; Administration, Oral; Amides; Animals; Carrageenan; Cell Line, Tumor; Cell Nucleus; Cyclooxygenase 2; Cytokines; Disease Models, Animal; Drug Compounding; Drug Interactions; Edema; Ethanolamines; Gene Expression Regulation, Enzymologic; Glucosides; Hyperalgesia; Inflammation; Male; Neutrophil Infiltration; NF-KappaB Inhibitor alpha; Nitric Oxide Synthase Type II; Palmitic Acids; Proteolysis; Rats; Rats, Sprague-Dawley; Stilbenes; Superoxide Dismutase; Transcription Factor RelA; Tyrosine

Evidence shows beneficial effects of resveratrol (RES) on human health. However, its poor aqueous solubility limits therapeutic effectiveness. Thus, the use of nanostructured delivery systems for RES, such as a liquid-crystalline system (LCS), could be viable. The purpose of this study was to develop, characterize, and determine the in vivo effectiveness of a RES-loaded LCS. We studied an LCS containing silicon glycol copolymer, polyether functional siloxane, and the polymeric dispersion carbomer homopolymer type B (C974) in the ratio 20:55:25 with and without RES. Results obtained using polarized light microscopy, small-angle X-ray scattering, and rheology analysis showed that the RES-loaded LCS system presents a lamellar structure and behaves as a non-Newtonian fluid presenting pseudoplastic (the apparent viscosity decreases as the stress increases) and thixotropic (the apparent viscosity decreases with the duration of stress) behaviors. Cytotoxicity studies showed that the formulation components are noncytotoxic. Topical application of a RES-loaded LCS protected hairless mice from UVB-irradiation-induced skin damage by inhibiting edema, neutrophil recruitment, lipid hydroperoxide and superoxide anion production, gp91phox mRNA expression, and oxidative stress. The RES-loaded LCS maintained 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric reducing abilities, catalase activity, reduced glutathione levels, and mRNA expression of glutathione peroxidase 1 and glutathione reductase. The RES-loaded LCS also up-regulated matrix metalloproteinase-9 activity, IL-10 production, and mRNA expression of transcription factor Nrf2 and heme oxygenase-1. Therefore, a RES-loaded LCS is a promising new therapeutic approach to mitigate skin photodamage.

Topics: Animals; Antioxidants; Benzothiazoles; Edema; Female; Glutathione; Glutathione Peroxidase; Glutathione Peroxidase GPX1; Heme Oxygenase-1; Humans; Inflammation; Interleukin-10; Matrix Metalloproteinase 9; Mice; Mice, Hairless; Molecular Structure; Oxidative Stress; Resveratrol; Skin; Stilbenes; Sulfonic Acids; Superoxides; Ultraviolet Rays

Inflammation derived from macrophages activation leads to various diseases. Synthetic modifications of resveratrol have been shown to have better anti-inflammatory activities. In this study, croton oil-induced mouse ear edema and lipopolysaccharides (LPS)-stimulated RAW264.7 macrophages were used to evaluate the anti-inflammatory effects of WL-09-5, a derivative of resveratrol. Furthermore, the activation of NF-κB was determined. Results showed that WL-09-5 significantly reduced the croton oil-induced ear edema, scavenged NO and ROS production, and reduced the levels of TNF-α, IL-6, and IL-1β. Furthermore, WL-09-5 may significantly inhibit the translocation of NF-κB in macrophage cells stimulated by LPS in a dose-dependent manner, which is a potent mechanism of its anti-inflammatory effects. In conclusion, WL-09-5 is an underlying candidate for inflammatory diseases that need further investigations.

Topics: Animals; Anti-Inflammatory Agents; Cyclooxygenase 2; Cytokines; Dinoprostone; Edema; Inflammation; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Macrophages; Mice; Molecular Structure; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Resveratrol; Signal Transduction; Stilbenes; Tumor Necrosis Factor-alpha

