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A Doença de Alzheimer é uma doença neurodegenerativa progressiva que se caracteriza pela deterioração cognitiva e da memória. Este trabalho teve como objetivo avaliar, in sílico, a atividade antiacetilcolinesterase da benzofenona prenilada, composto presente na própolis vermelha, produzida por abelhas Apis mellifera. Foi realizado o docking molecular através do software HEX 8.0.0. Foi realizada uma busca dos sítios de ligações possíveis entre a benzofenona prenilada (ligante) e a enzima acetilcolinesterase (receptor). O ligante teve afinidade com o receptor, pois foram observadas 6 ligações químicas, de até 3.1 angstrons, com o recrutamento de 4 resíduos de aminoácidos (His287, Glu292, Tyr341 e Gly342) e uma glicosilação do receptor presente na estrutura tridimensional (n-acetil-glucosamina). Também se observa no sítio, a compatibilidade espacial e estabilização da enzima acetilcolinesterase a partir do encaixe do ligante e sua consequente redução da flexibilidade. Dessa forma, pode-se concluir que a benzofenona prenilada tem potencial antiacetilcolinesterase no estudo in silico, sendo capaz de agir como adjuvante, reduzindo a degradação da acetilcolina, o que pode ser um fator importante ao combate ou retardamento dos sintomas do mal de Alzheimer

Turnera subulata Sm. belongs to the family Turneraceae and is found in Brazil. The present study evaluated the antinociceptive, anti-inflammatory, and hypoglycemic potential of T. subulata flower e...

Combretaceae are reported in the literature for presenting neuroprotective and anxiolytic effects in animal models. Combretum lanceolatum Pohl. has few scientific reports on its pharmacological eff...

The species Ocimum basilicum L., Lamiaceae, is popular for culinary purposes and medicinal use as a larvicide, repellent, antifungal, and antimicrobial agent. Therefore, the aim of the present study is to evaluate the chemical composition and antinociceptive effect of the volatile oil of O. basilicum flowers using adult zebrafish (Danio rerio) (n = 6/group) treated orally (20 µl) with volatile oil (0.25, 1.25, or 2.5 mg/ml; 20 µl) or vehicle (0.9% NaCl, 20 µl). The volatile oil of the O. basilicum flowers was obtained by hydrodistillation and analyzed by GC–MS, and the antinociceptive action is evaluated by different stimuli using motor parameters. The analysis of the chemical profile identified fourteen components with linalool (1) as a major chemical constituent (56.37%). The oral administration of volatile oil did not show any acute toxicity or behavior effects in all tested doses. The volatile oil has a pharmacological potential for the treatment of acute pain by modulation of opioid system, N-methyl-d-aspartate receptors (glutamatergic receptor), and the transient receptor potential vanilloid subtype 1 and acid-sensing ion channels. Together, these data provide support for analgesic properties of the volatile oil and contribute to suggest that the adult zebrafish model presents the cheapest, cost-effective pharmacological alternative for the discovery of novel analgesics.

This work aimed to analyze the chemical composition and evaluate the anti-inflammatory and antinociceptive properties of the essential oil obtained from the leaves of Lantana montevidensis (OEFLM) in mice. The chemical composition of the OEFLM was analyzed by GC–MS, and its effects on the central nervous system were determined by the open field and rotarod tests. The antinociceptive and anti-inflammatory screenings were conducted using the formalin test, as well as the acetic acid-induced abdominal contortion assay. The antinociceptive activity was assessed by the tail-flick and hot plate tests. The systemic anti-inflammatory activity was determined using models of paw edema induced by carrageenan, dextran, histamine, or arachidonic acid. The effects of the essential oil on vascular permeability and granuloma formation were also investigated. The chemical composition of the OEFLM revealed the presence of valencene (17.93%), bicyclogermacrene (16.35%), trans-caryophyllene (12.84%) and germacrene D (12.18%). The administration of OEFLM at the dose of 2000 mg/Kg caused no evident toxicity. While OEFLM (25, 50, 100, and 200 mg/kg) did not present significant anxiolytic-loke or sedative effects, it showed promising antinociceptive and anti-inflammatory activities. The results of this study indicate that the OEFLM has analgesic and anti-inflammatory activities in animal models by inhibiting acute and chronic inflammation.

The genus Cnidoscolus (Euphorbiaceae) is widely distributed in tropical areas. In the Northeast of Brazil, the species C. quercifolius is endemic and has been used in traditional medicine. In this study, a novel protein was isolated from C. quercifolius seeds and characterized by its molecular weight, primary structure, isoelectric point (pI), and carbohydrate content. The hypoglycemic activity of this protein was investigated by in vitro assay with the RIN-5F glucose-responsive cell line and in vivo test using alloxan-induced diabetic mice models. In addition, safe use of the protein was also investigated by cytotoxicity, hemagglutinating, and immunogenicity assays. The protein which was named Cq-IMP (Cnidoscolus quercifolius - Insulin Mimetic Protein) showed a single 11.18 KDa glycopolypeptide chain (16.4% of carbohydrates, m/m), pI of 8.0 and N-terminal sequence (TKDPELKQcKKQQKKqQQYDDDDKK) with similarity around 46-62% to sucrose binding protein-like and vicilin-like protein that was confirmed by mass spectrometry tryptic peptides analysis. Besides that, Cq-IMP presented anti-insulin antibody cross-reactivity as hypoglycemic activity in both in vitro and in vivo models. Additionally, it did not present any toxicity by methods tested. In conclusion, Cq-IMP is an insulin-mimetic protein, with a potent hypoglycemic activity and no toxicity showing great potential for therapeutic applications and drug development.

