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1.
Chem Biodivers ; 21(2): e202301279, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38190837

RESUMO

For years, crop protection from pest attack, has been dominated by the use of synthetic insecticides. However, many of them can cause severe environmental problems and human health. In this context, the use of plant extracts constitutes an alternative to avoid this kind of contaminants. In this work, we investigated the chemical constituents and insecticidal activity of different extracts of leaves and stems of Argemone ochroleuca Sweet (Papaveraceae) against three economically important pests Sitophilos zeamais (Coleoptera:Curculionidae), Galleria mellonella (Lepidoptera:Pyralidae) and Xyleborus ferrugineus (Coleoptera:Scolytidae). A GC-MS analysis mostly revealed the presence benzylisoquinoline alkaloids such as allocryptopine, protopine, among others. For the insecticidal activity, after nine hours of contact, the methanolic leaves extract showed a 100 % of mortality, followed by the dichloromethane stems extract with up to 93 % of mortality. The results suggest that the benzylisoquinoline alkaloids are involved in the insecticidal activity through the octopaminergic system of the tested insects.


Assuntos
Alcaloides , Argemone , Benzilisoquinolinas , Inseticidas , Mariposas , Papaveraceae , Gorgulhos , Animais , Humanos , Inseticidas/farmacologia , Extratos Vegetais/farmacologia
2.
J Appl Res Intellect Disabil ; 37(5): e13276, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39010739

RESUMO

BACKGROUND: The present study examines the relationship between stereotypical beliefs about people with intellectual disabilities, desire for social distance, and general knowledge about human sexuality with attitudes towards the sexuality of adults with mild intellectual disabilities. METHOD: Two hundred fifty participants from staff, family and community samples completed an online set of questionnaires. RESULTS: Higher agreement with stereotypical beliefs and lower sexual knowledge were associated with less normalising and more paternalistic attitudes towards the sexuality of adults with mild intellectual disabilities. Higher agreement with stereotypical beliefs was also associated with more negative attitudes. On the other hand, willingness to interact with these adults was associated with more normalising and less paternalistic attitudes. CONCLUSIONS: Interventions that aim to support adults with intellectual disabilities in relation to their sexuality should also address the perceptions of their support network towards them as individuals with disabilities, as well as their knowledge about sexuality.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Deficiência Intelectual , Distância Psicológica , Sexualidade , Estereotipagem , Humanos , Masculino , Deficiência Intelectual/psicologia , Feminino , Adulto , Pessoa de Meia-Idade , Sexualidade/psicologia , Adulto Jovem , Idoso , Adolescente
3.
J Intellect Disabil ; : 17446295241276028, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39158225

RESUMO

Background: The sexual expression of adults with intellectual disabilities can be hindered by negative attitudes towards their sexuality. This study aims to examine current attitudes of staff, family, community and students towards the sexuality of adults with intellectual disabilities and how sociodemographic variables may influence these attitudes. Methods: 305 participants completed an online questionnaire, including the ASEXID scale. Results: Scores were highest for the normalising attitude and lowest for the negative attitude, with intermediate scores for the paternalistic attitude. Staff and university students exhibited a more normalising attitude than families and community. Community participants exhibited a more negative attitude than staff and students. Older age was associated with less normalising and more paternalistic attitudes. Being male with a more negative attitude. Discussion: These findings should be taken into account by professionals. Intermediate scores on the paternalistic attitude may mediate difficulties in supporting adults with intellectual disabilities in their sexuality.

