Intranasal in situ gelling liquid crystal for delivery of resveratrol ameliorates memory and neuroinflammation in Alzheimer's disease.

Alzheimer's disease (AD) is an illness that affects people aged 65 or older and affects around 6.5 million in the United States. Resveratrol is a chemical obtained from natural products and it exhibits biological activity based on inhibiting the formation, depolymerization of the amyloid, and decreasing neuroinflammation. Due to the insolubility of this compound; its incorporation in surfactant-based systems was proposed to design an intranasal formulation. A range of systems has been produced by mixing oleic acid, CETETH-20 and water. Polarised light microscopy (PLM), small angle x-ray scattering (SAXS) and transmission electron microscopy (TEM) confirm the initial liquid formulation (F) presented as microemulsion (ME). After dilution, the gelled systems were characterized as hexagonal mesophase and they showed feasibility proprieties. Pharmacological assays performed after intranasal administration showed the ability to improve learning and memory in animals, as well as remission of neuroinflammation via inhibition of interleukin.

DYRK1A Inhibitors and Perspectives for the Treatment of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is a chronic neurodegenerative disease and the most common form of dementia, especially in the elderly. Due to the increase in life expectancy, in recent years, there has been an excessive growth in the number of people affected by this disease, causing serious problems for health systems. In recent years, research has been intensified to find new therapeutic approaches that prevent the progression of the disease. In this sense, recent studies indicate that the dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) gene, which is located on chromosome 21q22.2 and overexpressed in Down syndrome (DS), may play a significant role in developmental brain disorders and early onset neurodegeneration, neuronal loss and dementia in DS and AD. Inhibiting DYRK1A may serve to stop the phenotypic effects of its overexpression and, therefore, is a potential treatment strategy for the prevention of ageassociated neurodegeneration, including Alzheimer-type pathology. OBJECTIVE: In this review, we investigate the contribution of DYRK1A inhibitors as potential anti-AD agents. METHODS: A search in the literature to compile an in vitro dataset including IC50 values involving DYRK1A was performed from 2014 to the present day. In addition, we carried out structure-activity relationship studies based on in vitro and in silico data. RESULTS: molecular modeling and enzyme kinetics studies indicate that DYRK1A may contribute to AD pathology through its proteolytic process, reducing its kinase specificity. CONCLUSION: further evaluation of DYRK1A inhibitors may contribute to new therapeutic approaches for AD.

Geraniol accelerates the gastric healing, minimizes ulcers recurrence, and reduces anxiolytic-like behavior in ulcerated rodents by oral or inhaled route.

BACKGROUND: Geraniol (GE) is dietary acyclic monoterpene alcohol found in essential oils from aromatic plants with therapeutic value against gastric ulcers already described. HYPOTHESIS/PURPOSE: To assess whether oral GE accelerates gastric healing or prevents ulcer recurrence, and to evaluate the hypothesis that GE promotes antiulcer effects by the inhaled route and that promotes changes in the behavior of ulcerated rodents. METHODS: Gastric healing effects, underlining mechanisms, and behavioral changes were measured in80% acetic acid-induced gastric ulcer model in rats receiving GE by oral (30 mg/kg) or inhaled route (1 mg/L of air/min); whereas the effects of GE to avoid ulcer recurrence was evaluated in mice submitted to 10% acetic acid plus IL-1ß ulcer. RESULTS: GE administered by both routes accelerates gastric healing, increasing mucin and GSH levels, CAT, and GST activities, and reducing MPO activity. Moreover, oral, and inhaled GE minimized ulcer recurrence reducing gastric TNF and IL-6 levels and preserving mucin levels. Interestingly, the inhalation or oral intake of GE promotes anxiolytic-like effects in ulcerated rats. CONCLUSION: Data altogether suggest that the GE accelerates gastric healing through the strengthening of protective factors of the gastric mucosa, promoting a quality healing that reduces the recurrence of the lesion. Besides, the anxiolytic-like effect of GE may also contribute to its gastric healing action since anxiety is recognized as one of the etiologic agents of ulcers.

Baccharis dracunculifolia DC Hydroalcoholic Extract Improves Intestinal and Hippocampal Inflammation and Decreases Behavioral Changes of Colitis Mice.

