Antinociceptive, anti-inflammatory and gastroprotective effects of a hydroalcoholic extract from the leaves of Eugenia punicifolia (Kunth) DC. in rodents

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Involvement of AMPK, IKβα-NFκB and eNOS in the sildenafil anti-inflammatory mechanism in a demyelination model

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Anti-inflammatory effects of Brazilian ginseng (Pfaffia paniculata) on TNBS-induced intestinal inflammation: experimental evidence

Inflammatory bowel disease (IBD) is a chronic, relapsing, idiopathic inflammation of the gastrointestinal tract. Clinical studies suggest that the initiation of IBD is multifactorial, involving genetics, the immune system and environmental factors, such as diet, drugs and stress. Pfaffia paniculata is an adaptogenic medicinal plant used in Brazilian folk medicine as an anti-stress agent. Thus, we hypothesised that the P. paniculata enhances the response of animals subjected to colonic inflammation. Our aim was to investigate the intestinal anti-inflammatory activity of P. paniculata in rats before or after induction of intestinal inflammation using trinitrobenzenesulfonic acid (TNBS). The animals were divided into groups that received the vehicle, prednisolone or P. paniculata extract daily starting 14days before or 7days after TNBS induction. At the end of the procedure, the animals were killed and their colons were assessed for the macroscopic damage score (MDS), extent of the lesion (EL) and weight/length ratio, myeloperoxidase (MPO) activity and glutathione (GSH), cytokines and C-reactive protein (CRP) levels. Histological evaluation and ultrastructural analysis of the colonic samples were performed. Treatment with the 200mg/kg dose on the curative schedule was able to reduce the MDS and the EL. In addition, MPO activity was reduced, GSH levels were maintained, and the levels of pro-inflammatory cytokines and CRP were decreased. In conclusion, the protective effect of P. paniculata was related to reduced oxidative stress and CRP colonic levels, and due to immunomodulatory activity as evidenced by reduced levels of IL-1β, INF-γ, TNF-α and IL-6.

Anti-hyperalgesic and anti-inflammatory activity of Alternanthera maritima extract and 2″-O-α-L-rhamnopyranosylvitexin in mice

Alternanthera maritima are used in Brazilian popular medicine for the treatment of inflammatory and infectious diseases. Species of Alternanthera have demonstrated biological activities in previous scientific studies. The aim of this study was to determine whether the ethanol extract of the aerial parts of A. maritima (EEAM) and the isolated compound 2″-O-α-L-rhamnopyranosyl-vitexin inhibit mechanical hyperalgesia and parameters of inflammation in mice. The oral administration of EEAM significantly inhibited carrageenan (Cg)-induced paw edema and reduced leukocyte migration into the pleural cavity. 2″-O-α-L-rhamnopyranosylvitexin significantly inhibited paw edema and reduced both leukocyte migration and the leakage of protein into the pleural cavity. Both EEAM and 2″-O-α-L-rhamnopyranosylvitexin significantly prevented the Cg-induced hyperalgesia. Local administration of 2″-O-α-L-rhamnopyranosylvitexin significantly prevented the Cg- and tumor necrosis factor (TNF)-induced hyperalgesia. In conclusion, this study demonstrated that EEAM is an anti-inflammatory and anti-hyperalgesic agent, and the results suggested that 2″-O-α-L-rhamnopyranosylvitexin is responsible for the effects of EEAM and the mechanism involves the TNF pathway.

Experimental evidence of MAP kinase gene expression on the response of intestinal anti-inflammatory drugs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Experimental evidence of heparanase, Hsp70 and NF-κB gene expression on the response of anti-inflammatory drugs in TNBS-induced colonic inflammation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antitumour and anti-inflammatory effects of Palladium (II) complexes on Ehrlich Tumour

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Beneficial effects of diclofenac therapy on serum lipids, oxidized low-density lipoprotein and antioxidant defenses in rats

To study the effects of diclofenac, a nonselective nonsteroidal anti-inflammatory drug (NSAID), on lipid profile, oxidized low-density-lipoprotein (Ox-LDL), serum antioxidant defenses and markers of oxidative stress, male Wistar rats were divided into two groups (n = 10): (C) receiving intramuscularly a single daily dose of saline (NaCl 0.9%), and (AI) receiving intramuscularly a single daily dose of 10 mg/kg diclofenac sodium (C14H10C12NNaO2). After 28 days diclofenac-treated rats had lower Ox-LDL, apoprotein B (apo-B), apo-B/LDL-cholesterol and lipid hydroperoxide than C. Total antioxidant substances and superoxide dismutase were increased in diclofenac-treated rats, while no significant changes were observed in catalase, glutathione peroxidase and nitric oxide. A perincubation test done to examine the possibility of mechanism-based activation showed that diclofenac had no effect on maximal superoxide dismutase velocity, but significantly reduced the Michaelis-Menten (K-M) constant, indicating that diclofenac induced SOD activation increasing substrate linkage affinity to the enzyme-catalytic site. In conclusion, diclofenac had beneficial effects decreasing Ox-LDL and improving antioxidant defense. It appears that the application of this agent may be feasible and beneficial for serum antioxidant protection, which certainly would bring new insights on dyslipidemia control. (C) 2008 Elsevier B.V. All rights reserved.

