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La bacteria Helicobacter pylori (H. pylori) tiene una excelente capacidad de adaptación, supervivencia y colonización en ambientes ácidos como la mucosa gastrointestinal, provocando numerosas complicaciones como úlceras peptídicas, cánceres, gastritis y linfomas, como el linfoma MALT, siendo un B -neoplasia de células, subtipo de linfoma no Hodgkin. El objetivo de este trabajo es investigar qué relaciones existen entre la infección por H. pylori y las características y aspectos de la aparición del linfoma MALT. Este estudio se realizó a través de un levantamiento bibliográfico en las siguientes bases de datos: Biblioteca Virtual en Salud (BVS), Biblioteca Científica Electrónica en Línea (SciELO), Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS) en PubMed (Biblioteca Nacional de Medicina), con con la ayuda de los Descriptores de Ciencias de la Salud (DeCS): Helicobacter pylori, linfoma MALT y linfoma gástrico, agrupados con el operador booleano “AND” y “OR”. Los criterios de inclusión fueron artículos libres, en portugués e inglés, con un período de tiempo de 2011 a 2022. Los criterios de exclusión fueron estudios que estaban fuera del tema propuesto, repetidos, incompletos, resúmenes simples o revisiones. La recolección resultó en 112 artículos, 47 fueron duplicados y otros 65 fueron excluidos por la lectura rápida del título y resumen, quedando 30 estudios leídos en su totalidad y luego del análisis otros 18 fueron eliminados, quedando 12 artículos para componer estas investigaciones. Como resultado y conclusión de la investigación, se identificó que H. pylori provoca cambios químicos y celulares, principalmente inflamatorios, resultando en desequilibrio celular y envejecimiento, convirtiéndose en un factor predisponente para el linfoma MALT. The bacterium Helicobacter pylori (H. pylori) has an excellent ability to adapt, survive and colonize within acidic environments such as the gastrointestinal mucosa, causing numerous complications such as peptide ulcers, cancers, gastritis, and lymphomas, such as MALT lymphoma, being a B-cell neoplasm, subtype of non-Hodgkin's lymphoma. The objective of this work is to investigate what relationships exist between H. pylori infection and the characteristics and aspects of the emergence of MALT lymphoma. This study was carried out through a bibliographic survey in the following databases: Virtual Health Library (BVS), Scientific Electronic Library Online (SciELO), Latin American and Caribbean Literature on Health Sciences (LILACS) at PubMed (National Library of Medicine), with the help of the Health Sciences Descriptors (DeCS): Helicobacter pylori, MALT lymphoma and gastric lymphoma, grouped with the Boolean operator “AND” and “OR”. The inclusion criteria were free articles, in Portuguese and English, with a time frame from 2011 to 2022. The exclusion criteria were studies that were outside the proposed topic, repeated, incomplete, simple abstracts or reviews. The collection resulted in 112 articles, 47 were duplicates and another 65 were excluded by the quick reading of the title and abstract, leaving 30 studies read in full and after analysis another 18 were eliminated, leaving 12 articles to compose this research. As a result, and conclusion of the research, it was identified that H. pylori causes chemical and cellular changes, mainly inflammatory, resulting in cell imbalance and aging, making it a predisposing factor for MALT lymphoma. A bactéria Helicobacter pylori (H. pylori) possui uma capacidade exímia de se adaptar, sobreviver e se colonizar dentro de ambientes ácidos como a mucosa gastrointestinal, causando inúmeras complicações como úlceras peptídicas, cânceres, gastrite e linfomas, como o linfoma MALT, sendo uma neoplasia de células B, subtipo dos linfomas não-Hodgkin. O objetivo desse trabalho é investigar quais relações existem entre a infecção pela H. pylori com as características e aspectos do surgimento do linfoma MALT. Este estudo foi realizado através de um levantamento bibliográfico nas bases de dados: Biblioteca Virtual em Saúde (BVS), Scientific Eletronic Library Online (SciELO), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) na PubMed (National Library of Medicine), com auxílio dos Descritores de Ciências da Saúde (DeCS): Helicobacter pylori, Linfoma MALT e Câncer Gástrico, agrupados com o operador booleano “AND” e “OR”. Os critérios de inclusão foram artigos gratuitos, em português e ingles, com recorte temporal de 2011 a 2022. Os critérios de exclusão foram estudos que fora do tema proposto, repetidos, incompletos, resumos simples ou resenhas. A coleta resultou em 112 artigos, 47 eram duplicados e outros 65 foram excluídos pela leitura rápida de título e resumo, restando 30 estudos lidos por completo e após analise mais 18 foram eliminados, restando 12 artigos para compor essas pesquisa. Como resultado e conclusão das pesquisas, identificou-se que a H. pylori causa modificações químicas e celulares, principalmente inflamatórias, resultando em desequilíbrio e envelhecimento celular, tornando-a um fator predisponente ao linfoma MALT.