The action of anxiolytic compounds that act on selective serotonin receptors (SSRIs) have been scarcely evaluated. Serotonergic drugs have been shown to be effective in treating anxiety without presenting adverse effects as benzodiazepines. However, the anxiolytic effects take days to occur. This study aimed to evaluate the anxiolytic effect of the synthetic chalcone, 4’-[(2E) -3- (3-nitrophenyl) -1- (phenyl) prop-2-en-1-one] acetamide (PAAMNBA), and its possible mechanism of action in adult zebrafish (Danio rerio). PAAMNBA was synthesized with a yield of 51.3% and its chemical structure was determined by 1H and 13C NMR. Initially, PAAPMNBA was intraperitoneally administered to zebrafish (n = 6/group) at doses of 4, 12, or 40 mg/kg, and the animals were subsequently subjected to acute and open field toxicity tests. PAAMNBA was administered to the other groups (n = 6/group) for analyzing its effect in the light and dark test. The involvement of the serotonergic (5HT) system was also evaluated using 5-HTR 1, 5-HTR 2A/2C, and 5-HTR 3A/3B receptor antagonists, namely, pizotifeo, granizetron, and ciproeptadina, respectively. Molecular coupling was performed using the 5-HT1 receptor. PAAMNBA was found to be non-toxic, reduced the locomotor activity, and had an anxiolytic effect in adult zebrafish. The effect was reduced by pretreatment with pizotifene and was not reversed by treatment with granizetron and cyproeptadine. A previous in vivo molecular coupling study indicated that chalcones interact with the 5-HT1 receptor. The results suggested that the chalcone, PAAPMNBA, has anxiolytic activity, that is mediated by the serotonergic system via the 5-HT1 receptor. The interaction of PAAPMNBA with the 5-HT1 receptor was confirmed by molecular docking studies.

Schinus terebinthifolius Raddi (Anacardiaceae) is popularly known in Brazil as aroeira-da-praia and has pharmacological use as an astringent, antidiarrheal, anti-inflammatory, depurative, diuretic,...

Aims To test for the possible antinociceptive effect of nifedipine in rodent models of acute and chronic neuropathic orofacial pain and the possible involvement of TRP- and NMDA-related processes in this effect. Methods Acute nociceptive behavior was induced by administering formalin, cinnamaldehyde, glutamate, capsaicin, or acidified saline to the upper lip or hypertonic saline to the cornea of Swiss mice. Acute nociceptive behavior was also induced by formalin injected into the TMJ or mustard oil injected into the masseter muscle of Wistar rats. The chronic pain model involved infraorbital nerve transection (IONX) in Wistar rats to induce mechanical hypersensitivity, which was assessed with von Frey hair stimulation of the upper lip. The effects of pretreatment with nifedipine or vehicle (control) were tested on the nociceptive behaviors. Docking experiments were also performed. Statistical analysis included one-way ANOVA followed by Tukey post hoc test and two-way ANOVA followed by Bonferroni post hoc test (statistical significance P Results Nifedipine produced significant antinociceptive effects in all of the acute nociceptive behaviors except that induced by capsaicin. The antinociceptive effects were attenuated by NMDA, TRPA1, or TRPM3 receptor antagonists. The IONX animals developed facial mechanical hypersensitivity, which was significantly reduced by nifedipine. The docking experiments suggested that nifedipine may interact with TRPM3 and NMDA receptors. Conclusion The present study has provided novel findings in a variety of acute and chronic orofacial pain models showing that nifedipine, a selective inhibitor of L-type Ca2+ channels, can suppress orofacial nociceptive behavior through NMDA, TRPA1, and TRPM3 receptor systems.

Este trabalho busca a avaliacao da seguranca nao clinica do triterpeno AAA frente aos ensaios com zebrafish ( Danio rerio ) adulto. O triterpeno AAA foi isolado da raiz de Croton zehntneri . Solucoes desta substância foram preparadas com salina 0,9 %, nas concentracoes de (4,0 mg/kg ou 12 mg/kg ou 40 mg/kg; 20 μL i.p) e submetidas ao teste de toxicidade aguda frente ao modelo zebrafish. As mesmas doses foram investigadas quanto ao possivel efeito ansiolitico, atraves do teste de campo aberto. As tres dosagens de AAA testadas nao foram toxicas nos zebrafish e nao reduziram a atividade locomotora do animal, tendo assim uma possivel acao nociceptiva pois a amostra nao alterou a atividade locomotora dos animais.

Comumente a industria farmaceutica utiliza metabolitos secundarios isolados de plantas como material de partida natural de novos farmacos. As plantas podem ser utilizadas como fontes terapeuticas alternativas, pois apresentam em sua composicao variedades de moleculas biologicamente ativas, como os triterpenos. Esses constituintes sao metabolitos secundarios pertencente a classe dos terpenos e sao caracterizados quimicamente pela presenca de seis unidades de isopreno, com um total de 30 atomos de carbono. Esta revisao foi realizada com base nos artigos publicados sobre triterpenos e suas bioatividades: anti-inflamatoria, antiadipogenica, antinociceptiva, antimicrobiana e anticâncer, em relacao ao periodo dos ultimos dez anos. Nesta revisao foi verificado que, as atividades relatadas comprovam que os triterpenos constituem grande potencial terapeutico.

Nanoencapsulation is a valid alternative for the oral administration of peptide drugs and proteins, as nanoparticles protect them from proteolytic degradation in the gastrointestinal tract and promote the absorption of these macromolecules. The orofacial antinociceptive effect of frutalin (FTL), through the intraperitoneal route, has already been proven. This study aimed to develop, characterize, and evaluate the orofacial antinociceptive activity of an oral formulation containing FTL in acute and neuropathic preclinical tests. Nanoencapsulated FTL was administered by oral route. The acute nociceptive behavior was induced by administering capsaicin to the upper lip and NaCl to the right cornea. The nociceptive behavior was also induced by formalin injected into the temporomandibular joint. The neuropathic pain model involved infraorbital nerve transection (IONX), which induced mechanical hypersensitivity and was assessed by von Frey stimulation. Trpv1 gene expression was analyzed in the trigeminal ganglion. The analyzed sample did not show any cytotoxicity; 52.2% of the FTL was encapsulated, and the size of the nanocapsule was less than 200 nm, the polydispersion was 0.361, and the zeta potential was - 5.87 and - 12.8 mV, with and without FTL, respectively. Nanoencapsulated FTL administered by oral route had an orofacial antinociceptive effect in acute and neuropathic rodent models. The antinociceptive effect of FTL was prevented by ruthenium red, but not by camphor. FTL reduced Trpv1 gene expression. FTL promotes orofacial antinociception, probably due to the antagonism of TRPV1 channels, and the nanoformulation represents an effective method for the oral administration of this protein. HIGHLIGHTS: • Nanoformulation for oral protein administration. • Nanocapsule containing FTL prevents orofacial nociceptive acute and neuropathic pain. • Frutalin promotes orofacial antinociception behavior antagonism of TRPV1 channels.