The hydroalcoholic extract of B. dracunculifolia (HEBD) and its major compound p-coumaric acid were evaluated against the severity of intestinal inflammation and behavioral changes like depressive and anxious behavior in colitis mice. Colitis was induced in Swiss mice by oral dextran sulfate sodium (DSS) administration for five days. The mice received vehicle (10 ml/kg), HEBD (3, 30, or 300 mg/kg), or p-coumaric acid (15 mg/kg) orally, once a day for twelve days. Behavioral tests were performed on the 11th and 12th days after the beginning of the treatments. Moreover, the colon, cortex, and hippocampus were collected to analyze oxidative and inflammatory parameters. The treatment with HEBD (300 mg/Kg), but not p-coumaric acid, showed decreased disease activity index (DAI) values compared to the vehicle group and partially preserved the villi architecture and mucin levels. Furthermore, the HEBD increased the antioxidant defenses in the colon and hippocampus and reduced the myeloperoxidase activity and IL-6 levels in the colon from colitis mice. Colitis mice treated with HEBD did not show depressive-like behavior in the tail suspension test. HEBD reduced colon inflammation, while it maintains antioxidant defenses and mucin levels in this tissue. It may reduce neuropsychiatric comorbidities associated with colitis through its antioxidant effects.

Phytochemical Analysis and Antinociceptive Properties of Hydroalcoholic Extracts of Aleurites moluccanus Bark.

Aleurites moluccanus is used in folk medicine to treat many diseases including pain and inflammatory processes in general. Considering the potential of the leaf extract, evidenced in a previous study, the present study investigates the antinociceptive and anti-inflammatory properties of the hydroethanolic extract of A. moluccanus bark and isolated compounds in animal models of pain. The antinociceptive and anti-inflammatory activities of A. moluccanus bark were evaluated through hyperalgesia induced by carrageenan, PGE2, cytokines, bradykinin, epinephrine, Freund's complete adjuvant, and lipopolysaccharide. Five compounds were isolated from the dichloromethane bark extract: acetyl aleuritolic acid, atraric acid, spruceanol, (5ß,10α)-12-hydroxy-13-methoxy-8,11,13-podocarpatrien-3-one and sonderianol. To optimize the extraction conditions, ethanol 50, 70, and 90°GL were used as extracting solvent, in a 1 : 20 (w/v) drug : solvent ratio, under stirring at room temperature for 4 h. The extracts were named AMC50, AMC70, and AMC90, respectively. These extracts were administered to mice (250 mg/kg, p. o.) with reduced mechanical hyperalgesia activity in the carrageenan test. Of these, AMC90 showed the best results. Pure (5ß,10α)-12-hydroxy-13-methoxy-8,11,13-podocarpatrien-3-one showed a beneficial effect for up to 48 hours after the administration of carrageenan, while acetyl aleuritolic acid was effective only in the first hour. AMC90 was able to reverse the analgesia induced only by prostaglandin E2 and tumor necrosis factor. We also induced hyperalgesia using the lipopolysaccharide and Freund's complete adjuvant models, with positive results. These results support the antinociceptive and anti-inflammatory activity of A. moluccanus bark extract. The observed effects are partly due to the presence of acetyl aleuritolic acid, atraric acid, and (5ß,10α)-12-hydroxy-13-methoxy-8,11,13-podocarpatrien-3-one.

Plumieride exerts anxiolytic-like effect mediated by GABAergic and monoaminergic systems.

Plumieride (PLU), an iridoid isolated from Allamanda cathartica flowers, has been studied by our research group due to its anti-inflammatory potential, antidepressant-like and anxiolytic-like effects. This research investigated the involvement of GABAergic and monoaminergic systems in the anxiolytic-like effect elicited by PLU. Therefore, mice were pre-treated with GABAergic, serotonergic, adrenergic or dopaminergic receptor antagonists (i.p.), and exposed to Elevated Plus-Maze (EPM) and Open-Field Test (OFT). The preliminary results revealed that PLU (p.o.) possibly interacts with the mentioned systems through the GABAA, GABAB, 5-HT1A, 5-HT3, α1, α2, and D2 receptors.

