Envolvimento das vias de sinalização celular no efeito tipo-antidepressivo da quercetina em camundongos / Involvement of cellular signaling pathways in the antidepressant-like effect of quercetin in mice

A elevada prevalência do Transtorno Depressivo Maior (TDM) tem recebido atenção da comunidade científica pois acarreta considerável sofrimento aos acometidos. As bases neurobiológicas do TDM são pouco conhecidas e as opções de tratamento farmacológico disponíveis são escassas. Nesse sentido, investigar potenciais moléculas com efeito antidepressivo é crucial. A pesquisa objetivou elucidar o envolvimento das vias de sinalização celular no efeito tipo-antidepressivo da quercetina. Para isso, vários grupos de camundongos Swiss fêmeas foram tratados com veículo (solução salina 0,9% estéril), quercetina 25 mg/Kg (v.o.), inibidor (i.c.v.) ou quercetina + inibidor. Foram utilizados os inibidores: H-89 (inibidor da proteína cinase A, 1 µg/sítio, i.c.v.); KN-62 (inibidor da proteína cinase dependente de Ca2+/calmodulina, 1 µg/sítio, i.c.v.); LY294002, um inibidor da fosfatidilinositol 3 cinase (PI3K, 10 nmol/sítio, i.c.v.); e um inibidor da proteína cinase regulada por sinal extracelular (ERK), o PD98059 (5 µg/sítio, i.c.v.). Os animais foram submetidos ao Teste de Suspensão pela Cauda (TSC) e Teste do Aberto (TCA) para avaliação do efeito tipo-antidepressivo e possíveis interferências dos tratamentos na capacidade locomotora. Todos os procedimentos foram aprovados pelo CEUA/UNIVALI 021/2013. Os resultados obtidos apontaram que a quercetina foi capaz de reduzir o tempo de imobilidade dos camundongos no TSC, entretanto, sem comprometer a capacidade locomotora dos animais (TCA). Além disso, foi constatado que os inibidores H-89, KN-62, LY294002 e PD98059 revereteram o efeito anti-imobilidade da quercetina. A administração dos inibidores isolados ou em associação com a quercetina, não comprometeram a locomoção dos camundongos. De forma geral, os dados apontam que a quercetina desencadeia efeito tipo-antidepressivo por intermédio da modulação da proteína cinase A (PKA), proteína cinase dependente de Ca2+/calmodulina (CaMKII), fosfatidilinositol 3 cinase (PI3K) e proteína cinase regulada por sinal extracelular (MAPKs/ERK)

Avaliação de efeitos preliminares do plumierídeo após administração oral a camundongos / Evaluation of plumieride’s preliminary effects triggered by oral administration to mice

A pesquisa de moléculas oriundas do metabolismo secundário de plantas tem apresentado resultados promissores ao longo dos anos. Novas classes de compostos, como os iridoides, despertam interesse científico devido às suas propriedades farmacológicas. O plumierídeo (PLU), um iridoide isolado das flores de Allamanda cathartica, vem sendo estudado por nosso grupo de pesquisa quanto aos seus efeitos anti-inflamatório e antidepressivo após administração intraperitoneal. Entretanto, não há informações disponíveis na literatura sobre seus efeitos preliminares no SNC de camundongos após administração por via oral. Este trabalho objetivou a investigação dos possíveis efeitos pró-convulsivante ou anticonvulsivante do plumierídeo, além das possíveis interferências no sistema locomotor e emocionalidade de camundongos. Para tanto, os procedimentos foram aprovados pelo CEUA/UNIVALI (035/2016). Os testes de convulsão foram realizados através do tratamento de camundongos Swiss fêmeas com veículo, PLU (0,5, 1 e 2 µg/Kg, v.o.) e o fármaco fenobarbital (50 mg/Kg, i.p.), sendo posteriormente expostas aos agentes convulsivantes pentilenotetrazol (PTZ, 100 mg/Kg, i.p.) e estricnina (ESTR, 4 mg/Kg, i.p.). A capacidade de locomoção e equilíbrio foi testada em camundongos tratados com veículo ou PLU (0,5, 1 e 2 µg/Kg, v.o.) no Rota-Rod. Já a emocionalidade foi investigada através do teste do campo aberto (TCA). Quanto aos resultados, o iridoide não foi capaz de exercer efeito pró-convulsivante ou anticonvulsivante frente ao PTZ ou ESTR, diferentemente do fenobarbital. O mesmo também não diminuiu a mortalidade dos camundongos. A administração aguda por via oral das doses testadas não interferiu na capacidade locomotora, equilíbrio ou emocionalidade dos animais. Sugere-se que novos estudos sejam conduzidos com doses maiores do plumierídeo, entretanto, os dados da pesquisa são cruciais para fomentar as investigações farmacológicas subsequentes do iridoide

Antidepressant-like effect of caffeic acid: Involvement of the cellular signaling pathways