Inflammatory response plays an important role not only in the normal physiology, but also in the pathology of certain diseases such as cancers. In our previous study, we found a novel derivative of pterostilbene (PTER), to be an effective inducer of apoptosis in human breast and prostate cancer cells affecting various cellular targets. Herein, we further attempted to investigate its anti-inflammatory potential followed by its probable mode of action. The newly developed compound was tested for its anti-inflammatory actions in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages and carrageenan induced rat paw edema models. Our data showed that the derivative inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as the downstream products like nitric oxide (NO) and PGE2, at much lower doses as compared to PTER. This effect was found to be associated with the inhibition of phosphorylation/degradation of IκB-α and nuclear translocation of the p-NFκB p65. Moreover, inhibition of mitogen-activated protein kinases (MAPKs) and activator protein-1 (AP-1) was also observed. In addition, the newly developed compound also reduced the paw edema, the tissue content of NO, PGE2 and expression of iNOS and COX-2 proteins within the tissues after λ-carrageenan stimulation. Taken together, our findings provide the possibility that the PTER derivative might have enhanced cancer chemopreventive potential based on its stronger anti-NFκB and anti-inflammatory activities as compared to its natural counterpart, i.e., PTER. Thus, this compound can be used towards the development of an effective anti-inflammatory agent.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Carrageenan; Cyclooxygenase 2; Edema; Foot; I-kappa B Proteins; Lipopolysaccharides; Mice; Mitogen-Activated Protein Kinases; Nitric Oxide Synthase Type II; Phosphorylation; Rats; RAW 264.7 Cells; Stilbenes; Transcription Factor AP-1; Transcription Factor RelA

Pomegranate seed oil (PSO) has diverse bioactivities. It was hyphothesized that if PSO were employed to construct a trans-resveratrol-loaded self-nanoemulsifying drug delivery system (RES SNEDDS-PSO), not only could PSO serve as an oil phase but also exert synergistic effects with resveratrol to yield better therapeutic outcomes. In this study, we prepared RES SNEDDS-PSO for the first time to validate that hypothesis. The anti-inflammatory and anticancer activities of RES SNEDDS-PSO were compared with another SNEDDS composed of oil phase isopropyl palmitate (RES SNEDDS-IP). The results showed that upon exposure to a 10-fold amount of water, RES SNEDDS-PSO was converted into nanoemulsions with a mean size of 44 nm. Nanoemulsions enhanced the water solubility of resveratrol by 20-fold, significantly improved resveratrol stability in intestinal fluid, and slowed the decomposition of resveratrol in water by 1-fold. An in vivo anti-infection test showed that the degree of inflammatory swelling in mice given RES SNEDDS-PSO was only 60 and 76% that of the group fed with RES SNEDDS-IP at doses of 10 and 20 mg/kg, respectively. An in vitro anticancer study showed that the inhibitory rate of RES SNEDDS-PSO against MCF-7 breast cancer cells was 2.03- and 1.24-fold that of RES SNEDDS-IP at a concentration of 12.5 and 25 µg/mL, respectively. This study demonstrated that the newly developed SNEDDS may be a prospective formulation in the functional food and clinical fields.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Carrageenan; Cell Survival; Drug Delivery Systems; Drug Synergism; Edema; Gastric Juice; Humans; Intestinal Secretions; Lythraceae; MCF-7 Cells; Mice; Plant Oils; Resveratrol; Seeds; Solubility; Stilbenes; Water

The aim of this study was to improve the anti-inflammatory activities of apigenin through co-treatment with resveratrol as a bioenhancer of apigenin. RAW 264.7 cells pretreated with hepatic metabolites formed by the co-metabolism of apigenin and resveratrol (ARMs) in HepG2 cells were stimulated with lipopolysaccharide (LPS). ARMs prominently inhibited (p < 0.05) the production of nitric oxide (NO), prostaglandin E₂ (PGE₂), interleukin (IL)-1β, IL-6 and TNF-α. Otherwise no such activity was observed by hepatic metabolites of apigenin alone (AMs). ARMs also effectively suppressed protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Co-administration of apigenin (50 mg/kg) and resveratrol (25 mg/kg) also showed a significant reduction of carrageenan-induced paw edema in mice (61.20% to 23.81%). Co-administration of apigenin and resveratrol led to a 2.39 fold increase in plasma apigenin levels compared to administration of apigenin alone, suggesting that co-administration of resveratrol could increase bioavailability of apigenin. When the action of resveratrol on the main apigenin metabolizing enzymes, UDP-glucuronosyltransferases (UGTs), was investigated, resveratrol mainly inhibited the formation of apigenin glucuronides by UGT1A9 in a non-competitive manner with a Ki value of 7.782 μM. These results suggested that resveratrol helps apigenin to bypass hepatic metabolism and maintain apigenin's anti-inflammatory activities in the body.