Effects of 2',6'-dihydroxy-4'-methoxydihidrochalcone on innate inflammatory response.

Chalcones present potential therapeutic activities reported on literature, which led us to evaluate the anti-inflammatory effects and the acute toxicity of 2',6'-dihydroxy-4'-methoxydihydrochalcone (DHMDC) using in vitro and in vivo models. The anti-inflammatory activity was firstly in vitro investigated using macrophages (RAW 264.7) and neutrophils previously treated with DHMCD activated with lipopolysaccharide (LPS). Nitrite, IL-1ß, and TNF levels were measured in the macrophage culture supernatant, and the adhesion molecule expression (CD62L, CD49D, and CD18) was evaluated in neutrophils. Then, carrageenan-induced inflammation was performed in the subcutaneous tissue of male Swiss mice. Leukocyte migration and histological analysis were performed in the pouches. Toxicological studies were carried out on female Swiss mice (600 mg/kg) through biochemical parameters and histopathological analysis. In vitro, the DHMCD significantly reduced the IL-1ß, TNF, and nitrite levels. The DHMCD was also able to modulate the percentage of positive neutrophils for CD62L, without modifying the expression of CD18 or CD49d. In vivo, DHMCD (3 mg/kg, p.o.) significantly reduced neutrophil migration to inflammatory exudate and subcutaneous tissue. No evidence of toxic effect was observed considering the biochemical parameters and histopathological analysis of liver and kidney. Together, the obtained data shows that DHMCD presents anti-inflammatory activity by modulating the macrophage inflammatory protein secretion and also by blocking the CD62L cleavage in neutrophils. Furthermore, there was not any evidence of toxic effect in acute toxicological analysis.

Antidepressant-like effect of hydroalcoholic extract from barks of Rapanea ferruginea: Role of monoaminergic system and effect of its isolated compounds myrsinoic acid A and B.

Major Depressive Disorder (MDD) is a highly disabling condition and has been linked to increased inflammatory mediators. Hydroalcoholic extract from barks of Rapanea ferruginea (HEBRF) and the majoritary compounds-myrsinoic acid A (MAA) and B (MAB)-have been studied due to their anti-inflammatory potential, but there is no evidence about its antidepressant-like effects. This research investigated the HEBRF, MAA, and MAB antidepressant-like effect, besides the involvement of the monoaminergic system and MAO-A activity in the HEBRF antidepressant-like effect. HEBRF (50-300 mg/kg, p.o.), MAA (5-30 mg/kg, p.o.) or MAB (3-60 mg/kg, p.o.) were administrated to mice, and behavioral parameters were assessed using the tail suspension test (TST), splash test (ST) and open field test (OFT). The involvement of monoaminergic system in the HEBRF antidepressant-like effect was established through the pretreatment of mice with antagonists. The influence triggered by HEBRF in the monoamine oxidase A (MAO-A) activity was evaluated in the hippocampus (HIP) and prefrontal cortex (PFC) of mice. HEBRF (100-300 mg/kg) promoted antidepressant-like effect in the TST and augmented the total time of grooming in the ST, without compromising the locomotor activity. Pretreatment of mice with serotoninergic, dopaminergic, and noradrenergic antagonists, reversed the HEBRF antidepressant-like effect. Besides, HEBRF inhibited the MAO-A activity in the HIP and PFC. Moreover, MAA (5 mg/kg) and MAB (3 mg/kg) also promoted antidepressant-like and anti-anhedonic effects in mice. Data showed that monoaminergic system is involved in the HEBRF antidepressant-like effect, besides MAA and MAB possibly could be responsible for these pharmacological effects.

Structure-activity relationships of sulfonamides derived from carvacrol and their potential for the treatment of Alzheimer's disease.