Celecoxib treatment does not alter recruitment and activation of osteoclasts in the initial phase of experimental tooth movement

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Brazilian Medicinal Plant Acts on Prostaglandin Level and Helicobacter pylori

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Determination of 5-aminosalicylic acid in pharmaceutical formulations by square wave voltammetry at pencil graphite electrodes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Lipoperoxidation and cyclooxygenases 1 and 2 inhibitory compounds from Iryanthera juruensis

Plants from Iryanthera genus have been traditionally used as food supplements by South American Indians. The MeOH extract of leaves of Iryanthera juruensis, one of the plants endemic to the Amazon region and consumed in Brazil, and the hexane extract from its seeds inhibited lipid peroxidation (LPO) and cyclooxygenase (COX-1 and -2)) enzymes in in vitro assays. Further analyses of these extracts yielded 5-deoxyflavones (1-5) from the leaf extract and sargachromenol (6), sargaquinoic acid (7), a novel juruenolic acid (8), omega-arylalkanoic acids (9a-c), and the lignan guaiacin (10) from the seed extract. Compounds 3-5 inhibited LPO by 86%, 77%, and 88% at 10 ppm, respectively, and compounds 6 and 9a-c showed inhibition at 76% and 78% at 100 ppm, respectively. However, compounds 7 and 8 were inactive and lignan 10 exhibited LPO inhibitory activity by 99% at 100 ppm compared to commercial antioxidants butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and vitamin E. The flavones 1-5 also inhibited COX-1 and -2 enzymes by 50-65% at 100 ppm. Compound 6 showed high but nonselective inhibition of COX-1 and COX-2 enzymes, when compared to aspirin and Celebrex, a nonsteroidal anti-inflammatory drug (NSAID). Compounds 7 and 10 inhibited COX-1 by 60% and 65% and COX-2 by 37% and 18%, respectively, whereas compounds 8 and 9a-c showed little or no activity against these enzymes.

Preemptive dexamethasone and etoricoxib for pain and discomfort prevention after periodontal surgery: A double-masked, crossover, controlled clinical trial

Background: Several anti-inflammatory drugs have been used to reduce pain and discomfort after periodontal surgeries. This study evaluates the efficacy of using etoricoxib and dexamethasone for pain prevention after open-flap debridement surgery. Methods: For this prospective, double-masked, crossover, placebo-controlled, randomized clinical trial, open-flap debridement surgeries were performed on 15 patients (eight males and seven females, age range 20 to 56 years: mean age ± SD: 40 ± 9.7 years) who presented with chronic periodontitis after nonsurgical periodontal therapy at three quadrants. Each patient underwent three surgical procedures at intervals of 30 days and received one of the following premedication protocols 1-hour before surgery: group 1 = placebo, group 2 = 8 mg dexamethasone, and group 3 = 120 mg etoricoxib. Rescue medication (750 mg acetaminophen) was given to each patient who was instructed to take it when necessary. Pain intensity and discomfort were evaluated by a 101-point numeric rate scale and a four-point verbal rate scale, respectively, hourly for the first 8 hours after surgery and three times a day on the following 3 days. Results: The results demonstrate that groups 2 and 3 present reduced postoperative pain-intensity levels compared to group 1. There were statistically significant differences at the 4, 5, 6, 7, and 8 hour-periods after surgery (Friedman test; P<0.05). Furthermore, rescue-medication intake was significantly lower for groups 2 and 3 than for group 1 (analysis of variance; P<0.02). Conclusion: The adoption of a preemptive medication protocol using etoricoxib or dexamethasone may be considered effective for pain and discomfort prevention after open-flap debridement surgeries.

Caffeic Acid Phenethyl Ester: Consequences of Its Hydrophobicity in the Oxidative Functions and Cytokine Release by Leukocytes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeitos preventivos do treinamento físico na expressão das proteínas Cox-2 e Vegf de ratos tratados com dexametasona

Dexamethasone is a synthetic glucocorticoid widely used to treat allergic and inflammatory processes. This drug is used in three main situations, are used to contain acute or chronic inflammatory processes, or like immunosuppressive drug's. In these cases the patient will receive high doses for a chronic period and, therefore, has a much greater chance of adverse side effects, such as hypertension, diabetes and dyslipidemia. Dexamethasone promotes deleterious effects on the arachidonic acid pathway, when administered in high doses, because it is a potent anti-inflammatory drug. We recently demonstrated that dexamethasone significantly reduces the protein expression of vascular endothelial growth factor (VEGF) in both skeletal muscle and heart, but the mechanisms involved remain unclear. Meanwhile, exercise has been shown to be effective against high blood pressure, diabetes and dyslipidemia, promoting, among other factors, the increase in VEGF and angiogenesis. One possible explanation for these effects would be the creation of new vessels mediated by inflammation, or by the stimulation of the formation of products of the metabolism of arachidonic acid (AA), such as prostaglandin E2 (PGE2) and VEGF, by increasing the stimulation of the enzymes cyclooxygenase 1 and 2 (COX-1 and COX-2). Little is known about the preventive effects of training on the action of dexamethasone in the arachidonic acid pathway. Therefore, the aim of this study was to determine whether aerobic exercise training, performed before and concomitant treatment with dexamethasone, was able to prevent the effects of the dexamethasone in the protein expression of COX-2 and VEGF. For this, we used young Wistar rats (n = 40) which were randomly divided into 4 groups: sedentary control (SC), sedentary and treated with dexamethasone (SD), trained control (TC) and trained and treated with dexamethasone (TD). These rats performed aerobic exercise training, 60% of maximum capacity, 5