Myconia albicans is the most abundant genus of the melastomaceous botanical family. In Brazil, it is known as "Canela de Velho", and is used mainly in inflammatory processes. Due to the scarcity of scientific works that report its pharmacological effect, the objective of this study was to perform its chemical characterization, toxicity, and the possible effect on the nervous system, using the experimental model Zebrafish (Dario regio). The organic extract of ethyl acetate (EtOAc) was elaborated through the dry leaves of the cinnamon tree of old. The EtOAc sample was submitted to preliminary phytochemical screening and showed the presence of phenols, flavanoids of the flavones type, flavonols and xanthones, triterpenoids, and alkaloids. Then, flavonoid compounds (369.58±0.074mgEQ/g) and total phenols (81.48±0.005mgEAG/g) were determined. EtOAc was evaluated for its toxicity, with Artemia salina, which showed low toxicity in all the studied doses. In the pharmacological action tests, the doses of 3, 10, or 30 mg/mL were used; 20 µL; oral (v.o.) or intraperitoneal (i.p.). The locomotor activity was evaluated in the open field test, which showed a decrease in the fish. And the anxiolytic activity, in the light & dark preference test, showed that EtOAc at 30 mg/mL, when administered intraperitoneally (IP), has an anxiolytic effect similar to Diazepam IP control. Thus the EtOAC of M. albicans showed the presence of total phenols and several flavonoids, with low toxicity, in which the highest dose presented anxiolytic effect in Zebrafish. Myconia albicans es el género más abundante de la familia botánica de las melastomeas. En Brasil, se le conoce como "Canela de Velho" y se utiliza principalmente en procesos inflamatorios. Debido a la escasez de trabajos científicos que reporten su efecto farmacológico, el objetivo de este estudio fue realizar su caracterización química, su toxicidad y su posible efecto sobre el sistema nervioso, utilizando el modelo experimental Pez cebra (Dario regio). El extracto orgánico de acetato de etilo (EtOAc) se elaboró ​​a través de las hojas secas de la canela de antaño. La muestra de EtOAc fue sometida a un cribado fitoquímico preliminar y mostró la presencia de fenoles, flavonoides del tipo flavonas, flavonoles y xantonas, triterpenoides y alcaloides. Luego, se determinaron los compuestos flavonoides (369,58 ± 0,074 mgEQ / g) y los fenoles totales (81,48 ± 0,005 mgEAG / g). Se evaluó la toxicidad de EtOAc, con Artemia salina, que mostró baja toxicidad en todas las dosis estudiadas. En las pruebas de acción farmacológica, se utilizaron las dosis de 3, 10 o 30 mg / mL; 20 µL; oral (v.o.) o intraperitoneal (i.p.). La actividad locomotora se evaluó en la prueba de campo abierto, que mostró disminución de los peces. Y la actividad ansiolítica, en la prueba de preferencia de luz y oscuridad, mostró que EtOAc a 30 mg / mL, cuando se administra por vía intraperitoneal (IP), tiene un efecto ansiolítico similar al control de Diazepam IP. Así, la EtOAC de M. albicans mostró la presencia de fenoles totales y varios flavonoides, de baja toxicidad, en los que la dosis más alta presentó efecto ansiolítico en el pez cebra. Myconia albicans é o gênero mais abundante da família botânica melastomaceous. No Brasil, é conhecido como "Canela de Velho", e é usado, principalmente, em processos inflamatórios. Devido à escassez de trabalhos científicos que relatem seu efeito farmacológico, o objetivo deste estudo foi realizar sua caracterização química, sua toxicidade e seu possível efeito no sistema nervoso, utilizando o modelo experimental Peixe-zebra (Dario regio). O extrato orgânico de acetato de etila (EtOAc) foi elaborado por meio das folhas secas da canela de antigamente. A amostra de EtOAc foi submetida a uma triagem fitoquímica preliminar e evidenciou a presença de fenóis, flavonoides do tipo flavonas, flavonóis e xantonas, triterpenoides e alcaloides. Em seguida, os compostos flavonoides (369,58 ± 0,074mgEQ / g) e fenóis totais (81,48 ± 0,005mgEAG / g) foram determinados. O EtOAc foi avaliado quanto à sua toxicidade, juntamente com Artemia salina, que apresentou baixa toxicidade em todas as doses estudadas. Nos testes de ação farmacológica, foram utilizadas as doses de 3, 10 ou 30 mg / mL; 20 µL; oral (v.o.) ou intraperitoneal (i.p.). A atividade locomotora foi avaliada no teste de campo aberto, que mostrou diminuição dos peixes. E a atividade ansiolítica, no teste de preferência claro e escuro, mostrou que o EtOAc a 30 mg / mL, quando administrado por via intraperitoneal (IP), tem efeito ansiolítico semelhante ao controle do Diazepam IP. Assim, o EtOAC de M. albicans mostrou a presença de fenóis totais e diversos flavonoides, com baixa toxicidade, em que a maior dose apresentou efeito ansiolítico no peixe-zebra.

Os compostos com atividade antiviral eficazes para o novo coronavírus ainda são pouco conhecidos, e os terpenos são um grupo interessante de agentes naturais com atividades antivirais de longo alcance. Esta investigação visa identificar a atividade antiviral in silico do ?-bisabolol, citral, cis-jasmona e eucaliptol contra nova glicoproteína Spike do SARS-COV-2. A interação entre os terpenos e a glicoproteína Spike foi analisada in silico por meio de simulação de docking molecular, buscando formar uma complexação estável. Todas as evidências químicas, espaciais e energéticas sugerem que essas 4 substâncias são capazes de complexar e estabilizar esta proteína chave na infecção viral e sustentam a hipótese de que complexações de terpenos dificultam a entrada do vírus nas células hospedeiras.