4.
Bioorg Med Chem Lett ; 86: 129241, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-36933671

RESUMO

Metformin is the most widely known anti-hyperglycemic, officially acquired by the USA government in 1995 and in 2001 it became the most prescribed treatment for type II diabetes. But how did it become the must-use drug for this disease in such a short period of time? it all started with traditional medicine, by using a plant known as "goat's rue" for the reduction of blood glucose levels. Its use arose in 1918 and evolved to the metformin synthesis in laboratories a couple of years later, using very rudimentary methods which involved melting and strong heating. Thus, a first synthetic route that allowed the preparation of the initial metformin derivates was established. Some of these resulted toxics, and others outperformed the metformin, reducing the blood glucose levels in such efficient way. Nevertheless, the risk and documented cases of lactic acidosis increased with metformin derivatives like buformin and phenformin. Recently, metformin has been widely studied, and it has been associated and tested in the treatment of type II diabetes, cancer, polycystic ovarian syndrome, cell differentiation to oligodendrocytes, reduction of oxidative stress in cells, weight reduction, as anti-inflammatory and even in the recent COVID-19 disease. Herein we briefly review and analyze the history, synthesis, and biological applications of metformin and its derivates.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Metformina , Humanos , Metformina/farmacologia , Metformina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Glicemia
5.
Arch Sex Behav ; 52(4): 1785-1798, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36469146

RESUMO

Consensual non-monogamy (CNM) is a non-normative relationship that can generally be defined as relationships in which the involved individuals have openly agreed that they can have other sexual and/or affective partners. Despite growing interest in CNM, little research has been conducted regarding characteristics of the involved individuals, as well as comparing CNM individuals and monogamous individuals' characteristics. Expanding this research is important, as CNM constitutes a sizeable minority group, and CNM individuals and relationships are subject to stigma and dehumanization. The present study compared CNM and monogamous individuals in terms of personality (including "dark" personality) and mating orientations (sociosexuality and long-term mating) in young Spanish university students. Main results indicated that CNM individuals did not differ much in personality nor were they prone to higher "dark" personality traits when compared to monogamous individuals. Regarding mating orientations, CNM individuals were prone to higher sociosexuality levels and lower levels of long-term mating. Interestingly, results showed positive correlations between sociosexuality and "dark" personality in monogamous individuals, but not in CNM individuals. In conclusion, young Spanish university CNM individuals seem to be more pro-sex than monogamous people and less committed to the romantic love narrative of long-term mating, but these individuals were not more untrustworthy, self-centered, ruthless, or malevolent. Results were also discussed regarding their implications in the stigma and dehumanization of CNM people.


Assuntos
Comportamento Sexual , Parceiros Sexuais , Humanos , Parceiros Sexuais/psicologia , Universidades , Comportamento Sexual/psicologia , Personalidade , Estudantes
6.
Molecules ; 28(8)2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37110691

RESUMO

Neophytadiene (NPT) is a diterpene found in the methanolic extracts of Crataeva nurvala and Blumea lacera, plants reported with anxiolytic-like activity, sedative properties, and antidepressant-like actions; however, the contribution of neophytadiene to these effects is unknown. This study determined the neuropharmacological (anxiolytic-like, antidepressant-like, anticonvulsant, and sedative) effects of neophytadiene (0.1-10 mg/kg p.o.) and determined the mechanisms of action involved in the neuropharmacological actions using inhibitors such as flumazenil and analyzing the possible interaction of neophytadiene with GABA receptors using a molecular docking study. The behavioral tests were evaluated using the light-dark box, elevated plus-maze, open field, hole-board, convulsion, tail suspension, pentobarbital-induced sleeping, and rotarod. The results showed that neophytadiene exhibited anxiolytic-like activity only to the high dose (10 mg/kg) in the elevated plus-maze and hole-board tests, and anticonvulsant actions in the 4-aminopyridine and pentylenetetrazole-induced seizures test. The anxiolytic-like and anticonvulsant effects of neophytadiene were abolished with the pre-treatment with 2 mg/kg flumazenil. In addition, neophytadiene showed low antidepressant effects (about 3-fold lower) compared to fluoxetine. On other hand, neophytadiene had no sedative or locomotor effects. In conclusion, neophytadiene exerts anxiolytic-like and anticonvulsant activities with the probable participation of the GABAergic system.