Epoxy-carvone (EC) has chiral centers that allow generation of stereoisomers, including (+)-cis-EC and (-)-cis-EC, whose effects in the kindling tests have never been studied. Accordingly, this study aims to comparatively investigate the effect of stereoisomers (+)-cis-epoxy-carvone and (-)-cis-epoxy-carvone on behavioral changes measured in scores, in the levels of cytokines (IL-1β, IL-6, and TNFα) and neuronal protection in the face of continuous treatment with pentylenetetrazol. Swiss mice were divided into five groups (n = 10), receiving vehicle, (+) - cis-EC, (-) - cis-EC (both at the dose of 30 mg/kg), and diazepam (4 mg/kg). Thirty minutes after the respective treatment was administered to the animals one subconvulsive dose of PTZ (35 mg/kg). Seven subconvulsives treatments were made on alternate days, in which each treatment several parameters were recorded. In the eighth treatment, the animals receiving the highest dose of PTZ (75 mg/kg) and were sacrificed for quantification of cytokines and histopathologic analysis. All drugs were administered by intraperitoneal route. In the kindling test, (+)-cis-EC and (-)-cis-EC reduced the average scores. The stereoisomer (+)-cis-EC decreased levels of proinflammatory cytokines IL-1β, IL-6, and TNFα, whereas comparatively (-)-cis-EC did not reduce IL-1β levels. Histopathological analysis of the mice hippocampi undergoing this methodology showed neural protection for treated with (+)-cis-EC. The results suggest that the anticonvulsant effect of (+)-cis-EC possibly takes place due to reduction of proinflammatory cytokines involved in the epileptogenic process, besides neuronal protection, yet further investigation of the mechanisms involved is required.

Cancer is one of the most urgent problems in medicine. In recent years, cancer is the second leading cause of death globally. In search for more effective and less toxic treatment against cancer, natural products are used as prototypes in the synthesis of new anticancer drugs. The aim of this study was to investigate the in vivo toxicity and the mechanism of antitumor action of 7-isopentenyloxycoumarin (UMB-07), a coumarin derivative with antitumor activity. The toxicity was evaluated in vitro (hemolysis assay), and in vivo (micronucleus and acute toxicity assays). Ehrlich ascites carcinoma model was used to evaluate in vivo antitumor activity of UMB-07 (12.5, 25, or 50 mg/kg, intraperitoneally, i.p.), after 9 days of treatment, as well as toxicity. UMB-07 (2000 μg/mL) induced only 0.8% of hemolysis in peripheral blood erythrocytes of mice. On acute toxicity assay, LD50 (50% lethal dose) was estimated at around 1000 mg/kg (i.p.), and no micronucleated erythrocytes were recorded after UMB-07 (300 mg/kg, i.p.) treatment. UMB-07 (25 and 50 mg/kg) reduced tumor volume and total viable cancer cells. In the mechanism action investigation, no changes were observed on the cell cycle analysis; however, UMB-07 reduced peritumoral microvessels density and CCL2 chemokine levels. In addition, UMB-07 showed weak toxicity on biochemical, hematological, and histological parameters after 9 days of antitumor treatment. The current findings suggest that UMB-07 has low toxicity and exerts antitumor effect by inhibit angiogenesis via CCL2 chemokine decrease.