Os estudos sobre metabolismo vêm sendo potencializados com as investigações sobre produtos naturais e suas atividades biotecnológicas. Com base nisto, o trabalho investiga a interação molecular do ácido oleanólico com o receptor TGR5 (receptor 1 de ácido biliar acoplado à proteína G), também conhecido como receptor 19 acoplado à proteína G, relatado em diversos modelos experimentais como integrante das moléculas responsáveis por regulações metabólicas capazes de exercer efeitos benéficos contra o diabetes e síndrome metabólica. O ácido oleanólico é um componente natural de muitos alimentos vegetais e ervas medicinais, já o TGR5 é um receptor proteico endógeno ligado à membrana plasmática, expresso em todo o corpo, mas apresenta níveis elevados de expressão no fígado, intestino, estômago, baço, e tecido adiposo marrom. Para promover esta interação in silico, foram obtidas as estruturas tridimensionais das duas moléculas em bancos de dados estruturais e foi realizado o docking molecular, que consiste numa complexação guiada por algoritmo e software especializado, para obtenção de complexos estruturais estáveis. Os resultados descrevem que o ácido oleanólico possui afinidade por um sítio específico do receptor TGR5, se complexando a partir de 6 ligações químicas e as atividades biotecnológicas promovidas por ele possuem alta reprodutibilidade e afinidade, o que é capaz de promover estabilização energética do receptor envolvido, no contexto metabólico, atuando como um aliado no combate à obesidade.

A diabetes é uma Doença Crônica não Transmissível (DCNT) e uma das principais causadoras da Doença Renal (DR). São muitas as restrições alimentares para os diabéticos em diálise, o que traz dificuldades aos pacientes para se adaptarem a dieta. Nesse contexto, este trabalho teve como objetivo avaliar o conhecimento sobre alimentação dos pacientes diabéticos em tratamento hemodialítico em um Centro de Nefrologia no interior do Estado do Ceará. Tratou-se de uma pesquisa descritiva, de cunho qualitativo, com pesquisa de campo aplicando-se questionário e entrevistas semiestruturadas com 10 frequentadores do referido centro, no mês de fevereiro de 2021. Os protocolos da entrevista foram submetidos na 1plataforma Brasil (#45934221.8.0000.80.74). No trabalho foi avaliado o perfil socioeconômico, tempo de tratamento hemodialítico e dificuldades sobre a alimentação para tal doença. Os dados foram analisados através do Programa Microsoft Word. Em relação ao perfil socioeconômico dos entrevistados, predomina-se pacientes que sobrevivem da agricultura e os que trabalham com comércio. Em relação ao tempo de tratamento hemodialítico, percebe-se que a maioria deles realiza o tratamento a mais de 5 anos. Os pacientes sentem dificuldades sobre a alimentação para tal doença (como por exemplo, incertezas nas escolhas dos alimentos). Pode-se concluir que os pacientes diabéticos de tal centro hemodialítico enfrentam obstáculos para manter sua alimentação de forma saudável, desde a condição financeira e oferta de alimentos, até a locomoção, pois alguns residem em zona rural e não conseguem com facilidade para a cidade.

A obesidade é uma patologia de origem multifatorial, das quais tem como principal fator contribuinte nossos hábitos alimentares, dessa forma conclui-se que o acumulo excessivo de gordura pode acarretar no surgimento de outras patologias das quais englobam as doenças crônicas não transmissíveis. Este trabalho reporta uma revisão bibliográfica de caráter qualitativo, através de materiais publicados entre os anos de 2016 e 2021 através das bases de dados eletrônicos LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde), Google Acadêmico, SCIELO e sites de órgãos públicos tais como WHO (Word Health Organization), OPAS (Organização Pan-Americana da Saúde) e OMS (Organização Mundial da Saúde). Por estar presente na maioria da população a obesidade passou a ser considerada uma doença de caráter epidêmico; e a busca por um corpo visto como padrão pela sociedade e a facilidade de propagação de medidas errôneas e equivocadas prometendo rápidos resultados aumentam a busca por dietas milagrosas por este grupo trazendo consequências metabólicas, nutricionais também psicológicas, dessa forma conclui-se que a obesidade contribui negativamente não alimentar, afetando a imagem corporal, além de favorecer o aumento das doenças crônicas não transmissíveis.

Due to the increase in fungal resistance to existing drugs, a need exists to search for new antifungals. This study aimed to evaluate the antifungal activity of α, β, and δ-damascone and inclusion complexes with β-cyclodextrin against different Candida spp. The inclusion complex of β-damascone was prepared by the co-evaporation method using three molar proportions (1:1; 2:1; 3:1 (βDA-βCD)) and analyzed using Fourier transform infrared spectroscopy (FTIR). Standard Candida albicans (CA INCQS 40,006), Candida krusei (CK INCQS 40,095), and Candida tropicalis (CT INCQS 40,042) strains were used to evaluate antifungal activity. The substances were tested individually or in association with fluconazole (FCZ). The IC

Croton heliotropiifolius Kunth (Euphorbiaceae), whose occurrence has already been registered in the most varied Brazilian biomes, is commonly found in the Chapada do Araripe, Ceará. The species is traditionally used to treat fungal, parasitic, and degenerative diseases. This study investigated the chemical composition and pharmacological potential (antioxidant, antifungal, antiparasitic, and cytotoxic) of an aqueous extract obtained from the roots of C. heliotropiifolius. Following a qualitative phytochemical screening, the chemical constituents were identified by ultra-efficiency liquid chromatography coupled witha quadrupole/time-of-flight system (UPLC-QTOF). The antioxidant potential was verified by thin-layer chromatography (TLC). The direct and combined antifungal activity of the extract against opportunistic Candida strains was investigated using the microdilution method. The minimal fungicidal concentration (MFC) was determined by subculture, while the modulation of the morphological transition (fungal virulence) was evaluated by light microscopy. The in vitro antiparasitic activity was analyzed using epimastigotes of Trypanosoma cruzi and promastigotes of Leishmania braziliensis and Leishmania infantum, while cytotoxicity was determined in cultures of mouse fibroblasts. The phytochemical analysis identified the presence of acids, terpenes, flavonoids, lignans, and alkaloids. Among these constituents, the presence of polar and non-polar phenolic compounds with known antioxidant action was highlighted. While the extract showed clinically ineffective antifungal effects, it could enhance the effectiveness of fluconazole, in addition to inhibiting the morphological transition associated with increased virulence in Candida strains. Although the extract showed low cytotoxicity against fibroblasts, it also had weak antiparasitic effects. In conclusion, Croton heliotropiifolius is a source of natural products with antifungal and antioxidant potential.