Five synthetic sulfonamides derived from carvacrol, a natural product and a small molecule with druglike properties, were evaluated with respect to their effects on the cognitive deficits of animals with streptozotocin (STZ)-induced Alzheimer's disease (AD). Memory, ambulation, anxiety and oxidative stress were evaluated. In vitro assays were performed to assess the inhibition of acetylcholinesterase (AChE), and the data were combined with molecular docking for the establishment of structure-activity relationships. The memories of animals treated with the compounds derived from morpholine (1), hydrazine (3) and 2-phenol (5) were improved. Compound 3 was the most promising, yielding excellent results in the inhibitory avoidance test. Moreover, the compounds did not exhibit any deleterious effects on the animals' ambulation in the open field test. Molecular docking confirmed the results obtained in the AChE inhibition assay. In short, compounds 1, 3 and 5 can reduce STZ-induced deficits and show potential for the treatment of Alzheimer's. In addition, these agents produce significant anxiolytic and antioxidant effects.

Iniquidades de género e vulnerabilidade às ist/hiv/aids em adolescentes de assentamento urbano: um estudo exploratório / Gender inequalities and vulnerability to sti/hiv/aids in urban settlement adolescents: an exploratory study / Iniquidades de género y vulnerabilidad a las its/vih/sida en adolescentes de asentamiento urbano: un estudio exploratorio

RESUMO Objetivo: Compreender a percepção acerca da vulnerabilidade às IST/HIV/AIDS entre as adolescentes residentes em assentamento urbano de uma capital do Brasil Central. Material e Método: Estudo descritivo e exploratório, com abordagem qualitativo, realizado em assentamento da periferia de uma capital do Brasil Central. De um total de 407 adolescentes da única instituição do assentamento, 107 foram considerados para o estúdio, 20 deles assistiram à consulta hebiátrica até atingir a saturação dos dados, a amostra final foi constituída por 16 adolescentes. Os dados foram obtidos por meio de entrevistas semiestruturadas. A análise de conteúdo foi utilizada para tratar os dados, sob a ótima da Teoria das Representações Sociais. Resultados: Emergiram as seguintes categorias temáticas: sentimento de invulnerabilidade às IST/HIV/AIDS; relação de gênero e vulnerabilidade às IST/HIV/AIDS e sexualidade, rede social e vulnerabilidade às IST/HIV/AIDS. Conclusão: As adolescentes assentadas são marcadas pela subalternidade de gênero, que muitas vezes é negada e naturalizada pelos ideais de legitimação de desigualdade entre os sexos.

ABSTRACT Objective: To understand the perception about the vulnerability to STI/HIV/AIDS among female adolescents living in an urban settlement in a city of Central Brazil. Materials and Methods: Descriptive and exploratory study, with qualitative approach, carried out in an urban settlement on the outskirts of a capital city in central Brazil. From a population of 407 adolescents from the only educational institution in the settlement, 107 were considered for the study. Of these, 20 went for hebiatric consultation and, until data saturation was reached, the final sample consisted of 16 adolescents. Data were obtained through semi-structured interviews. Content analysis was used to treat the data from the perspective of the Theory of Social Representations. Results: The following thematic categories emerged: feeling of invulnerability to STI/HIV/AIDS; gender relationship and vulnerability to STI/HIV/AIDS and sexuality, social network and vulnerability to STI/HIV/AIDS. Conclusion: Adolescent girls from the settlement are marked by gender subordination, which is often denied by them and naturalized by the ideals of legitimizing gender inequality.

RESUMEN Objetivo: Comprender la percepción sobre la vulnerabilidad a las IST/VIH/SIDA entre las adolescentes que viven en un asentamiento urbano en una capital del centro de Brasil. Material y Método: Estudio descriptivo y exploratorio, de abordaje cualitativo, realizado en un asentamiento urbano de la periferia de una capital de Brasil central. De un total de 407 adolescentes de la única institución del asentamiento, 107 fueron considerados para el estudio, de ellos, 20 acudieron a consulta hebiátrica y hasta que se alcanzó la saturación de datos, la muestra final quedó constituida por 16 adolescentes. Los datos se obtuvieron a través de entrevistas semiestructuradas. El análisis de contenido se utilizó para tratar los datos, bajo el óptimo de la Teoría de las representaciones sociales. Resultados: Surgieron las siguientes categorías temáticas: sensación de invulnerabilidad a las IST/VIH/ SIDA; Relación de género y vulnerabilidad a las IST/VIH/SIDA y Sexualidad, red social y vulnerabilidad a las IST/VIH/SIDA. Conclusión: Las adolescentes asentadas están marcadas por la subordinación de género, que a menudo es negada y naturalizada por los ideales de legitimar la desigualdad entre los sexos.