As Leishmanioses constituem um problema que afeta principalmente as pessoas mais pobres e com maior dificuldade de acesso aos serviços de saúde. No Brasil, a Leishmania chagasi é o principal agente etiológico. Objetivou-se analisar a incidência da LV em municípios da Nona Gerência Regional de Saúde do estado da Paraíba. O Estudo transversal retrospectivo, compreendido no período de 2010 a 2014, obtidos no Sistema de Informação de Agravos de Notificação (SINAN). Os dados foram analisados quanto ao número de casos, coinfecção com HIV, confirmação clínica, epidemiológica e laboratorial, escolaridade, óbito, cor/raça, faixa etária e sexo. Foram registrados 34 casos de LV, dos quais a maior incidência foi observada nos anos de 2011 (11) e 2014 (12). A cidade Cajazeiras foi a cidade mais afetada (16 casos), seguida pela cidade de Triunfo (6 casos). Quanto a escolaridade, 9 dos casos registrados eram indivíduos que não concluíram o ensino fundamental. A faixa etária mais relevante foi de 20 a 34 anos (8 casos), seguida por pessoas de 1 a 4 anos (7 casos). 25 dos casos notificados eram do sexo masculino (74%) e 9 são do sexo feminino (26%). A alta incidência de LV foi observada em algumas cidades da 9ª regional de saúde, este fato, está diretamente associada a deficiência nas medidas de controle dos vetores e a falta da efetivação de medidas que visem a conscientização da população. Com este trabalho podemos perceber que é necessário adotar medidas para controle desta zoonose, estas precisam ser colocadas em prática urgentemente. Epidemiological analysis of visceral leishmaniasis in the Hinterland Paraibano MunicipalitiesAbstract: The Leishmaniasis constitute a problem it mainly affects the poorest and more difficult access to health services people. In Brazil, Leishmania chagasi is the main etiological. The objective analyze incidence of VL in municipalities of the Ninth Regional Health Management of Paraiba. A retrospective cross-sectional study comprised the period from 2010 to 2014, Obtained in the SINAN (Sistema de Informação de Agravos de Notificação). Data were analyzed for the number of cases, coinfection with HIV, clinical, epidemiological and laboratory confirmation, education, death, color/race, age and sex. 34 cases of VL were recorded, maximum number of cases were reported in 2011 (11) and 2014 (12). Cajazeiras city was the most affected (16 cases), followed by the Triunfo (6 cases). When we analyze the school level, 9 cases was reported in people did not complete primary school. The most relevant age group was 20-34 years (8 cases), followed by 1-4 years group (7 cases). Twenty-five of the reported cases were male (74%) and nine are female (26%). The high incidence of VL was observed in some regional health 9th cities, this fact is directly linked to deficiency in vector control measures and the lack of effective measures aimed at public awareness. With this work we can see the need to adopt measures to control this zoonosis, these need to be put into practice urgently.

Hydantoins are often reported as potent anticonvulsant drugs; however, recent studies have highlighted their antinociceptive potential. Based on these reports, this study investigated the antinociceptive and anti-inflammatory activities of the hydantoin derivative 5-(4-isopropylphenyl)-3-phenyl-imidazolidine-2,4-dione (IM-7) using animal models. Treated mice submitted to the acetic acid-induced writhing test showed increase (p