Assuntos
Ansiolíticos , Animais , Ansiolíticos/uso terapêutico , Anticonvulsivantes/uso terapêutico , Flumazenil/farmacologia , Simulação de Acoplamento Molecular , Hipnóticos e Sedativos/farmacologia , Hipnóticos e Sedativos/uso terapêutico , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Comportamento Animal
7.
Entropy (Basel) ; 25(8)2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37628207

RESUMO

In the field of image processing, noise represents an unwanted component that can occur during signal acquisition, transmission, and storage. In this paper, we introduce an efficient method that incorporates redescending M-estimators within the framework of Wiener estimation. The proposed approach effectively suppresses impulsive, additive, and multiplicative noise across varied densities. Our proposed filter operates on both grayscale and color images; it uses local information obtained from the Wiener filter and robust outlier rejection based on Insha and Hampel's tripartite redescending influence functions. The effectiveness of the proposed method is verified through qualitative and quantitative results, using metrics such as PSNR, MAE, and SSIM.

8.
Br J Clin Pharmacol ; 88(6): 2591-2604, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35083768

RESUMO

AIMS: The aim of this study was to evaluate the analgesic effectiveness and adverse reactions of ketorolac in comparison with other drugs when administered postoperatively after third molar surgery. METHODS: PubMed and Google Scholar were utilized to search for articles comparing the efficacy and safety of ketorolac and other analgesic agents after third molar surgery. Data from papers with a lower risk of bias were recorded. The overall evaluation of analgesia onset, general and subgroup evaluation of the number of patients requiring rescue analgesic medication, general and subgroup assessment of the study medication (satisfaction on the study drugs), and the overall estimation of adverse effects were performed using the Review Manager Software 5.3 to analyse the data and obtain the meta-analysis plot. RESULTS: The subgroup evaluation of the study medication showed that patients who received ketorolac 30 mg were more satisfied than those who were given parecoxib 1 mg (odds ratio [OR] = 8.57, 95% confidence interval [CI] = 3.66-20.08, P = .00001), parecoxib 2 mg (OR = 7.17, 95% CI = 2.88-17.86, P = .0001), parecoxib 5 mg (OR = 3.03, 95% CI = 1.69-5.41, P = .0002), and parecoxib 10 mg (OR = 2.42, 95% CI = 1.36-4.32, P = .003). Moreover, patients who received ketorolac reported fewer adverse reactions compared with those who had received opioid analgesics (OR = 0.14, 95% CI = 0.32-1.76, P = .0001). CONCLUSIONS: The data from this study demonstrates that the postoperative administration of ketorolac 30 mg presents better results on patient satisfaction when compared to parecoxib 1 mg to 10 mg, and presents a similar satisfaction to parecoxib 20 mg following third molar removal.


Assuntos
Cetorolaco , Dente Serotino , Analgésicos/efeitos adversos , Analgésicos Opioides/efeitos adversos , Anti-Inflamatórios não Esteroides , Método Duplo-Cego , Humanos , Cetorolaco/efeitos adversos , Dente Serotino/cirurgia , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Preparações Farmacêuticas , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Bioorg Med Chem Lett ; 63: 128649, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35245665

RESUMO

Zygomycetes are ubiquitous saprophytes in natural environments which transform organic matter. Some zygomycetes of gender Mucor have attracted interest in health sector. Due to its ability as opportunistic microorganisms infecting immuno-compromised people and to the few available pharmacological treatments, the mucormycosis is receiving worldwide attention. Concerning to the pharmacological treatments, some triazole-based compounds such as fluconazole are extensively used. Nevertheless, we focused in the quinolines since they are broadly used models for the design and development of new synthetic antifungal agents. In this study, the fungistatic activity on M. circinelloides of various 2-aryl-4-aryloxyquinoline-based compounds was discovered, and in some cases, it resulted better than reference compound fluconazole. These quinoline derivatives were synthesized via the Csp2-O bond formation using diaryliodonium(III) salts chemistry. A QSAR study was carried out to quantitatively correlate the chemical structure of the tested compounds with their biological activity. Also, a docking study to identify a plausible action target of our more active quinolines was carried out. The results highlighted an increased activity with the fluorine- and nitro-containing derivatives. In light of the few mucormycosis pharmacological treatments, herein we present some non-described molecules with excellent in vitro activities and potential use in the mucormycosis treatment.