Antidepressant-like effect and toxicological parameters of extract and withanolides isolated from aerial parts of Solanum capsicoides All. (Solanaceae).

The present work describes the evaluation of the antidepressant-like activity of the extract, fractions, and compounds obtained from the aerial parts of Solanum capsicoides. The methanolic extract (MESC) obtained by conventional maceration was partitioned with solvents of increasing polarities yielding the respective fractions of hexane (HE), dichloromethane (DCM), and ethyl acetate (EA). The dichloromethane and ethyl acetate fractions were submitted to chromatographic and spectroscopic techniques, leading to the isolation and identification of cilistadiol (1), astragalin (2), and cilistol A (3). In relation to the antidepressant activity, the extract was active against the forced swimming test (FST) at a concentration of 300 mg/kg an ED50 (deffective dose that reduces 50% of immobility time) of 120.3 (117.3-123.4) mg/kg. Similar values were observed when evaluated in the tail suspension test (TST). In addition, the results showed no influence on motor behavior when evaluated in the open field test (OFT). Based on the observed profile of the MESC, dichloromethane fraction presenting the best profile, in both FST and TST test. Likewise, the fraction also did not present motor impairment when evaluated by the OFT test. Considering that the dichloromethane fraction was more effective, the isolated compounds cilistadiol and cilistol A were evaluated in the same experimental models. In FST, both compounds had a significant antidepressant-like effect, with ED50 values of 0.22 (0.16-0.28) and 1.03 (0.89-1.18) µmol/kg, respectively. When evaluated in the TST, showed ED50 values of 0.30 (0.18-0.52) and 1.49 (1.27-1.73) µmol/kg, respectively. The isolated compounds also did not present significant differences in the motor behavior when evaluated on OFT test in comparison with the control group. No toxicological parameters were observed until the highest dose of MESC (2000 mg/kg), demonstrating safety in the use of this plant.

Aleurites moluccanus and its main active constituent, the flavonoid 2″-O-rhamnosylswertisin, in experimental model of rheumatoid arthritis.

ETHNOPHARMMACOLOGICAL RELEVANCE: Aleurites moluccana is used in folk medicine to treat pain, fever, asthma, hepatitis, gastric ulcer and inflammatory process in general, and the nut oil had been topically applied to treat arthritis and other joint pain, however the seeds are classified as toxic for oral use. AIM: Faced with the need for new alternative to treat the symptoms and modify rheumatoid arthritis (RA) the aim of this work was to evaluate the effects of A. moluccanus' leaves dried extract in rats and mice submitted to complete Freund adjuvant (CFA)-induced RA. MATERIAL AND METHODS: Wistar Rats and Swiss mice were submitted to CFA-induced RA in the right hindpaw. They received A. moluccanus extract (orally; p.o.), dexamethasone (subcutaneously), 2″-O-rhamnosylswertisin (p.o.) or vehicle (p.o.), from the 14th day after the CFA injection for up to 8 days. The mechanical hypersensitivity was evaluated using the von Frey filaments and the paw-oedema was measured using a plethysmometer. The rats' injected hindpaw was used to perform the histological analysis. RESULTS: A. moluccanus was able to significantly reduce the mechanical hypersensitivity in both ipsi- and contralateral hindpaws of mice injected with CFA, in a dose dependent manner. Furthermore, the paw-oedema was progressively reduced by A. moluccanus. Similar results were obtained for the positive-control drug dexamethasone and the isolated compound 2″-O-rhamnosylswertisin. Besides the effects mentioned above, the extract was also effective to repair the joint damage in CFA-induced RA rats, including reduction of fibrosis, cartilage degradation and bone erosion scores. CONCLUSION: These results together with the literature data reinforce the anti-hypersensitivity and anti-inflammatory activity of A. moluccanus extract. Part of the observed effects is due to the presence of the compound 2″-O-rhamnosylswertisin. The fact that the extract acted as a disease modifier point this herbal product as a promisor and safe tool to treat RA and other associated chronic diseases.