Topics: Animals; Anti-Inflammatory Agents; Apigenin; Carrageenan; Cyclooxygenase 2; Dinoprostone; Drug Synergism; Edema; Glucuronosyltransferase; Hep G2 Cells; Humans; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Male; Mice; Mice, Inbred ICR; Nitric Oxide; Nitric Oxide Synthase Type II; RAW 264.7 Cells; Resveratrol; Stilbenes; Tumor Necrosis Factor-alpha

This study investigates the anti-inflammatory effects of a stilbene compound, desoxyrhapontigenin, which was isolated from Rheum undulatum. To determine the anti-inflammatory effects of this compound, lipopolysaccharide (LPS)-induced RAW 264.7 macrophages were treated with different concentrations of six stilbene derivatives. The results indicated that compared with other stilbene compounds, desoxyrhapontigenin (at 10, 30 and 50μM concentrations) significantly inhibited nitric oxide (NO) production, nuclear factor kappa B (NF-κB) activation, the protein expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. Therefore, the anti-inflammatory mechanism of desoxyrhapontigenin was investigated in detail. The results of this investigation demonstrated that desoxyrhapontigenin suppressed not only LPS-stimulated pro-inflammatory cytokine secretions, including the secretions of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), but also PGE2 release. As assayed by electrophoretic mobility shift assays (EMSAs), desoxyrhapontigenin also produced the dose-dependent inhibition of the LPS-induced activation of NF-κB and AP-1. Moreover, desoxyrhapontigenin inhibited the protein expression of myeloid differentiation primary response gene 88 (MyD88), IκB kinase (IKK) phosphorylation and the degradation of IκBα. Activations of p-JNK1 and p-Akt were also significantly inhibited, and phosphorylation of p38 and ERK was down-regulated. A further study revealed that desoxyrhapontigenin (5 and 25mg/kg, i.p.) reduced paw swelling in carrageenan-induced acute inflammation model in vivo. On the whole, these results indicate that desoxyrhapontigenin showed anti-inflammatory properties by the inhibition of iNOS and COX-2 expression via the down-regulation of the MAPK signaling pathways and the inhibition of NF-κB and Akt activation.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Cell Line; Cyclooxygenase 2; Cytokines; Disease Models, Animal; Edema; Gene Expression Regulation; Inflammation Mediators; Lipopolysaccharides; Macrophages; Male; MAP Kinase Signaling System; Mice; Mice, Inbred ICR; NF-kappa B; Nitric Oxide Synthase Type II; Rheum; Rhizome; Stilbenes; Transcription Factor AP-1

To explore the effects of activating silent information regulator 1 (SIRT1) on early myocardial damage in severely burned rats.. Twenty-four healthy male SD rats were divided into sham injury group (SI), scald group (S), and resveratrol (RSV) treatment group (RT) according to the random number table, with 8 rats in each group. Rats in groups S and RT were inflicted with 30% TBSA full-thickness scald on the back by immersing in 95 °C water for 18 s. Immediately after injury, rats in group S were intraperitoneally injected with 10 mL normal saline (50 mL/kg) and those in group RT with 10 mL normal saline (50 mL/kg)+10 µL RSV in the concentration of 1 g/mL (50 mg/kg). Backs of rats in group SI were immersed in 20 °C room temperature water for 18 s to simulate the scald process. Heart tissues and aorta abdominalis blood samples were collected at post injury hour (PIH) 6. The histomorphology of heart tissues was observed with HE staining. The serum contents of creatine kinase (CK) and lactate dehydrogenase (LDH) were determined with ELISA. The protein expressions of SIRT1 and caspase-3 and mRNA expressions of SIRT1, caspase-3, IL-1β, and TNF-α in heart tissue specimens were determined with Western blotting and real-time fluorescent quantitative RT-PCR (with protein level denoted as gray value). Data were processed with one-way analysis of variance and LSD- t test.. (1) In group SI, myocardial fibers were in irregularly cylindrical shape, neatly arranged, and the transverse striation were distinct. In group S, myocardial interstitial edema, disorder of myocardial fiber arrangement, and cytoplasm destruction were observed. In group RT, the degrees of myocardial interstitial edema, disorder of myocardial fiber arrangement, and cytoplasm destruction were alleviated in comparison with those of group S. (2) The serum contents of CK and LDH of rats in group S were respectively (2 385 ± 712) and (2 551 ± 196) U/L, which were significantly higher than those in the group SI [(290 ± 59) and (759 ± 60) U/L, with t values respectively 9.466 and 25.452, P values below 0.01]. The serum contents of CK and LDH of rats in group RT were respectively (1 336 ± 149) and (2 209 ± 133) U/L, which were significantly lower than those of group S (with t values respectively -4.506 and -4.860, P values below 0.01). (3) The protein expressions of SIRT1 and caspase-3 in heart tissue of rats in group S were respectively 0.47 ± 0.11 and 0.48 ± 0.12, which were significantly higher than those in group SI [0.18 ± 0.06 and 0.09 ± 0.05, with t values respectively 4.813 and 9.014, P values below 0.01]. The protein expression of SIRT1 in heart tissue of rats in group RT was 0.74 ± 0.18, which was significantly higher than that of group S (t = 4.561, P < 0.01); the protein expression of caspase-3 in heart tissue of rats in group RT was 0.21 ± 0.08, which was significantly lower than that of group S (t = -6.239, P < 0.01). (4) The mRNA expressions of SIRT1, caspase-3, IL-1β, and TNF-α in heart tissue of rats in group S were respectively 2.33 ± 0.24, 1.96 ± 0.20, 2.46 ± 0.21, 1.89 ± 0.37, which were significantly higher than those in group SI (1.00 ± 0.07, 1.00 ± 0.06, 1.00 ± 0.08, 1.00 ± 0.09, with t values respectively 14.961, 12.823, 18.559, 6.679, P values below 0.01). The mRNA expression of SIRT1 in heart tissue of rats in group RT was 2.89 ± 0.31, which was significantly higher than that of group S (t = 3.997, P < 0.01). The mRNA expressions of caspase-3, IL-1β, and TNF-α in heart tissue of rats in group RT were respectively 1.31 ± 0.08, 1.64 ± 0.09, 1.25 ± 0.08, which were significantly lower than those of group S (with t values respectively -8.264, -10.245, -4.818, P values below 0.01).. The expression of SIRT1 in heart tissue is upregulated in the early stage of severely burned rats. Activation of SIRT1 by RSV can alleviate myocardial tissue injury and reduce apoptosis of cardiac myocytes and secretion of IL-1β and TNF-α.