Assuntos
Mucormicose , Quinolinas , Fluconazol , Humanos , Mucor , Mucormicose/tratamento farmacológico , Mucormicose/microbiologia , Relação Quantitativa Estrutura-Atividade , Quinolinas/farmacologia , Quinolinas/uso terapêutico
10.
Org Biomol Chem ; 20(25): 5009-5034, 2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-35703407

RESUMO

Iodine(III) reagents have attracted chemical relvance in organic synthesis by their use as safe, non-toxic, green and easy to handle reagents in different transformations. These characteristics make them important alternatives to procedures involving hazardous and harsh reaction conditions. Their versatility as oxidants has been exploited in the functionalization of different aromatic cores, which allow the introduction of several groups. Metal-free arylation using iodine(III) reagents is by far one of the most described topics in the literature; however, other highly relevant non-aromatic groups have been also introduced. Herein, we summarize the most representative developed procedures for the functionalization of aryls and heteroaryls by introducing halogens, using different iodine(III) reagents.


Assuntos
Iodo , Halogenação , Indicadores e Reagentes , Iodetos , Oxirredução , Estresse Oxidativo
11.
Molecules ; 27(9)2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35565963

RESUMO

Tagetes parryi is a plant empirically used to treat gastrointestinal and inflammatory diseases, its essential oil (EOTP) was obtained from the aerial parts, and the composition was elucidated by GC-MS. The in vivo and in vitro anti-inflammatory activities and the antinociceptive activity of EOTP and (1S)-(-)-verbenone (VERB) were assessed. The major compounds identified for EOTP were verbenone (33.39%), dihydrotagetone (26.88%), and tagetone (20.8%). EOTP and VERB diminished the ear oedema induced with TPA by 93.77 % and 81.13 %, respectively. EOTP and VERB decreased inflammation in a 12-O-tetradecanoylphorbol-13-acetate (TPA) chronic model with ED50 = 54.95 mg/kg and 45.24 mg/kg, respectively. EOTP (15 µg/mL) inhibited the in vitro production of the pro-inflammatory mediators NO (67.02%), TNF-α (69.21%), and IL-6 (58.44%) in LPS-stimulated macrophages. In the acetic induced writhing test, EOTP and VERB showed antinociceptive effects with ED50 = 84.93 mg/kg and ED50 = 45.24 mg/kg, respectively. In phase 1 of the formalin test, EOTP and VERB showed no antinociceptive effects, whereas in phase 2, EOTP (ED50 = 35.45 mg/kg) and VERB (ED50 = 24.84 mg/kg) showed antinociceptive effects. The antinociceptive actions of ETOP and VERB were blocked with the co-administration of L-NAME. This study suggests that EOTP and VERB might be used in the treatment of pain and inflammatory problems.


Assuntos
Asteraceae , Óleos Voláteis , Tagetes , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Monoterpenos Bicíclicos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Extratos Vegetais/farmacologia
12.
Bioorg Med Chem Lett ; 50: 128329, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34418572