Epidemiology of HIV, syphilis, and hepatitis B and C among manual cane cutters in low-income regions of Brazil.

BACKGROUND: In recent decades the epidemic of asymptomatic sexually transmitted infections has extended deep into Brazil, including small towns and rural areas. The purpose of this study was to investigate the epidemiology of HIV, syphilis, and hepatitis B (HBV) and hepatitis C viruses (HCV), and to evaluate immunization coverage against hepatitis B in a group of rural workers in Brazil. METHODS: In 2016, a cross-sectional study was conducted with 937 manual sugarcane cutters of the Midwest and Northeast Regions of Brazil. All individuals were interviewed and screened for HIV, syphilis, HBV and HCV. Correlating factors with lifetime HBV infection were investigated using logistic regression. Positive Predictive Values, Negative Predictive Values, sensitivity and specificity were also calculated relative to vaccination against Hepatitis B, comparing anti-HBs titers to vaccination reports. RESULTS: Most reported previous hospitalization (55%), occupational injuries (54%), sharing of personal items (45.8%), alcohol consumption (77.2%), multiple sexual partners in previous 12 months (39.8%), and no condom use during sexual intercourse in last 12 months (46.5%). Only 0.2% reported using injection drugs. Anti-HIV-1 was detected in three individuals (0.3%). Serological markers of lifetime syphilis (treponemal test) were detected in 2.5% (95% CI: 1.6-3.6) of participants, and active syphilis (treponemal test and VDRL) present in 1.2%. No samples were positive for anti-HCV. The prevalence of lifetime HBV infection (current or past infection) was 15.9%, and 0.7% (95% CI 0.4 to 1.5) were HBsAg-positive. Previous hospitalization (OR 1.53, CI 1.05-2.24, p < 0.01) and multiple sexual partners in the last 12 months (OR 1.80, CI 1.25-2.60, p < 0.01) were predictors for lifetime HBV infection. Although 46.7% (95% CI 43.4-49.9) of individuals reported having been vaccinated against hepatitis B, only 20.6% (95% CI 18.1-23.3) showed serological evidence of previous hepatitis B vaccination (positive for anti-HBs alone). CONCLUSIONS: The high prevalence of syphilis and HBV compared to the general population and the high frequency of risk behaviors show the potential for sexual and parenteral dissemination of these agents in this rural population. In addition, the low frequency of hepatitis B vaccinated individuals suggests a need for improved vaccination services.

Association between arterial hypertension and nutritional status in adolescents from Goiânia, Goiás, Brazil.

INTRODUCTION: Adolescents are a population with unique lifestyle challenges, including physical inactivity, inadequate nutrition, and obesity, all of which increase the risk of developing hypertension (HTN). The objective of this study has been to estimate the prevalence of factors associated with hypertension in adolescents in the city of Goiânia City, Central Brazil. METHODS: Between 2013and2014, a cross-sectional population study on cardiovascular risk in adolescents, was conducted with the participation of 1,586 adolescents in 108 classes at 36 schools (public and private) in Goiânia city. All of the adolescents were interviewed to establish their sociodemographic and behavioral characteristics related to hypertension and nutritional status. Anthropometric and blood pressure data were collected following a protocol. A Poisson regression, stratified by gender, was used to verify the factors associated with HTN. RESULTS: In this mixed-gender group of 1,586 students, the prevalence of HTN was 6.2% (95% CI: 4.6-8.2%) in girls and 14.0% (95% CI: 10.2-18.8%) in boys-about twice as high in boys as in girls (p <0.001). Obesity was independently associated with HTN in both genders. Being overweight was a risk factor for HTN. In addition, there was a positive correlation between the SBP/SBP percentile and the BMI Z-score/Nutritional status (NS)in both genders. A high prevalence of physical inactivity was also observed in the adolescents investigated, especially in the girls. On the other hand, more boys than girls were found to be obese. CONCLUSION: The results of this investigation revealed the need for strategies to prevent and control HTN and its risk factors, especially in Brazil's schools. In addition to the constant surveillance of HTN prevalence and risk factors (in particular, being overweight or obese), information should be distributed to promote beneficial health behaviors among adolescents.

Neuropharmacological and acute toxicological evaluation of ethanolic extract of Allamanda cathartica L. flowers and plumieride.