Structural diversity characterizes natural products as prototypes for design of lead compounds. The aim of this study was to synthetize, and to evaluate the toxicity and antitumor action of a new piperine analogue, the butyl 4-(4-nitrobenzoate)-piperinoate (DE-07). Toxicity was evaluated against zebrafish, and in mice (acute and micronucleus assays). To evaluate the DE-07 antitumor activity Ehrlich ascites carcinoma model was used in mice. Angiogenesis, Reactive Oxygen Species (ROS) production and cytokines levels were investigated. Ninety-six hours exposure to DE-07 did not cause morphological or developmental changes in zebrafish embryos and larvae, with estimated LC50 (lethal concentration 50%) higher than 100 μg/mL. On the acute toxicity assay in mice, LD50 (lethal dose 50%) was estimated at around 1000 mg/kg, intraperitoneally (i.p.). DE-07 (300 mg/kg, i.p.) did not induce increase in the number of micronucleated erythrocytes in mice, suggesting no genotoxicity. On Ehrlich tumor model, DE-07 (12.5, 25 or 50 mg/kg, i.p.) induced a significant decrease on cell viability. In addition, there was an increase on ROS production and a decrease in peritumoral microvessels density. Moreover, DE-07 induced an increase of cytokines levels involved in oxidative stress and antiangiogenic effect (IL-1β, TNF-α and IL-4). No significant clinical toxicological effects were recorded in Ehrlich tumor transplanted animals. These data provide evidence that DE-07 presents low toxicity, and antitumor effect via oxidative and antiangiogenic actions by inducing modulation of inflammatory response in the tumor microenvironment.

Natural products have an important role as prototypes in the synthesis of new anticancer drugs. Piperine is an alkaloid amide with antitumor activity and significant toxicity. Then, the N-(p-nitrophenyl)acetamide piperinoate (HE-02) was synthesized, and tested for toxicological and antitumor effects. The toxicity was evaluated in vitro (on RAW 264.7 cells and mice erythrocytes) and in vivo (acute toxicity in mice). The Ehrlich ascites carcinoma model was used to evaluate the antitumor activity of HE-02 (6.25, 12.5 or 25 mg/kg, intraperitoneally, i.p.), as well as toxicity. HE-02 induced only 5.01% of hemolysis, and reduced the viability of RAW 264.7 cells by 49.75% at 1000 &micro, g/mL. LD50 (lethal dose 50%) was estimated at around 2000 mg/kg (i.p.). HE-02 reduced Ehrlich tumor cell viability and peritumoral microvessels density. There was an increase of Th1 helper T lymphocytes cytokine profile levels (IL-1&beta, TNF-&alpha, IL-12) and a decrease of Th2 cytokine profile (IL-4, IL-10). Moreover, an increase was observed on reactive oxygen species and nitric oxide production. Weak in vivo toxicological effects were recorded. Our data provide evidence that the piperine analogue HE-02 present low toxicity, and its antitumor effect involves modulation of immune system to a cytotoxic Th1 profile.

MHTP [2-methoxy-4-(7-methoxy-1,2,3,4-tetrahydroisoquinolin-1-yl) phenol], a synthetic isoquinolinic alkaloid, presented anti-inflammatory activity in several experimental models of acute inflammation as lipopolysaccharide (LPS)-induced acute lung injury and phlogistic agent-induced edema and presented low preclinical toxicity. The aim of this study was to determine the MHTP effect on ovalbumin (OVA)-induced pulmonary allergic inflammation. In other to realize this study, female BALFB/c mice were sensitized and challenged with OVA (OVA group) and treated with MHTP (MHTP group) by nasal instillation. Inflammatory, allergic, and immunomodulatory parameters such as migration of inflammatory cells to the lung tissue, pulmonary histological analysis, serum level of IgE-allergen specific, cytokine secretion, and lung T cell population characterization were analyzed and the data were considered statistically significant with p