The acute effects of hyperglycemia in cognitive function and mood are not well elucidated. The aim of this study was to evaluate whether acute hyperglycemia alters the exploratory behavior of adult zebrafish. Fish were maintained aquariums containing 55 mM D-glucose solution for 14 days. Blood glucose levels and behavioral analysis were assessed before and after the D-glucose challenge. Immersion of adult zebrafish in a 55 mM D-glucose solution (14 days) increased blood glucose levels until the 14th day. There was no difference in weight gain between the two groups. Hyperglycemia did not induce anxiogenic or anxioly-tic behavior, nor did it alter the locomotor activity of the animals. We conclude that acute hyperglycemia does not alter the exploratory behavior of the adult zebrafish.

Background Vanillosmopsis arborea Baker has recognized economic value owing to the high content of (-)-α-bisabolol (BISA) in the essential oil of its stem (EOVA). The antinociceptive effect of EVOA has already been demonstrated, and β-cyclodextrin (βCD) is known to improve the analgesic effect of various substances. Purpose Thus, we aimed to evaluate the orofacial antinociceptive effect of a complex containing EOVA-βCD in rodents. Methods EOVA was obtained by simple hydrodistillation, and the essential oil was complexed with βCD. The animals (n = 6/group) were treated orally with EOVA-βCD (10 or 50 mg/kg), or vehicle (control), and subjected to cutaneous orofacial nociception (formalin, capsaicin, acidic saline or glutamate), corneal (hypertonic saline) or temporomandibular (formalin) tests. The expression of FOS protein was analyzed in the spinal cord. Molecular docking was performed using the 5-HT3 and M2 receptors and BISA. Results The oral administration of EOVA-βCD reduced nociceptive behaviour. Moreover, EOVA-βCD decreased FOS expression. The molecular docking study indicates that BISA interacts with 5-HT3 and M2 receptors, indicating the potential mechanism of action of the tested compound. Conclusions Our results indicate that EOVA-βCD possesses orofacial antinociceptive effect, indicating that this complex can be used in analgesic drug development.

This study aimed to evaluate the antinociceptive effect of oleanolic acid using adult zebrafish models of orofacial pain. Acute nociception was induced by formalin, capsaicin, cinnamaldehyde, menthol, acidified saline or glutamate (cutaneous modes) and hypertonic saline (corneal model). In another set of experiments, animals were pre-treated with naloxone, L-NAME, methylene blue, ketamine, camphor, HC-030031, mefenamic acid, ruthenium red or amiloride to investigate the mechanism of antinociception. The involvement of central afferent C-fibers was also investigated. A molecular docking was performed using the TRPV1 channel. Motor activity was evaluated with the open field test. Pre-treatment with oleanolic acid significantly reduced nociceptive behavior associated with acute pain. Antinociception was effectively inhibited by ruthenium red and capsaicin-induced desensitization. Presence of trpv1 was confirmed by RT-PCR in cerebral tissue of zebrafish. In line with in vivo experiments, docking studies indicated that oleanolic acid may interact with TRPV1. Results confirm the potential pharmacological relevance of oleanolic acid as an inhibitor of orofacial nociception mediated by TRPV1.

Zebrafish is an excellent model that can be utilized as an adjunct to current rodent models for studies of eye diseases because the anatomy and ultrastructural characterization of its cornea show much similarity with the human cornea. Therefore, we developed a behavioral model of corneal nociception using the adult zebrafish (Danio rerio). We analyzed the nociceptive effect of hypertonic saline (0.15-5.0 M sodium chloride [NaCl]) applied to the surface of the right or left cornea, on the animals' gender and locomotor activity through the open-field test. The behavioral model of corneal nociception was characterized by the antinociceptive effect of morphine (8.0 or 16 mg/kg; intraperitoneally [i.p.]), an opioid analgesic, and capsazepine, an antagonist of transient receptor potential vanilloid type 1 channels. We also tested whether the corneal antinociceptive effect of morphine could be modulated by naloxone, an opioid antagonist. Finally, we used the light and dark test to assess the anxiolytic effect of hypertonic saline (5.0 M NaCl; 5 μL) applied to the right or left cornea of the animals. As a result, hypertonic saline significantly increased (p 0.01 vs. control) the corneal nociceptive behavior of adult zebrafish (D. rerio). Morphine significantly inhibited (p 0.01 vs. 5.0 M NaCl) the hypertonic saline-induced corneal nociception and this effect was blocked by naloxone. Capsazepine (20 mg/kg; i.p.) significantly inhibited (p 0.05 vs. control) the corneal nociception induced by hypertonic saline. Hypertonic saline, applied to the surface of the right or left cornea of the animals, induced nociception and did not cause a presumptive anxiolytic effect. Gender and site of application did not affect the profile of response to hypertonic saline. The results suggest that the adult zebrafish can also be used as a behavioral model of corneal nociception, with the advantages of significant homology with the human genome and low cost.

Neem fruit (Azadirachta indica A. Juss.) are popularly used to treat infections, diarrhea, fever, bronchitis, skin diseases, infected burns and hypertension. Although the antinociceptive and anti-inflammatory potential of A. indica has already been investigated in experimental models of pain and inflammation in mice, the current research is the first to report the evaluation of the capacity of A. indica fruit ethanolic extract (EtFrNeem) in acute pain attenuation using the adult zebrafish (Danio rerio) as an alternative model to the use in rodents. EtFrNeem was submitted to antioxidant action, preliminary chemical prospecting, FT-IR and determination of phenol and flavonoid content tests. Subsequently, EtFrNeem was tested for acute nociception and abdominal inflammation, locomotor activity, and acute toxicity in adult zebrafish. Possible neuromodulation mechanisms were also evaluated. EtFrNeem showed low antioxidant activity, but was shown to be rich in flavonoids. EtFrNeem showed no anti-inflammatory action, did not alter the locomotor system, and it was not toxic. However, EtFrNeem significantly reduced the nociceptive behavior induced by formalin, glutamate and acidic saline, when compared to the control group. These effects of EtFrNeem were significantly similar to those of morphine, used as a positive control. The antinociceptive effect of EtFrNeem was inhibited by naloxone, ketamine and amiloride. EtFrNeem has the pharmacological potential for acute pain treatment and this effect is modulated by the opioid system, NMDA receptors and ASICs channels. These results lead us to studies of isolation and characterization of EtFrNeem bioactive principles, using adult zebrafish as an experimental model.