Psychiatric diseases affect more than 350 million people all over the world, and medicinal plants have been considered the basis for pharmacological research. The study investigates the anticonvulsant and antidepressant-like activities and acute toxicological effects of ethanolic extract of Allamanda cathartica flowers, and plumieride. The extract was analyzed by HPLC and plumieride was isolated. Toxicity studies were carried out on females Wistar rats (2000 mg/kg). Toxicity was evaluated by measuring biochemical parameters and conducting histopathological analysis. For pharmacological evaluation different doses of the extract (100, 150 and 300 mg/kg, p.o.) and plumieride (0.5, 1 and 2 µg/kg, i.p.) were administered before the Forced-Swimming Test (FST), pentylenetetrazole seizure test (PTZT) or Tail-Suspension Test (TST) in mice. Furthermore, hemolytic activity, cytotoxicity and micronucleus test were performed. In addition, mutagenicity and reproductive/developmental toxicity were estimated by TEST-software analysis. Data show that both treatments induce significant antidepressive-like effect in FST and TST, but not anticonvulsant effect. The effect of plumieride last up to 4 h after treatment. No signs of toxicity, mutagenicity, cytotoxicity or hemolytic activity were observed. The TEST-software demonstrated that plumieride present reproductive/developmental toxicity. Together, the data obtained show that the flowers extract and plumieride present antidepressant-like effect and did not present signals of acute toxicity.

Inhibitory effect of sesquiterpene lactones and the sesquiterpene alcohol aromadendrane-4ß,10α-diol on memory impairment in a mouse model of Alzheimer.

Alzheimer's disease (AD), a progressive neurodegenerative disorder of the aged brain with no known cause or cures, has become a major medical and social problem for industrialized countries. Cerebral deposition of amyloid-ß peptide (Aß) is a critical feature of AD. The use of medicinal plants as an alternative form of prevention, or even as a possible treatment of AD, is therefore interesting areas of research. Sesquiterpene lactones and a sesquiterpene alcohol are compounds found in H. brasiliense that have several anti-oxidative and anti-inflammatory effects. In the present study, we investigated whether these compounds have neuroprotective effects in an amyloid-ß peptide-induced Alzheimer's disease mouse model. Mice were injected with Aß1-42 peptide intracerebroventricularly and were subsequently injected (i.c.v.) with 1µg/site of IGM-A (15-acetoxy-isogermafurenolide), IGM-H (15-hydroxy-isogermafurenolide), PDA (Podoandin), EHP (1,2-epoxy-10α-hydroxy-podoandin), HDS (13-hydroxy-8,9-dehydroshizukanolide), and ARD (aromadendrane-4ß,10α-diol). Seven days after treatments the animals had their memory tested in the inhibitory avoidance. After the behavioral testing of animals the brains were removed and subjected to biochemical tests for oxidative stress. The results showed that ARD, HDS and PDA significantly ameliorated the Aß1-42 peptide-induced memory impairment in the passive avoidance task (P<0.05). In addition, GSH activity was increased while the TBARS levels were decreased by treatment with these compounds. These results suggest that these compounds inhibit the cognitive deficit of animals induced peptide amyloid and may be potential candidates for Alzheimer's disease therapy.

Perceptions of adolescent students about drugs.

OBJECTIVE: To analyze the perceptions of adolescent public school students about drugs. METHOD: Qualitative approach of focus groups with 16 adolescent students. The data collected were analyzed by means of content analysis, leading to the following categories: meaning of drugs; living with drug use; opinions, beliefs and attitudes toward drug use; and preventing drug abuse in adolescence. RESULTS: The adolescent students know about some drugs, and associate their use with delinquent and criminal behavior. The students identified factors that lead to drug abuse, such as easy access, use by family and friends, idleness, dropping out of school and the characteristic vulnerability of adolescence. CONCLUSION: the results point to the need for educational activities in the context of where the adolescents live, including school, community and family environments, to support and to minimize their vulnerability.

Antidepressant-like effect of quercetin in bulbectomized mice and involvement of the antioxidant defenses, and the glutamatergic and oxidonitrergic pathways.