Curine is a bisbenzylisoquinoline alkaloid that is isolated from Chondrodendron platyphyllum, a plant that is used to treat malaria, inflammation, and pain. Recent reports have demonstrated the antiallergic effects of curine at nontoxic doses. However, its anti-inflammatory and analgesic properties remain to be elucidated. This study investigated the anti-inflammatory and analgesic effects of curine in mice. We analyzed the effects of an oral treatment with curine in the formation of paw edema, vascular permeability, abdominal contortion, licking behavior, and hyperalgesia using different inflammatory stimuli. Curine significantly inhibited the formation of paw edema by decreasing vascular permeability, inhibited the acetic acid-induced writhing response, inhibited the licking behavior during inflammation but not during the neurogenic phase of the formalin test, and inhibited carrageenan-induced hyperalgesia. Finally, curine inhibited prostaglandin E2 production in vitro without affecting cyclooxygenase-2 expression. The effects of curine treatment were similar to the effects of indomethacin, but were different from the effects of morphine treatment, suggesting that the analgesic effects of curine do not result from the direct inhibition of neuronal activation but instead depend on anti-inflammatory mechanisms that, at least in part, result from the inhibition of prostaglandin E2 production. In conclusion, curine presents anti-inflammatory and analgesic effects at nontoxic doses and has the potential for use in anti-inflammatory drug development.

Ethnopharmacological relevance Curine is a bisbenzylisoquinoline alkaloid and the major constituent isolated from Chondrodendron platyphyllum , a plant that is used to treat inflammatory diseases in Brazilian folk medicine. This study investigates the effectiveness of curine on mast cell-dependent responses in mice. Materials and methods To induce mast cell-dependent responses, Swiss mice were subcutaneously sensitized with ovalbumin (OVA—12 μg/mouse) and Al(OH) 3 in a 0.9% NaCl solution. Fifteen days later, the animals were challenged with OVA through different pathways. Alternatively, the animals were injected with compound 48/80 or histamine, and several parameters, including anaphylaxis, itching, edema and inflammatory mediator production, were analyzed. Promethazine, cromoglycate, and verapamil were used as control drugs, and all of the treatments were performed 1 h before the challenges. Results Curine pre-treatment significantly inhibited the scratching behavior and the paw edema induced by either compound 48/80 or OVA, and this protective effect was comparable in magnitude with those associated with treatment with either cromoglycate or verapamil. In contrast, curine was a weak inhibitor of histamine-induced paw edema, which was completely inhibited by promethazine. Curine and verapamil significantly inhibited pleural protein extravasations and prostaglandin D 2 (PGD 2 ) and cysteinyl leukotrienes (CysLTs) production following allergen-induced pleurisy. Furthermore, like verapamil, curine inhibited the anaphylactic shock caused by either compound 48/80 or an allergen. In in vitro settings, these treatments also inhibited degranulation as well as PGD 2 and CysLT production through IgE-dependent activation of the mast cell lineage RBL-2H3. Conclusion Curine significantly inhibited immediate allergic reactions through mechanisms more related to mast cell stabilization and activation inhibition than interference with the pro-inflammatory effects of mast cell products. These findings are in line with the hypothesis that the alkaloid curine may be beneficial for the treatment of allergic disorders.

Curine is a bisbenzylisoquinoline alkaloid (BBA) with anti-allergic, analgesic, and anti-inflammatory properties. Previous studies have demonstrated that this alkaloid is orally active at non-toxic doses. However, the mechanisms underlying its anti-inflammatory effects remain to be elucidated. This work aimed to investigate the effects of curine on macrophage activation and neutrophil recruitment. Using a murine model of lipopolysaccharide (LPS)-induced pleurisy, we demonstrated that curine significantly inhibited the recruitment of neutrophils in association with the inhibition of cytokines tumor necrosis factor (TNF-&alpha, ), interleukin (IL)-1&beta, IL-6, monocyte chemotactic protein (CCL2/MCP-1) as well as leukotriene B4 in the pleural lavage of mice. Curine treatment reduced cytokine levels and the expression of iNOS in in vitro cultures of macrophages stimulated with LPS. Treatment with a calcium channel blocker resulted in comparable inhibition of TNF-&alpha, and IL-1&beta, production, as well as iNOS expression by macrophages, suggesting that the anti-inflammatory effects of curine may be related to the inhibition of calcium-dependent mechanisms involved in macrophage activation. In conclusion, curine presented anti-inflammatory effects that are associated with inhibition of macrophage activation and neutrophil recruitment by inhibiting the production of inflammatory cytokines, LTB4 and nitric oxide (NO), and possibly by negatively modulating Ca2+ influx.