RESUMO

The sphingomyelin pathway is important in cell regulation and determining cellular fate. Inhibition of sphingosine kinase isoform 1 (SK1) within this pathway, leads to a buildup of sphingosine and ceramide, two molecules directly linked to cell apoptosis, while decreasing the intracellular concentration of sphingosine-1-phosphate (S1P), a molecule linked to cellular proliferation. Recently, an inhibitor capable of inhibiting SK1 in vitro was identified, but also shown to be ineffective in vivo. A set of compounds designed to assess the impact of synthetic modifications to the hydroxynaphthalene ring region of the template inhibitor with SK1 to obtain a compound with increased efficacy in vivo. Of these fifteen compounds, 4A was shown to have an IC50 = 6.55 µM with improved solubility and in vivo potential.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Desenho de Fármacos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Humanos , Concentração Inibidora 50 , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , Conformação Proteica , Relação Estrutura-Atividade
13.
Clin Oral Investig ; 25(12): 6779-6790, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33907893

RESUMO

OBJECTIVES: The aim of this meta-analysis was to assess the clinical efficacy and safety profile of ropivacaine in comparison with other dental anesthetics in different clinical conditions. MATERIALS AND METHODS: This meta-analysis was registered in the National Institute for Health Research PROSPERO (ID: CRD42020205580). PubMed and Scholar Google were consulted to identify clinical trials using ropivacaine in comparison with other local anesthetic drugs for any dental procedure. Articles comparing ropivacaine and other dental anesthetics were assessed with the Cochrane Collaboration's risk of bias tool. Data from reports without a high risk of bias were extracted (anesthetic and adverse effects) and analyzed using the Review Manager Software 5.3. for Windows and the Risk Reduction Calculator. RESULTS: Ropivacaine produces a longer anesthetic time when compared with lidocaine/adrenaline (n = 260; p = 0.00001) and similar anesthesia than bupivacaine (n = 190). CONCLUSIONS: Data of this study indicate that ropivacaine infiltration produces a longer anesthetic time when compared with lidocaine and articaine but not when compared to bupivacaine in dental procedures. CLINICAL RELEVANCE: Ropivacaine was more effective than lidocaine for dental anesthesia. For this reason, the manufacture of a ropivacaine dental cartridge with a suitable concentration could be an important advancement for clinical practice.


Assuntos
Anestesia Dentária , Anestésicos Locais , Bupivacaína , Carticaína , Lidocaína , Ropivacaina
14.
Inflammopharmacology ; 29(1): 295-306, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32333259

RESUMO

Cuphea aequipetala Cav (Lythraceae) is an herb used in folk treatment for pain and inflammation. The aim of this study was to evaluate the antinociceptive and anti-inflammatory actions of an ethanol extract from the leaves and stem of Cuphea aequipetala (CAE). The antinociceptive actions of CAE (10-200 mg/kg p.o.) were assessed with the acetic acid-induced writhing, hot plate, and formalin tests. The possible mechanism of action of CAE was evaluated using inhibitors. The effects of CAE on motor coordination were assessed by the rotarod test. The in vitro anti-inflammatory actions of CAE were evaluated using LPS-stimulated primary murine macrophages, and the in vivo anti-inflammatory actions were assessed by the TPA-induced ear oedema and the carrageenan-induced paw oedema tests. The production of inflammatory mediators was estimated from both in vitro and in vivo assays. CAE showed antinociception (ED50 = 90 mg/kg) in the acetic acid test and in the second phase of the formalin test (ED50 = 158 mg/kg). Pretreatment with glibenclamide or L-NAME partially reversed the antinociception shown by the plant extract. CAE (50-200 mg/kg) did not affect motor coordination in mice. CAE increased the production of IL-10 in LPS-stimulated macrophages (EC50 = 10 pg/ml) and, in the carrageenan-induced paw oedema test (threefold increase). In conclusion, CAE induced antinociceptive effects without affecting motor coordination, probably due to the involvement of nitric oxide and ATP-sensitive K+ channels. CAE also exerts in vitro and in vivo anti-inflammatory effects by increasing the release of IL-10.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Cuphea/química , Extratos Vegetais/farmacologia , Analgésicos/administração & dosagem , Analgésicos/isolamento & purificação , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edema/tratamento farmacológico , Edema/patologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Canais KATP/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Dor/tratamento farmacológico , Extratos Vegetais/administração & dosagem
15.
Saudi Pharm J ; 29(9): 1056-1060, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34305423