Topics: Animals; Antioxidants; Apoptosis; Burns; Caspase 3; Edema; Interleukin-1beta; Male; Myocardium; Myocytes, Cardiac; Rats; Resveratrol; RNA, Messenger; Serum; Sirtuin 1; Stilbenes; Tumor Necrosis Factor-alpha; Up-Regulation

Resveratrol is a phytoalexin abundantly found in red grape skin and is effective in antitumor and antiinflammation associated with immune responses. This study investigated whether resveratrol suppressed immunoglobulin (Ig)E-mediated allergic responses and passive cutaneous anaphylaxis (PCA) in rat RBL-2H3 mast cells and in BALB/c mice. The release of β-hexosaminidase and histamine was enhanced in mast cells sensitized with anti-dinitrophenyl (DNP)-IgE and subsequently stimulated by DNP-human serum albumin (HSA), indicative of mast cell degranulation. When mast cells were pretreated with nontoxic resveratrol at 1-25 μmol/L, such induction was dose dependently diminished. Spleen tyrosine kinase (Syk) and phospholipase Cγ (PLCγ) of sensitized mast cells were activated by stimulation with DNP-HSA antigen, which was dampened by ≥5 μmol/L resveratrol. The phosphorylation of protein kinase C (PKC)μ and PKCθ was attenuated by administering resveratrol to DNP-HSA-exposed mast cells, whereas quiescent PKCζ/λ in sensitized cells was dose-dependently activated by resveratrol. Male BALB/c mice were sensitized for 24 h with DNP-IgE and orally administered with resveratrol 1 h before the DNP-HSA challenge. The histamine concentration was enhanced in sensitized mice challenged to DNP-HSA, which was reversed by administration of 10 mg/kg resveratrol. Additionally, it encumbered the tissue activation of Syk, PLCγ, and PKCμ in antigen-exposed mice. Resveratrol decreased IgE-mediated PCA and alleviated allergic edema of mouse ear and dorsal skin. Mast cell degranulation and allergic inflammation, accompanying the induction of monocyte chemotactic protein-1 and macrophage inflammatory protein-2, were inhibited by supplementing resveratrol to antigen-challenged mice. Resveratrol inhibited mast cell-derived, immediate-type allergic reactions, and these responses of resveratrol suggest possible therapeutic strategies in preventing allergic inflammatory diseases.