The aim of this study was to evaluate the antinociceptive effect of Kaempferol-3-O-rutinoside (KR), isolated from the plant Ouratea fieldingiana, on the orofacial nociception and possible mechanisms of action. Adult zebrafish (Danio rerio) were tested as a behavioral model to study formalin, glutamate, capsaicin, cinnamaldehyde and acidic saline-induced orofacial nociception, using as parameter the number of times the fish crossed the lines between the quadrants of a glass Petri dish during a specific time. Morphine was used as positive control. The effect of KR was tested for modulation by opioid (naloxone), nitrergic (L-NAME), TRPV1 (ruthenium red), TRPA1 (camphor) or ASIC (amiloride) antagonists. The effect of KR on zebrafish locomotor behavior was evaluated with the open field test. KR did not alter the fish's locomotor system and significantly reduced the orofacial nociceptive behavior induced by all noxious agents compared to the control group. The antinociceptive effect of KR was similar to morphine. All antagonists inhibited the antinociceptive effect of KR. KR has pharmacological potential for the treatment of acute orofacial pain and this effect is modulated by the opioid and nitrergic systems as well as TRPV1, TRPA1 and ASIC channels. These results can lead to the development of a new natural product for the treatment of orofacial pain and confirm the popular use of O. fieldingiana leaf for pain relief.

Croton blanchetianus is known as ‘marmeleiro preto’, a very widespread shrub in Northeast Brazil. Terpenoids, steroids and phenolic compounds are among the reported secondary metabolites of the Croton genus that are a potential source of bioactive compounds. This study evaluated the anxiolytic potential of clerodine-type diterpene, sonderianin (CBWS) isolated from the stem bark of C. blanchetianus and its mechanism of action in adult zebrafish (Danio rerio) (ZFa). The anticonvulsant and anti-acetylcholinesterase effects have also been explored. ZFa (n = 6/group) were treated intraperitoneally (ip; 20 µL) with CBWS (4, 12 and 40 mg/kg) and vehicle (3% DMSO; 20 µL) and subjected to locomotor activity tests, as well as toxicity acute 96 h. CBWS was also administered for analysis in the light/dark test. The involvement of the serotonergic system (5-HT) was investigated using 5-HTR1, 5-HTR2A/2C and 5-HTR3A/3B receptor antagonists. Anxiolytic doses were tested for pentylenetetrazol-induced seizure in ZFa. The inhibitory activity of the enzyme acetylcholinesterase (AChE) was measured. CBWS was not considered toxic and reduced locomotor activity. The results of the present study identified for the first time the interaction of the diterpene sonderianina in the CNS. This study provides evidence that CBWS has an anxiolytic effect mediated by serotonergic (5-HT) involvement and anti-acetylcholinesterase action. The 5-HTR1 and 5-HTR2A/2C receptors may be implicated in the low anticonvulsant effect in CBWS. Communicated by Ramaswamy H. Sarma

The aim of this study was to evaluate the anxiolytic-like effect of chrysophanol (CHRY), isolated from hexane extract of Senna cana stem and its possible mechanism of action. CHRY was obtained through chromatographic treatments and its identity was confirmed by uni and bidimensional RMN1H and RMN13C. Adult zebrafish (n = 6/group) were treated (with CHRY (4.0 or 12.0 or 40.0 mg/Kg; 20 µL; intraperitoneally) and submitted to acute toxicity and open field tests. Subsequently, other groups (n = 6/each) received CHRY for the analysis of its effect on the Light & Dark Test. The participation of the GABAergic system was also assessed using the diazepam (GABAA receptor agonist) and flumazenil (GABAA receptor antagonist). CHRY was considered non-toxic, it did not reduce the locomotor activity, and showed an anxiolytic-like effect. This effect was reduced by pre-treatment with flumazenil. The results suggest that CHRY is an anxiolytic-like agent mediated via the GABAergic system.