Food allergy is a severe human disease with imminent risk of life. Cissampelos sympodialis (Menispermaceae) is a native Brazilian plant used in Brazilian folk medicine for the treatment of respiratory allergies. In this study the experimental model of food allergy induced by ovalbumin (OVA) was used to determine whether the alcoholic extract of the plant (AFL) and its alkaloids match a therapeutic approach for this disease. Animal weight, diarrhea, OVA-specific IgE levels, inflammatory cell and cytokine profiles, mucus production and proportion of T cells on the mesenteric lymph node (MLN) were evaluated. Warifteine (W) or methyl-warifteine (MW) alkaloids slightly improve diarrhea score independently of AFL and all treatments decreased the OVA-specific IgE levels. Stimulated mesenteric lymph node (MLN) cells in the presence of the alkaloids diminished the IL-12p70 levels independently of IFN-γ or IL-13 secretion. The alkaloids increased the number of Treg cells on MLN and reduced the number of eosinophils and mast cells as well as mucus production in the gut. Therefore, the alkaloids modulate the immune response in food allergy by increasing regulatory T cells in MLN independently of Th1 or Th2 profiles.

In the article, “Cissampelos sympodialis has anti-viral effect inhibiting dengue non-structural viral protein-1 and pro-inflammatory mediators” [Rev. Bras. Farmacogn. 26 (2016) 502–506], the third author name “Luciana Gomez Fialho” has been corrected as “Luciana Gomes Fialho”. The online version has already been corrected.

Dengue is the most important viral infection transmitted among humans by arthropod-borne. There are currently no vaccines or specific therapeutical treatment. Therefore, immunomodulatory compounds from plants have been widely examined for their antiviral effects. Cissampelos sympodialis Eichler, Menispermaceae, has scientifically proven to present immunomodulatory activities. Here we assessed the antiviral activity of leaf hydroalcoholic extract, warifteine or methylwarifteine from C. sympodialis in an in vitro dengue virus infection model. The results demonstrated that leaf hydroalcoholic extract or warifteine/methylwarifteine treatment did not reduce dengue virus-Ag+ hepatocyte (Huh-7 cell) rates in present experimental conditions. However, we assessed the potential antiviral effect of leaf hydroalcoholic extract or warifteine/methylwarifteine on dengue virus-infection by the production of inflammatory molecules, TNF-α, MIF, IL-8 and PGE2. Dengue virus infection enhanced TNF-α, MIF, IL-8 and PGE2 production in infected Huh-7 cells and leaf hydroalcoholic extract but not warifteine/methylwarifteine treatments, significantly reduced these molecules in infected cells. In dengue virus-infected Huh-7 cells, non-structural protein-1 is produced and leaf hydroalcoholic extract significantly inhibited it independently of alkaloids. Our findings imply that leaf hydroalcoholic extract may attenuate dengue virus infection in Huh-7 cells by inhibiting the enhanced of pro-inflammatory mediators and non-structural protein-1 production induce by dengue virus independently of warifteine/methywarifteine its major compound. Keywords: Cissampelos sympodialis, Dengue, Huh-7 cells, Cytokines, NS1, Warifteine