RESUMO

BACKGROUND: The aim of this study was to assess the frequency of allopathic and complementary medicine use for preventing the infection with SARS-CoV-2 in Mexico. A descriptive and cross-sectional study was conducted using an online questionnaire among general adult population (n = 16,724) of the 32 Mexican states from March to November 2020. METHODS: The factors associated with the use, self-medication practice, and adverse reactions due the consumption of allopathic and complementary medicine to prevent infection with SARS-CoV-2 virus were assessed using a structured questionnaire. The suspected adverse reactions associated with the use of drugs or complementary medicine were reported. RESULTS: The prevalence (42.9%) of allopathic and/or complementary medicine use for preventing SARS-CoV-2 infection was mainly associated with unemployment [OR:2.026 (1.722-2.283)]. Acetaminophen (n = 2272) and vitamin C (n = 3252) were the main allopathic and complementary medicine products used to prevent SARS-CoV-2 infection, respectively. The prevalence of self-medication and adverse reactions was 35.3% and 4.8%, respectively. Self-medication [OR:1.930 (1.633-2.282)] and adverse reactions [OR:2.603 (2.015-3.363)] were mainly associated with individuals of low socioeconomic status. Hydroxychloroquine (21.2%) and chloroquine (15.2%) showed the highest prevalence of adverse reactions, which were mainly related to gastrointestinal disorders. CONCLUSION: The use of medications and complementary medicine to prevent SARS-CoV-2 infection is prevalent (almost one-half of the respondents) among Mexican population, and it is mainly associated with unemployment. Self-medication and the adverse reactions derived from self-medication are also prevalent and seem to be influenced by low socioeconomic status.

16.
Bioorg Med Chem Lett ; 30(9): 127063, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32139323

RESUMO

The first study about the anxiolytic activity of two chiral tetrahydrocarbazoles is presented. This new chiral compounds were prepared through an organocatalytic strategy via trienamine activation. The in situ ortho-quinodimethane species, formed by the condensation of the N-protected 2-methylindole acrylaldehyde with a sterically hindred diarylsilylprolinol ether derivative as catalyst, easily participate in a Diels-Alder reaction with the ethyl cyanophenyl acrylate as dienophile, in good yields and excellent stereoselectivity. These compounds showed activity against anxiety and mood disorders that can possibly contribute in the discovery of new drugs. In addition, the use of N-protected 2-methylindole acrylaldehyde will set a new base for the synthesis of medically and pharmacologically important tetrahydrocarbazoles via trienamine catalysis.


Assuntos
Ansiolíticos/síntese química , Ansiolíticos/farmacologia , Carbazóis/síntese química , Carbazóis/farmacologia , Animais , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Relação Estrutura-Atividade
17.
Drug Dev Res ; 81(5): 600-608, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32181517

RESUMO

This work describes the neuropharmacological (sedative, anxiolytic, antidepressant, and anticonvulsant) actions of Gardenin A (GA) (0.1-25 mg/kg p.o.), a flavonoid found in medicinal plants. The sedative effects of GA were assessed with the pentobarbital-induced sleep test. The anxiolytic actions of GA were evaluated with the elevated plus-maze, the light-dark box test, the exploratory cylinder assay, and the open field test. Motor coordination was evaluated with the rotarod test and the open field test. The antidepressant-like actions of GA were evaluated with the tail suspension test and forced swimming test. The mechanisms of the anxiolytic-like and antidepressant-like effects of GA were assessed using inhibitors of neurotransmission pathways. The anticonvulsant activity of GA was evaluated with the strychnine-induced seizure test. The sedative effects of GA were evident only at a dose of 25 mg/kg, which increased the duration of sleep but did not alter sleep onset. GA showed anxiolytic-like actions with activity comparable to that of clonazepam in all experimental tests. The GABAA receptor antagonist bicuculline reversed the anxiolytic-like effects of GA. Furthermore, GA showed significant antidepressant-like actions in both models with activity comparable to that of fluoxetine. Yohimbine, an α2-adrenoceptor blocker, inhibited the antidepressant-like actions of GA. In addition, GA (1-10 mg/kg) did not affect locomotor coordination in mice and delayed the onset of convulsions. These findings suggest that GA induces anxiolytic-like effects and has anticonvulsant actions by the possible involvement of the GABAergic system. The antidepressant-like actions of GA may be mediated by noradrenergic neurotransmission.