Antimicrobial resistance and the consequent inefficiency of antibiotics are the main problems faced by medicine. In view of this, numerous researches have been aimed at looking for new agents with antibacterial activity, among them natural products. Thus, this study aims to evaluate the antioxidant activity of aqueous and hydroalcoholic extracts of the leaves and roots of Spondias tuberosa by Thin Layer Chromatography (TLC), as well as to verify the antibacterial action of the extracts alone and in combination with commercial antibiotics to evaluate its potential in action of change of antibiotics. The extracts showed polar and nonpolar phenolic substances with antioxidant action. The Minimum Inhibitory Concentration (MIC) of the hydroalcoholic extracts of the leaves and roots was 1,024 μg/mL compared to the Staphylococcus aureus 25923 strain, whereas with the other strains, the products showed an MIC ≥ 2,048 µg/mL. The effect of combining extracts with amikacin, ampicillin and norfloxacin against the multidrug-resistant bacteria Escherichia coli 06, Staphylococcus aureus 10 and Pseudomonas aeruginosa 24 resulted in synergistic effects with aminoglycoside alone, achieving up to 75 % reduction in the MIC of the antibiotic. In view of the results obtained, it can be concluded that the extracts of S. tuberosa presented polar and nonpolar phenolic substances, in the antibacterial activity it can positively modify the effect of the aminoglycoside antibiotic against multi-resistant bacteria, but future studies are necessary to discover the mechanism of action of such an effect. La resistencia a los antimicrobianos y la consiguiente ineficacia de los antibióticos son los principales problemas a los que se enfrenta la medicina. Ante esto, numerosas investigaciones se han dirigido a buscar nuevos agentes con actividad antibacteriana, entre ellos productos naturales. Así, este estudio tiene como objetivo evaluar la actividad antioxidante de extractos acuosos e hidroalcohólicos de las hojas y raíces de Spondias tuberosa mediante Cromatografía de Capa Fina (CCF), así como verificar la acción antibacteriana de los extractos solos y en combinación con antibióticos comerciales para evaluar su potencial en la acción del cambio de antibióticos. Los extractos mostraron sustancias fenólicas polares y apolares con acción antioxidante. La Concentración Mínima Inhibitoria (CMI) de los extractos hidroalcohólicos de hojas y raíces fue de 1.024 μg / mL en comparación con la cepa Staphylococcus aureus 25923, mientras que con las otras cepas, los productos mostraron una CMI ≥ 2.048 µg / mL. El efecto de combinar extractos con amikacina, ampicilina y norfloxacina contra la bacteria multirresistente Escherichia coli 06, Staphylococcus aureus 10 y Pseudomonas aeruginosa 24 resultó en efectos sinérgicos con el aminoglucósido solo, logrando reducción de hasta un 75 % en la CMI del antibiótico. A la vista de los resultados obtenido, se puede concluir que los extractos de S. tuberosa presentó sustancias fenólicas polares y apolares, en el actividad antibacteriana puede modificar positivamente el efecto del antibiótico aminoglucósido contra bacterias multirresistentes, pero el futuro son necesarios estudios para descubrir el mecanismo de acción de tal efecto. A resistência antimicrobiana e a consequente ineficiência de antibióticos são os principais problemas enfrentados pela medicina. Diante disto, inúmeras pesquisas têm sido destinadas a procurar novos agentes com atividade antibacteriana, dentre eles os produtos naturais. Dessa forma, esse estudo tem como objetivo avaliar a atividade antioxidante dos extratos aquosos e hidroalcoólicos das folhas e raízes de S. tuberosa Arruda (umbu) por Cromatografia em Camada Delgada (CCD), bem como verificar a ação antibacteriana dos extratos isoladamente e em combinação com antibióticos comerciais para avaliar seu potencial na ação de modificação de antibióticos. Os extratos apresentaram substâncias fenólicas polares e apolares com ação antioxidante. A Concentração Inibitória Mínima (CIM) dos extratos hidroalcoólicos das folhas e raízes foi 1024 μg/mL frente a cepa Staphylococcus aureus 25923, já com as demais cepas os produtos demonstraram uma CIM ≥ 2.048 µg/mL. O efeito da combinação dos extratos com amicacina, ampicilina e norfloxacina frente às bactérias multirresistentes Escherichia coli 06, Staphylococcus aureus 10 e Pseudomonas aeruginosa 24 resultou em efeitos sinérgicos apenas com o aminoglicosídeo, alcançando até 75 % de redução da CIM do antibiótico. Diante dos resultados obtidos, pode-se concluir que os extratos de S. tuberosa apresentaram substâncias fenólicas polares e apolares, na atividade antibacteriana pode modificar positivamente o efeito do antibiótico aminoglicosídeo contra bactérias multirresistentes, mas estudos futuros é preciso para descobrir o mecanismo de ação de tal efeito.

Croton zehntneri is a plant known as canelinha de cunha, prevalent in the northeast region of Brazil. Many constituents of the vegetable have already been studied, and their pharmacological properties have been proven, but this is the first study to analyze the antinociceptive effect in adult zebrafish (ZFa) of the triterpene acetyl aleuritolic acid (AAA) isolated from the stem bark. The animals (ZFa; n = 6/group) were treated intraperitoneally (ip; 20 μL) with AAA (0.1 or 0.3 or 1.0 mg/mL) or vehicle (0.9% saline; 20 μL), and submitted to the locomotor activity test, as well as 96 h acute toxicity. Other groups (n = 6/each) received the same treatments and underwent acute nociception tests (formalin, cinnamaldehyde, glutamate, acid saline, capsaicin, and hypertonic saline). Possible neuromodulation mechanisms were evaluated. AAA (0.1 or 0.3 or 1.0 mg/mL) reduced the nociceptive behavior induced by acid saline and capsaicin, as well as inhibited corneal nociception induced by hypertonic saline, both without altering the animals’ locomotor system and without toxicity. These analgesic effects of AAA were significantly (p > 0.05) similar to those of morphine, used as a positive control. The antinociceptive effect of AAA was inhibited by methylene blue, ketamine, camphor, ruthenium red, amiloride, and mefenamic acid. The antinociceptive effect of AAA on the cornea of animals was inhibited by capsazepine. Therefore, AAA showed pharmacological potential for the treatment of acute pain, and this effect is modulated by cGMP, NMDA receptors, transient receptor potential channels (TRPs), ASICs and has pharmacological potential for the treatment of corneal pain modulated by the TRPV1 channel.

Drugs used to treat pain are associated with adverse effects, increasing the search for new drugs as an alternative treatment for pain. Therefore, we evaluated the antinociceptive behavior and possible neuromodulation mechanisms of triterpene 3β, 6β, 16β-trihydroxylup-20(29)-ene (CLF-1) isolated from Combretum leprosum leaves in zebrafish. Zebrafish (n = 6/group) were pretreated with CLF-1 (0.1 or 0.3 or 1.0 mg/mL; i.p.) and underwent nociception behavior tests. The antinociceptive effect of CFL-1 was tested for modulation by opioid (naloxone), nitrergic (L-NAME), nitric oxide and guanylate cyclase synthesis inhibitor (methylene blue), NMDA (Ketamine), TRPV1 (ruthenium red), TRPA1 (camphor), or ASIC (amiloride) antagonists. The corneal antinociceptive effect of CFL-1 was tested for modulation by TRPV1 (capsazepine). The effect of CFL-1 on zebrafish locomotor behavior was evaluated with the open field test. The acute toxicity study was conducted. CLF-1 reduced nociceptive behavior and corneal in zebrafish without mortalities and without altering the animals’ locomotion. Thus, CFL-1 presenting pharmacological potential for the treatment of acute pain and corneal pain, and this effect is modulated by the opioids, nitrergic system, NMDA receptors and TRP and ASIC channels.