Topics: Anaphylaxis; Animals; Basophils; beta-N-Acetylhexosaminidases; CD24 Antigen; Chemokine CCL2; Chemokine CXCL2; Dietary Supplements; Dinitrophenols; Dose-Response Relationship, Drug; Edema; Histamine; Histamine Release; Immunoglobulin E; Inflammation; Intracellular Signaling Peptides and Proteins; Male; Mast Cells; Mice; Mice, Inbred BALB C; Passive Cutaneous Anaphylaxis; Phospholipase C gamma; Phosphorylation; Phytotherapy; Plant Extracts; Protein-Tyrosine Kinases; Rats; Resveratrol; Serum Albumin; Skin; Stilbenes; Syk Kinase; Vitis

KYKZL-1, a newly synthesized compound with COX/5-LOX dual inhibition, was subjected to the anti-inflammatory activity test focusing on its modulation of inflammatory mediators as well as intracellular MAPK and NF-κB signaling pathways. In acute ear edema model, pretreatment with KYKZL-1 (p.o.) dose-dependently inhibited the xylene-induced ear edema in mice with a higher inhibition than diclofenac. In a three-day TPA-induced inflammation, KYKZL-1 also showed significant anti-inflammatory activity with inhibition ranging between 20% and 64%. In gastric lesion test, KYKZL-1 elicited markedly fewer stomach lesions with a low index of ulcer as compared to diclofenac in rats. In further studies, KYKZL-1 was found to significantly inhibit the production of NO, PGE2, LTB4 in LPS challenged RAW264.7, which is parallel to its attenuation of the expression of iNOS, COX-2, 5-LOX mRNAs or proteins and inhibition of phosphorylation of p38 and ERK MAPKs and activation of NF-κB. Taken together, our data indicate that KYKZL-1 comprises dual inhibition of COX and 5-LOX and exerts an obvious anti-inflammatory activity with an enhanced gastric safety profile via simultaneous inhibition of phosphorylation of p38 and ERK MAPKs and activation of NF-κB.

Topics: Animals; Anti-Inflammatory Agents; Blotting, Western; Cell Line; Cyclooxygenase Inhibitors; Dinoprostone; Edema; Indicators and Reagents; Inflammation Mediators; Leukotriene B4; Lipopolysaccharides; Lipoxygenase Inhibitors; Male; MAP Kinase Signaling System; Mice; Mice, Inbred ICR; NF-kappa B; Nitric Oxide; Phenylpropionates; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Stilbenes; Stomach Ulcer; Xylenes

We hypothesized that resveratrol administration would reverse sepsis-dependent downregulation of peroxisome proliferator activated receptor-γ coactivator 1α, preserve mitochondrial integrity, and rescue animals from sepsis-induced myocardial failure.. Teaching hospital research laboratory.. Cecal ligation and puncture in mice was performed to induce sepsis. Mice that underwent cecal ligation and puncture were randomly assigned to receive resveratrol (30 mg/kg or 60 mg/kg) or vehicle 1 mL sodium chloride 0.9% subcutaneously in the scruff of the neck directly after surgery and at 16, 24, and 40 hrs, respectively.. Forty-eight hrs after cecal ligation and puncture, cardiac performance was established using echocardiography. Mitochondrial integrity was evaluated with electron microscopy, and changes in gene expression were evaluated with microarray analysis. Survival at 48 hrs was just under 50% and comparable between groups. Myocardial contractile function significantly improved after resveratrol treatment. Resveratrol-treated mice developed focal areas of edema, whereas vehicle-treated mice developed significant, diffuse myocardial edema. Electron microscopy revealed widespread swollen mitochondria with ruptured outer membranes, autophagosomes, and vacuolation of the internal compartment, which were significantly attenuated in resveratrol-treated animals. Resveratrol treatment significantly increased cardiac expression of peroxisome proliferator-activated receptor-γ coactivator 1a. Microarray analysis revealed that resveratrol treatment resulted in upregulation of the peroxisome proliferator-activated receptor-γ coactivator gene set containing genes known to be regulated by this transcriptional coactivator. Our data strongly suggest that administration of resveratrol modulates bioenergy metabolism, substrate utilization, oxidative stress, and detoxification pathways associated with both mitochondrial and cardiac pathological conditions, but does not alter mortality from sepsis.. The salutary effects of resveratrol on cecal ligation and puncture-induced myocardial dysfunction are associated with increased peroxisome proliferator-activated receptor-γ coactivator 1a abundance and function. Preservation of myocardial energy production capacity, prevention of secondary injury, mitigation of inflammation, and reversal of sepsis-induced myocardial remodeling are likely to underlie its beneficial effects. This however, does not result in improved survival.