Assuntos
Ansiolíticos/uso terapêutico , Anticonvulsivantes/uso terapêutico , Antidepressivos/uso terapêutico , Flavonas/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Convulsões/tratamento farmacológico , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Exploratório/efeitos dos fármacos , Masculino , Camundongos Endogâmicos BALB C , Teste de Desempenho do Rota-Rod , Convulsões/induzido quimicamente , Estricnina , Natação
18.
Inflammopharmacology ; 28(3): 749-757, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31754938

RESUMO

INTRODUCTION: Bidens odorata Cav (Asteraceae) is a medicinal plant employed for the treatment of pain, anxiety, and depression. This study aimed to evaluate some neuropharmacological effects of an ethanol extract of B. odorata (BOE) and assess its antinociceptive interaction with naproxen and paracetamol. MATERIALS AND METHODS: The following neuropharmacological effects were evaluated with the ethanolic extract of B. odorata leaves (BOE) (10-200 mg/kg p.o.): the strychnine-induced-convulsion assay (anticonvulsant effect), rotarod test (locomotor activity), tail suspension test (anti-depressant-like activity), cylinder exploratory test (anxiolytic-like actions), and pentobarbital-induced sleep test (sedative effect). The interaction of the BOE-paracetamol and BOE-naproxen combinations were evaluated with the acetic acid-induced writhing test. The ED50 value of each drug was estimated and the combinations of paracetamol and naproxen with BOE were calculated. RESULTS: BOE (100-200 mg/kg) showed anti-convulsant activity by increasing the latency to occurrence of strychnine-induced convulsions, antidepressant-like effects by 28% and 33%, respectively, exerted anxiolytic actions (ED50 = 125 mg/kg), but did not affect motor locomotion. The pre-treatment with 2 mg/kg flumazenil or 20 mg/kg pentylenetetrazol partially reverted the anxiolytic activity shown by BOE alone. BOE (200 mg/kg) prolonged the duration of sleep with similar effect in comparison to clonazepam (1.5 mg/kg). The combinations of BOE-paracetamol (1:1) and BOE-naproxen (1:1) showed antinociceptive synergism. CONCLUSION: BOE induces sedative and anticonvulsant effects. The anxiolytic actions shown by BOE are probably induced by the participation of the GABAergic system. BOE exerts antinociceptive synergistic interaction with paracetamol and naproxen probably by the participation of nitric oxide and ATP-sensitive K+ channels, respectively.


Assuntos
Acetaminofen/farmacologia , Anticonvulsivantes/farmacologia , Asteraceae/química , Bidens/química , Sistema Nervoso Central/efeitos dos fármacos , Naproxeno/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Analgésicos/farmacologia , Animais , Ansiolíticos/farmacologia , Antidepressivos/farmacologia , Interações Medicamentosas/fisiologia , Etanol/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Dor/tratamento farmacológico , Extratos Vegetais/química , Convulsões/tratamento farmacológico
19.
Inflammopharmacology ; 28(2): 541-549, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31679123