Bornyl salicylate (BS) is a salicylic derivative, obtained by sterification of salicylic acid and monoterpene (-)-borneol, and its topical use in inflammatory diseases was described in the early 20th century. It is also known that borneol presents neuroprotective, genoprotective and analgesic properties. The purpose of this study was to evaluate BS in experimental models of acute inflammation. The toxicity of BS was analyzed by measuring water and food intake, weight, mortality and weight of main organs. To assess its anti-inflammatory effect, BS-treated mice were challenged with carrageenan, prostaglandin E2 (PGE2), bradikynin (BK) or histamine (HIS)-induced paw edema, zymosan-induced peritonitis and vascular permeability induced by acetic acid. Nitric oxide (NO) production was analyzed in peritoneal macrophage cultures. There was no sign of acute toxicity of BS in male and female mice. Furthermore, treatment with BS was significantly (p < 0.05) effective in reducing paw edema induced by carrageenan in early and late phases; this effect was related to PGE2 and BK, but HIS independent. Neutrophil migration and cytokine release (TNF-α, IL-1β and IL-6) induced by zymosan and fluid leakage induced by acetic acid were also reduced in BS-treated animals. In vitro, BS (10 µg/mL) reduced NO production in LPS-stimulated macrophages. These data suggest that BS has an anti-inflammatory effect, which is related, at least in part, with decrease of mediators as PGE2, NO and pro-inflammatory cytokines. However, further studies should be done to explore its potential as an anti-inflammatory drug.

Ortho-eugenol is a much used phenylpropanoid whose ability to reduce pain and inflammation has never been studied. Researching ortho-eugenol's antinociceptive and anti-inflammatory activity, and its possible mechanisms of action is therefore of interest. The administration of vehicle, ortho-eugenol (50, 75 and 100mg/kg i.p.), morphine (6mg/kg, i.p.) or dexamethasone (2mg/kg, s.c.) occurred 30min before the completion of pharmacological tests. Pretreatment with ortho-eugenol did not change motor coordination test results, but reduced the number of writhes and licking times in the writhing test and glutamate test, respectively. The reaction time from thermal stimulus was significantly increased in the hot plate test after administration of ortho-eugenol. Treatment with yohimbine reversed the antinociceptive effect of ortho-eugenol, suggesting involvement of the adrenergic system. In anti-inflammatory tests, ortho-eugenol inhibited acetic acid induced vascular permeability and leukocyte migration, reducing TNF-α and IL-1β by virtue of its suppression of NF-κB and p38 phosphorylated forms in the peritonitis test. From these results, ortho-eugenol antinociceptive effects mediated by the adrenergic system and anti-inflammatory activity through regulation of proinflammatory cytokines and phosphorylation of NF-kB and p38 become evident for the first time.

Nerolidol, an acyclic sesquiterpene found as a major constituent of several essential oils, has several pharmacological activities, but its action in pain processes has never been studied. The purpose of our research was to evaluate the antinociceptive and anti-inflammatory activities of nerolidol, as well as possible mechanisms of action, in experimental mouse models of pain. Antinociceptive activity was evaluated using the acetic acid-induced writhing test, the formalin test, and the hot-plate test. The nerolidol-treated group showed lesser acetic acid-induced abdominal contractions than the control group in all of the three doses tested (200, 300, and 400 mg/kg, p.o.). The formalin test doses of 300 and 400 mg/kg p.o. inhibited licking time, in both the first phase and the second phase. In the hot-plate test, nerolidol did not alter latency at any of the observed time points. Motor coordination, evaluated through the rotarod test, was not hindered in animals treated with nerolidol. Regarding the mechanism of action, the antinociceptive activity of nerolidol is related to the GABAergic system, and not to the opioidergic or ATP-sensitive K(+) channels. Treatment with nerolidol reduced carrageenan-induced paw edema. In the model of carrageenan-induced peritonitis, nerolidol decreased the influx of polymorphonuclear cells and also reduced levels of tumor necrosis factor (TNF-α) in peritoneal lavage. Nerolidol reduced production of interleukin 1 beta (IL-1β) in LPS-stimulated, peritoneal macrophages. Thus, these results showed that nerolidol has antinociceptive activity with possible involvement of the GABAergic system, and anti-inflammatory activity, attributed to the suppression of TNF-α and IL-1β proinflammatory cytokines.