Cashew apple extract (CAE) is a product with intense yellow color obtained from residual fibers of juice processing. Although CAE is known to be rich in carotenoids and anacardic acids, the biological activities of this potential natural food colorant remain unexplored. The present study is the first to investigate the toxicity, antiproliferative and antimicrobial activities of the lyophilized CAE (L-CAE) and its encapsulated products, using maltodextrin (M-CAE) or cashew gum (CG-CAE) as carriers. In addition to their high carotenoid content, the phenolic contents in all materials was determined using UPLC-QTOF-MS(E). The acute toxicity was performed using adult zebrafish (Danio rerio); antiproliferative activity was assessed using seven different human tumor cell lines [U-251 (glioblastoma), MCF-7 (breast, adenocarcinoma), NCI-ADR/RES (multidrug-resistant ovarian adenocarcinoma), NCI-H-460 (lung, large cell carcinoma), PC-3 (prostate, adenocarcinoma), OVCAR-3 (ovarian adenocarcinoma), and HT-29 (colon, adenocarcinoma)] and an immortalized human keratinocyte (HaCaT) while the antimicrobioal activity was evaluated on Staphylococcus aureus ATCC 25923, Listeria monocytogenes ATCC 19115, Escherichia coli ATCC 25922 and Salmonella Typhimurium ATCC 51812 microorganisms. Both lyophilized and encapsulated CAE samples did not exert acute toxicity against zebrafish neither antiproliferative effect against human tumor and non-tumor cell lines. Further, L-CAE showed potential antimicrobial activity against Listeria monocytogenes, which was confirmed using electron microscopy. The current findings demonstrated that CAE is a potential source of bioactive compounds to use as an additive in the food industry. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13197-020-04594-0) contains supplementary material, which is available to authorized users.

Background: Plant lectins have shown promising neuropharmacological activities in animal models. Objective: This study evaluated the effect of Dioclea altissima seed lectin (DAL) on adult zebrafish behavior. Method: Zebrafish (n=6/group) were treated (i.p.; 20 μL) with DAL (0.025; 0.05 or 0.1 mg/mL), vehicle or diazepam (DZP) and submitted to several tests (open field, light/dark preference or novel tank). Flumazenil, pizotifen or granisetron were administered 15 min before DAL (0.05 mg/mL), and the animals were evaluated on light/dark preference test. It was also verified whether the DAL effect depended on its structural integrity and ability to interact with carbohydrates. Results: DAL decreased the locomotor activity of adult zebrafish (0.025; 0.05 or 0.1 mg/mL), increased the time spent in the upper region of the aquarium (0.025 mg/mL), and decreased the latency time of adult zebrafish to enter the upper region on the novel tank test. DAL (0.05 mg/mL) also increased their permanence in the light zone of the light/dark preference test. The effect of DAL was dependent on carbohydrate interaction and protein structure integrity and was prevented by pizotifen, granizetron and flumazenil. Conclusion: DAL was found to have an anxiolytic-like effect mediated by the 5-HT and GABAergic receptors.

To ensure the antimicrobial activity of the aqueous extract of chambá, it is essential to protect its bioactive compounds. The objective was to preserve its characteristics, aiming to provide the food industry with a natural antimicrobial. Three microcapsule formulations made with maltodextrin and cyclodextrin were developed, both including the aqueous extract of chambá leaves dried through lyophilization. The aqueous extract was initially submitted to in vivo toxicity analysis using zebrafish and the microcapsules were characterized through studies of morphology, hygroscopicity, water solubility, particle size, zeta potential, color determination, microencapsulation efficiency and antimicrobial activity. The aqueous extract of chambá was not considered to be toxic. The microcapsules had irregular shapes, with sizes varying from 0.58 to 1.15 µm. Solubility values ranged from 74.69 to 76.8% and hygroscopicity varied from 2.07 to 4.34%. Additionally, it obtained efficient encapsulation of the phenolic compounds, showing antimicrobial activity against Staphylococcus aureus, Listeria monocytogenes, Salmonella Enteritidis and Escherichia coli, with its use being an alternative as a natural antimicrobial agent. RESUMO Para assegurar a atividade antimicrobiana do extrato aquoso de chambá é essencial proteger seus compostos bioativos. Objetivou-se preservar as suas características, visando proporcionar a indústria de alimentos um antimicrobiano natural. Três formulações de microcápsulas foram elaboradas com maltodextrina e ciclodextrina, ambas juntamente com o extrato aquoso de folhas de chambá e secas por liofilização. O extrato aquoso foi inicialmente submetido à análise de toxicidade in vivo utilizando zebrafish e as microcápsulas foram caracterizadas por estudo da morfologia, higroscopicidade, solubilidade em água, tamanho de partículas, potencial zeta, determinação da cor, eficiência da microencapsulação e atividade antimicrobiana. O extrato aquoso de chambá não foi considerado tóxico. As microcápsulas apresentaram formas irregulares, tamanhos variando de 0,58 a 1,15 µm. Valores de solubilidade de 74,69 a 76,8%. A higrocospicidade variou de 2,07 a 4,34 %. Além disso, obteve eficiente encapsulação dos compostos fenólicos, apresentando atividade antimicrobiana diante Staphylococcus aureus, Listeria monocytogenes, Salmonella Enteritidis e Escherichia coli, sendo uma alternativa sua utilização como antimicrobiano natural.

The aim of this study was to identify and evaluate the chemical compositions and effects of the S. tuberosa leaf and root hydroalcoholic extracts (HELST and HERST) against different strains of Candida. Chemical analysis was performed by Ultra-Performance Liquid Chromatography Coupled to Quadrupole/Time of Flight System (UPLC-MS-ESI-QTOF). The Inhibitory Concentration of 50% of the growth (IC50) as well as the intrinsic and combined action of the extracts with the antifungal fluconazole (FCZ) were determined by the microdilution method while the minimum fungicidal concentrations (MFCs) and the effect on fungal morphological transitions were analyzed by subculture and in humid chambers, respectively. From the preliminary phytochemical analysis, the phenols and flavonoids were the most abundant. The intrinsic IC50 values for HELST ranged from 5716.3 to 7805.8 &micro, g/mL and from 6175.4 to 51070.9 &micro, g/mL for the HERST, whereas the combination of the extracts with fluconazole presented IC50 values from 2.65 to 278.41 &micro, g/mL. The MFC of the extracts, individually, for all the tested strains was &ge, 16384 &micro, g/mL. When fluconazole was combined with each extract, the MFC against CA URM 5974 was reduced (HELST: 2048 and HERST: 4096 &micro, g/mL). Synergism was observed against standard C. albicans (CA) and C. tropicalis (CT) strains and with the root extract against the CT isolate. The leaf extract inhibited the morphological transition of all strains while the root extract inhibited only CT strains.