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.

No abstract

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 µg/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-1β, TNF-α, 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.

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 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.

No abstract

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.

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.