Topics: Animals; Cardiomyopathies; Cecum; Down-Regulation; Edema; Gene Expression; Heart Failure; Ligation; Male; Mice; Mice, Inbred C57BL; Mitochondria, Heart; Myocardial Contraction; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Random Allocation; Resveratrol; Sepsis; Stilbenes; Trans-Activators; Transcription Factors; Vasodilator Agents

This study examined the analgesic and anti-inflammatory actions of cis-mulberroside A isolated from Ramulus mori in several models of inflammatory pain in mice. Cis-mulberroside A (25 and 50mg/kg) given by p.o. route 30 min before challenge produced a dose-dependent inhibition of the acetic acid-induced pain and Evans blue leakage in mice. In addition, this compound exhibited significant systemic anti-inflammatory activity in carrageenan-induced mouse paw edema in a concentration-related manner (33.1-68.5% inhibition), and similar results were achieved in formalin test. Suppressive effects of cis-mulberroside A on the production of NO and expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated macrophages were also assessed. Collectively, cis-mulberroside A showed high analgesic and anti-inflammatory activities. The above results will be the supporting evidence for the potential anti-rheumatoid activity of R.mori in Chinese traditional medicine.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Cell Line; Disaccharides; Dose-Response Relationship, Drug; Edema; Evans Blue; Formaldehyde; Inflammation; Lipopolysaccharides; Macrophages; Male; Mice; Mice, Inbred ICR; Moraceae; Nitric Oxide; Nitric Oxide Synthase Type II; Pain; Phytotherapy; Plant Extracts; Plant Stems; Stilbenes

To determine whether ischemic preconditioning (IP) affects the development of edematous cerulein-induced pancreatitis and to assess the role of cyclooxygenase-1 (COX-1), COX-2, and heat shock protein 70 (HSP 70) in this process.. In male Wistar rats, IP was performed by clamping of celiac artery (twice for 5 min at 5-min intervals). Thirty minutes after IP or sham operation, acute pancreatitis was induced by cerulein. Activity of COX-1 or COX-2 was inhibited by resveratrol or rofecoxib, respectively (10 mg/kg).. IP significantly reduced pancreatic damage in cerulein-induced pancreatitis as demonstrated by the improvement of pancreas histology, reduction in serum lipase and poly-C ribonuclease activity, and serum concentration of pro-inflammatory interleukin (IL)-1beta. Also, IP attenuated the pancreatitis-evoked fall in pancreatic blood flow and pancreatic DNA synthesis. Serum level of anti-inflammatory IL-10 was not affected by IP. Cerulein-induced pancreatitis and IP increased the content of HSP 70 in the pancreas. Maximal increase in HSP 70 was observed when IP was combined with cerulein-induced pancreatitis. Inhibition of COXs, especially COX-2, reduced the protective effect of IP in edematous pancreatitis.. Our results indicate that IP reduces pancreatic damage in cerulein-induced pancreatitis and this effect, at least in part, depends on the activity of COXs and pancreatic production of HSP 70.

Topics: Animals; Ceruletide; Cyclooxygenase Inhibitors; Edema; HSP70 Heat-Shock Proteins; Interleukin-1; Interleukin-10; Ischemic Preconditioning; Lactones; Male; Pancreatitis; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Wistar; Resveratrol; Stilbenes; Sulfones

Seventeen novel resveratrol derivatives were synthesized. Their anti-inflammatory activities were tested on xylene-induced mouse ear edema. The pharmacological results showed that some compounds have potent anti-inflammatory activities.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzene Derivatives; Ear, External; Edema; Indicators and Reagents; Mannich Bases; Mice; Pyridines; Resveratrol; Spectrometry, Mass, Electrospray Ionization; Stilbenes

Carcinogenesis is a complex process and at least 3 stages, including initiation, promotion, and progression, have been proposed in the process of carcinogenesis. Resveratrol has attracted considerable attention due to its low toxicity and unique chemical structure. This study was designed to test chemopreventive effect of resveratrol to cancer using various animal models.. Ames assay and micronucleus formation assay were used to test the antimutagenic activities of resveratrol. Croton oil-induced enhancement of ornithine decarboxylase (ODC) activities of dorsal epidermis cells in mouse and mouse ear edema model were used to investigate the anti-promotion effect of resveratrol. In addition,7,12-dimenthylbenz[a]anthracene (DMBA)/croton oil-induced mouse skin tumor model was used to evaluate chemopreventive effect of resveratrol to cancer in vivo.. In Ames test,100 microg/plate of resveratrol exhibited 42.2% of inhibition on the reversion of Salmonella typhimurium TA100 induced by methylmethansulfonate, and 200 microg/plate of resveratrol exhibited 91.8% of inhibition on the reversion induced by benzopyrene. Pretreatment of resveratrol prevented cyclophosphamide (CTX)-induced micronucleus formation of polychromatic erythrocytes of mice bone marrow in dose-dependent manner. Mice treated with 30 mg/kg of resveratrol for 6 days before croton oil exposure have palliative ear edema. Treatment of 180 mg/kg resveratrol for 3 days caused 69.3% decrease of ODC activities in croton oil-induced dorsal epidermis. It was shown that resveratrol could inhibit DMBA/croton oil-induced mouse skin papilloma, which includes prolonging the latent period of tumor occurrence, decreasing the incidence of papilloma, and reducing tumor number per mouse in dose-dependent manner.. Resveratrol has the ability of anti-mutation and anti-promotion of cancer and merit further studies as a potential cancer chemopreventive agent.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Antimutagenic Agents; Croton Oil; Ear Diseases; Edema; Epithelial Cells; Female; Male; Mice; Mice, Inbred ICR; Micronucleus Tests; Mutagenicity Tests; Ornithine Decarboxylase; Papilloma; Resveratrol; Salmonella typhimurium; Skin Neoplasms; Stilbenes