Olfactory bulbectomy (OB) is an animal model of depression that can mimic symptoms that are characteristic of depressive patients, such as behavioral, neurochemical and neuromorphological changes. Quercetin decreased the immobility time in the forced swimming test and tail suspension test. With the open field test, quercetin did not alter the locomotor activity of mice and in the splash test, quercetin increased the time spent grooming. The repeated treatment with quercetin (25mg/kg, for 14days) reversed the behavioral hyperactivity induced by OB in the open field test and was able to prevent depressant-like effects in the forced swimming test and tail suspension test. Regarding oxidative stress, OB reduced the levels of glutathione and increase the activity of superoxide dismutase and lipid hydroperoxide content (LOOH) in the hippocampus. Only the increase in LOOH levels was reversed by treatment with quercetin. In a further series of experiments with non-bulbectomized mice, the antidepressant effect of quercetin in the tail suspension test was reversed by the pretreatment of mice with NMDA, l-arginine or sildenafil. The administration of methylene blue and 7-nitroindazole, in combination with an underactive dose of quercetin (5mg/kg, p.o.), decreased the immobility time in the tail suspension test compared with the use of drug alone. There was no significant change in locomotor activity in the open field test. Our results suggest that the antidepressant effect of quercetin is dependent on the inhibition of the NMDA receptors and/or synthesis of nitric oxide. In addition, considering the reduction of LOOH levels on the hippocampus, we verify that the antioxidant effects of quercetin also contribute to its antidepressive potential. These data contribute to the understanding of the mechanisms involved in the antidepressant effect of quercetin and reinforce the involvement of the NMDA receptors and the nitric oxide on the pathophysiology of depression.

Topical curcumin-loaded hydrogels obtained using galactomannan from Schizolobium parahybae and xanthan.

The curcumin (CUR)-loaded binary hydrogel was formulated using xanthan and galactomannan from Schizolobium parahybae (guapuruvu). The binary hydrogels presented gel characteristics, stable pH values and mechanical stress resistance even after 45 days of heat exposure (45 °C). The CUR-loaded hydrogel content was 98.6% for XGMC (xanthan and galactomannan with CUR-microemulsion) after the stability test. The in vitro cytotoxicity analysis suggested non-cutaneous membrane irritation, and the in vitro skin permeation analysis indicated 2.15 to 2.50 µg mL(-1) CUR at the stratum corneum, epidermal and dermal levels. The XGEC (xanthan and galactomannan with CUR solubilized in ethanol) and XGMC hydrogels presented 76.8 and 63.2% inhibition of topical inflammation, respectively. Chemical stability and non-cytotoxicity analysis confirm the safety of prolonged exposure of the skin during the topical treatment, offering long-lasting XGEC and XGMC action.

Contribution of α,ß-Amyrenone to the Anti-Inflammatory and Antihypersensitivity Effects of Aleurites moluccana (L.) Willd.

The aim of the study was to analyze the constituents of the dichloromethane fraction obtained from A. moluccana and also to evaluate the anti-inflammatory and antinociceptive properties of α,ß-amyrenone isolated from A. moluccana in mice. The dichloromethane fraction was evaluated by gas chromatography and submitted to purification. The mixture of α,ß-amyrenone was isolated and then evaluated using the carrageenan-induced paw-oedema or pleurisy and CFA-induced arthritis models in mice. Five triterpenes, α,ß-amyrenone, glutinol, and α,ß-amyrin were isolated from dichloromethane fraction of A. moluccana leaf extract. The mixture of α,ß-amyrenone, dosed orally, was able to reduce mechanical hypersensitivity and paw-oedema induced by carrageenan, interfering with neutrophil migration. Similar results were observed in the carrageenan-induced pleurisy model. Repeated administration of the compounds was also effective in reducing the mechanical sensitization and oedema developed in the arthritis model induced by CFA. In conclusion, the results demonstrate that α,ß-amyrenone interferes in both acute and chronic inflammatory processes. We can infer that these effects involve, at least in part, a reduction in the neutrophil migration. Therefore, it seems reasonable to suggest that α,ß-amyrenone could represent a new therapeutic tool for the management of painful and inflammatory diseases, especially those presenting a chronic profile.