RESUMO

Senna septemtrionalis (Viv.) H.S. Irwin & Barneby (Fabaceae) is a medicinal plant used as a folk remedy for inflammation and pain. The objective of this study was to evaluate the anti-inflammatory and antinociceptive actions of an ethanol extract of Senna septemtrionalis aerial parts (SSE). The in vitro anti-inflammatory effects of SSE were assessed using LPS-stimulated macrophages and the subsequent quantification of the levels of cytokines (IL-6, IL-1ß, and TNF-α) with ELISA kits, nitric oxide (NO), and hydrogen peroxide (H2O2). The in vivo anti-inflammatory actions of SSE were evaluated with the TPA-induced ear oedema test and the carrageenan-induced paw oedema test. The antinociceptive actions of SSE (10-200 mg/kg p.o.) were assessed using three models: two chemical assays (formalin-induced orofacial pain and acetic acid-induced visceral pain) and one thermal assay (hot plate). SSE showed in vitro anti-inflammatory actions with IC50 values calculated as follows: 163.3 µg/ml (IL-6), 154.7 µg/ml (H2O2) and > 200 µg/ml (IL-1ß, TNF-α, and NO). SSE showed also in vivo anti-inflammatory actions in the TPA test (40% of inhibition of ear oedema) and the carrageenan test (ED50 = 137.8 mg/kg p.o.). SSE induced antinociceptive activity in the formalin orofacial pain test (ED50 = 80.1 mg/kg) and the acetic acid-induced writhing test (ED50 = 110 mg/kg). SSE showed no antinociceptive actions in the hot plate assay. The pre-treatment with glibenclamide abolished the antinociceptive action shown by SSE alone. Overall, SSE exerted in vitro and in vivo anti-inflammatory actions, and in vivo antinociceptive effects by the possible involvement of ATP-sensitive K + channels.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Extratos Vegetais/farmacologia , Senna/química , Analgésicos/administração & dosagem , Analgésicos/isolamento & purificação , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edema/tratamento farmacológico , Edema/patologia , Etanol/química , Peróxido de Hidrogênio/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Concentração Inibidora 50 , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Camundongos Endogâmicos BALB C , Dor/tratamento farmacológico , Extratos Vegetais/administração & dosagem
20.
Molecules ; 25(24)2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33339310

RESUMO

Many studies describe different pharmacological effects of flavonoids on experimental animals and humans. Nevertheless, few ones are confirming the safety of these compounds for therapeutic purposes. This study aimed to investigate the preclinical safety of naringenin, naringin, hesperidin, and quercetin by in vivo, in vitro, and in silico approaches. For this, an MTT-based cytotoxicity assay in VERO and MDCK cell lines was performed. In addition, acute toxicity was evaluated on Wistar rats by OECD Guidelines for the Testing of Chemicals (Test No. 423: Acute Oral Toxicity-Class Method). Furthermore, we used the ACD/Tox Suite to predict toxicological parameters such as hERG channel blockade, CYP450 inhibition, and acute toxicity in animals. The results showed that quercetin was slightly more cytotoxic on cell lines (IC50 of 219.44 ± 7.22 mM and 465.41 ± 7.44 mM, respectively) than the other citroflavonoids. All flavonoids exhibited an LD50 value > 2000 mg/kg, which classifies them as low-risk substances as OECD guidelines established. Similarly, predicted LD50 was LD50 > 300 to 2000 mg/kg for all flavonoids as acute toxicity assay estimated. Data suggests that all these flavonoids did not show significant toxicological effects, and they were classified as low-risk, useful substances for drug development.


Assuntos
Peso Corporal/efeitos dos fármacos , Flavonoides/farmacologia , Administração Oral , Animais , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/metabolismo , Cães , Canal de Potássio ERG1/antagonistas & inibidores , Canal de Potássio ERG1/metabolismo , Feminino , Flavanonas/química , Flavanonas/metabolismo , Flavanonas/farmacologia , Flavonoides/química , Flavonoides/metabolismo , Dose Letal Mediana , Células Madin Darby de Rim Canino , Medicina Tradicional , Quercetina/química , Quercetina/metabolismo , Quercetina/farmacologia , Ratos , Ratos Wistar , Células Vero
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