To study the effects of resveratrol (Res) on secondary spinal cord edema, the activity of lactate dehydrogenase (LDH), Na+, K+-ATPase, and malondialdehyde (MDA) content in experimental spinal cord injured (SCI) rats.. The weight-dropping method was used to produce the experimental SCI in adult rats. Res ( 50, 100 mg/kg) and methylprednisolone (MPSS) 100 mg/kg were injected ip immediately after the induction of SCI. The effects of Res on edema, LDH, Na+, K+-ATPase, and MDA were determined at 1 h, 24 h, and 48 h after SCI compared with MPSS. The electron microscope was employed to investigate the ultrastructural effects of Res on axons, neurons, and subcellular organelles after SCI.. Res obviously inhibited the secondary spinal cord edema with the most remarkable suppressing rate by 11.5 % at 48 h. Res significantly suppressed the activities of the lactate dehydrogenase with the highest suppressing rate > 40 % at 24 h. Res markedly improved the Na+, K+-ATPase activities that were promoted to the biggest extent of 60 % at 48 h. At the same time, Res (50 and 100 mg/kg) obviously reduced MDA production in the injured spinal cord tissue in comparison with the SCI model, the most remarkable effect of Res was detected at 48 h with the inhibitory rate >40 %. The ultrastructural findings suggested that SCI caused profound spinal cord damage, which could be protected or improved by injection of Res and MPSS.. Both Res and MPSS effectively protected the spinal cord from secondary spinal cord injures. But the effects of Res 50 and 100 mg/kg were stronger in improving the energy metabolism system and inhibiting the lipid peroxidation in the local injured spinal cord after SCI than MPSS at the dose of 100 mg/kg. Res might have greatly potent therapeutic effects on SCI.

Topics: Acute Disease; Animals; Edema; Female; L-Lactate Dehydrogenase; Male; Malondialdehyde; Methylprednisolone; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Resveratrol; Sodium-Potassium-Exchanging ATPase; Spinal Cord Injuries; Stilbenes

To investigate the expression of matrix metalloproteinase-9 (MMP-9) in mouse ears induced with croton oil and the inhibitory effect of dexamethasone, indomethacin and resveratrol on MMP-9 expression, and further explore the relationship between anti-inflammation and MMP-9 inhibition of these three medicines.. Immuno-histochemistry was used to detect the expression of MMP-9 in mouse ears. Expression of MMP-9 in U937 cells was analyzed by gelatin zymography.. Mouse ear edema induced with croton oil was inhibited significantly by dexamethasone and indomethacin at the dose of 10 mg.kg-1 and resveratrol at 50 mg.kg-1 administered subcutaneously. The inhibitory rate was 76.2% (P < 0.001), 56.7% (P < 0.001) and 36.9% (P < 0.001) respectively. The MMP-9 expression increased in mouse ears induced with croton oil and inhibited by dexamethasone, indomethacin and resveratrol at above doses. Gelatin zymography results showed that MMP-9 expression in U937 cells increased significantly after exposed to PMA at 1 x 10(-8) mol.L-1 (P < 0.001); MMP-9 expression induced with phorbol myristate acetate(PMA) was inhibited by dexamethasone at 1 x 10(-9), 1 x 10(-7) and 1 x 10(-5) mol.L-1, indomethacin at 1 x 10(-6) and 1 x 10(-5) mol.L-1 and resveratrol at 1 x 10(-6) and 1 x 10(-5) mol.L-1.. The inhibition of MMP-9 expression may be one of the anti-inflammatory mechanisms of dexamethasone, indomethacin and resveratrol.

Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Croton Oil; Dexamethasone; Ear Diseases; Edema; Humans; Indomethacin; Male; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Mice; Mice, Inbred ICR; Random Allocation; Resveratrol; Stilbenes; U937 Cells

The anti-inflammatory activity of alpha-viniferin, a trimer of resveratrol, has been demonstrated in an animal model of carrageenin-induced paw edema, and inhibitory effects of the compound on cyclooxygenase (COX) and inducible nitric oxide synthase (iNOS) have been investigated in order to understand the mode of the observed action. alpha-Viniferin at doses > 30 mg/kg ( p. o.) or > 3 mg/kg ( i. v.) showed significant anti-inflammatory activity on carrageenin-induced paw edema in mice. alpha-Viniferin showed an inhibitory effect with an IC (50) value of 4.9 microM on COX-2 activity but a very weak inhibitory effect with 55.2 +/- 2.1 % of the control (100 %) at 100 microM on COX-1 activity. alpha-Viniferin at doses of 3 microM to 10 microM inhibited the synthesis of COX-2 transcript in lipopolysaccharide (LPS)-activated murine macrophages Raw264.7. alpha-Viniferin showed an IC50 value of 2.7 microM on nitric oxide (NO) production in LPS-activated Raw264.7 cells when alpha-viniferin and LPS were treated simultaneously, but did not inhibit the NO production when alpha-viniferin was treated at 12 h after LPS stimulation. alpha-Viniferin inhibited synthesis of iNOS transcript with an IC50 value of 4.7 microM. Consequently, the inhibitory effect of alpha-viniferin on the release of prostanoids and NO could play an important role to show anti-inflammatory action.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzofurans; Caragana; Carrageenan; Cell Line; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; DNA Primers; Dose-Response Relationship, Drug; Edema; Inhibitory Concentration 50; Injections, Intravenous; Isoenzymes; Macrophages; Male; Mice; Mice, Inbred ICR; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Phytotherapy; Prostaglandin-Endoperoxide Synthases; Reverse Transcriptase Polymerase Chain Reaction; Stilbenes

The antioxidative effects of mulberroside A and oxyresveratrol obtained from Mori Cortex were examined. Mulberroside A and oxyresveratrol showed an inhibitory effect against FeSO4/H2O2-induced lipid peroxidation in rat microsomes and a scavenging effect on 1,1-diphenyl-2-picrylhydrazyl radical. The anti-inflammatory effects of mulberroside A and oxyresveratrol using the carrageenin-induced model of inflammation were investigated in rats. Mulberroside A and oxyresveratrol significantly reduced paw edema. To investigate the mechanism of the anti-inflammatory action of these compounds, we examined the effects of oxyresveratrol on lipopolysaccharide (LPS)-induced responses in murine macrophage cell line RAW 264.7. Exposure of LPS-stimulated cells to oxyresveratrol inhibited nitrite accumulation in the culture medium. Oxyresveratrol also inhibited the LPS-stimulated increase of inducible nitric oxide synthase (iNOS) expression in a concentration-dependent manner; however, it had little effect on iNOS enzyme activity, suggesting that the inhibitory activity of oxyresveratrol is mainly due to the inhibition of iNOS expression rather than iNOS enzyme activity. Oxyresveratrol significantly inhibited LPS-evoked nuclear translocation of NF-kappaB and cyclooxygenase-2 (COX-2) activity in RAW 264.7 cells. The results suggest that the anti-inflammatory properties of oxyresveratrol might be correlated with inhibition of the iNOS expression through down-regulation of NF-kappaB binding activity and significant inhibition of COX-2 activity.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cells, Cultured; Dinoprostone; Disaccharides; Edema; Inflammation; Lipid Peroxidation; Male; Microsomes, Liver; Morus; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Phytotherapy; Plant Extracts; Plant Preparations; Rats; Rats, Sprague-Dawley; Stilbenes

The effect of resveratrol, an aryl hydrocarbon receptor (AhR) antagonist, known to inhibit inducible cyclooxygenase-2 (COX2) and its transcription were examined in a model of hyperalgesia induced by carrageenan in the rat. Pretreatment with resveratrol did not reverse swelling and edema, but reversed the hyperalgesia induced by local tissue injury provoked by carrageenan. This reversal, occurring at resveratrol concentrations as low as 2 mg/kg, lasted for at least 48 hours. The link with COX2 activity inhibition and COX2 gene transcription, as well as a potential AhR inhibitory effect, remain to be established.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Edema; Foot; Hindlimb; Hyperalgesia; Isoenzymes; Kinetics; Male; Pain Measurement; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; Receptors, Aryl Hydrocarbon; Resveratrol; Stilbenes; Vocalization, Animal