Caffeic acid is a phenolic compound widely distributed in plants and beverages such as coffee. Although its mechanism of action is poorly understood, caffeic acid reportedly induces antidepressant-like and neuroprotective effects. This study aimed to investigate the involvement of cellular signaling pathways in acute antidepressant-like effect induced by caffeic acid in mice. All procedures were approved by the Institutional Animal Ethics Committee of the UNIVALI n. 021/2013. Female Swiss mice were administered with vehicle, caffeic acid (5 mg/ kg, p.o.), inhibitor (H-89, U0126, chelerythrine, or PD9859, i.c.v.) or caffeic acid plus inhibitor. The behavioral effects were evaluated 1h after the administration of compounds to mice using tail suspension test (TST) and open field test (OFT). The results showed that the antidepressant- like effect of caffeic acid in mice was possibly mediated by the activation of PKA, MEK 1/2, PKC and MAPK (as assessed using TST), without compromising their locomotor activity (as assessed using OFT). Our results demonstrated, at least in part, the pathways involved in the neuroprotective and behavioral effects of caffeic acid

Avaliação psicofarmacológica do óleo essencial de Piper amplum

Made available in DSpace on 2018-02-15T18:27:44Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) priscila_laiz_et_all.pdf: 167157 bytes, checksum: af2a47b771e0098c144bfe77c462c921 (MD5) Previous issue date: 9Universidade do Vale do Itajaí. Itajaí, SC, Brasil.Universidade do Vale do Itajaí. Itajaí, SC, Brasil.Universidade do Vale do Itajaí. Itajaí, SC, Brasil.Universidade do Vale do Itajaí. Itajaí, SC, Brasil.Universidade do Vale do Itajaí. Itajaí, SC, Brasil.Universidade do Vale do Itajaí. Itajaí, SC, Brasil.Universidade do Vale do Itajaí. Itajaí, SC, Brasil.Universidade do Vale do Itajaí. Itajaí, SC, Brasil.Espécies do gênero Piper são utilizadas na medicina popular e carecem de validação farmacológica. Estudos científicos com a espécie Piper amplum são concentrados principalmente nos efeitos antimicrobianos e pouco se sabe sobre suas ações sobre o sistema nervoso central (SNC), apesar da planta ser utilizada de forma etnofarmacológica em processos neurológicos. Portanto, para avaliar os efeitos sobre o SNC, o óleo essencial obtido de Piper amplum (OEPA) (50, 100 150 mg/kg, v.o.) foi administrado em camundongos fêmeas Swiss (25-30 g/ n=8-10 animais e 60 minutos após os mesmos foram submetidos a testes de: depressão (teste do nado forçado, TNF), deambulação motora (campo aberto, TCA e Rotarod), convulsão e hipnose. Grupos controle-positivo (fármacos usados na terapêutica) e negativo (veículo no qual o OEPA foi dissolvido) foram utilizados nas mesmas condições experimentais. Os resultados demonstraram que o tratamento com OEPA não afetou a deambulação e atividade exploratória dos animais no TCA, assim como não afetou o sistema motor no Rotarod. Não foram detectados efeitos anticonvulsivante, hipnótico e ansiolítico do OEPA; entretanto, verificou-se atividade antidepressiva no TNF nas doses testadas. Diante dos efeitos do OEPA sobre o SNC, pode-se considerar o mesmo como alvo potencial para maiores estudos relacionados a atividade antidepressivaSpecies of the genus Piper used are in folk medicine and need pharmacological validation. Scientific studies with Piper amplum species are mainly concentrated on antimicrobial effects, little known is about their actions on the central nervous system (CNS), although the plant is ethnopharmacological used in neurological processes. Therefore, to evaluate the effects on the CNS, the essential oil obtained from Piper amplum (OEPA) (50, 100-150 mg/kg, p.o.) was administered in Swiss female mice (25-30 g/ n=8-10 animals) and 60 minutes after, the same were submitted to tests: depression forced swimming test, FST), motor ambulation (open field, OFT and Rotarod), seizure and hypnosis. Control-positive (drugs used in therapy) and negative (vehicle in which OEPA was dissolved) control groups were used under the same experimental conditions. The results showed that OEPA treatment did not affect the ambulation and exploratory activity of the animals in the OFT, and did not it affect the motor system in Rotarod. No anticonvulsive, hypnotic and anxiolytic effects of OEPA detected were, however, antidepressant activity in TNF at all doses tested. In view of the effects demonstrated by the OEPA on the CNS, it be can considered the same as a potential target for further studies related to antidepressant activity

Preconception exposure to malathion and glucose homeostasis in rats: Effects on dams during pregnancy and post-term periods, and on their progeny

Understanding the individual and global impact of pesticides on human physiology and the different stages of life is still a challenge in environmental health. We analyzed here whether administration of the organophosphate insecticide malathion before pregnancy could affect glucose homeostasis during pregnancy and, in addition, generate possible later consequences in mothers and offspring. For this, adult Wistar rats were allocated into two groups and were treated daily (intragastric) with malathion (14 or 140 mg/kg, body mass (bm)) for 21–25 days. Corn oil was used as vehicle in the Control group. Subgroups were defined based on the absence (nulliparous) or presence (pregnant) of a copulatory plug. Pregnant rats were followed by an additional period of 2 months after the term (post-term), without continuing malathion treatment. Fetuses and adult offspring of males and females were also evaluated. We ran an additional experimental design with rats exposed to malathion before pregnancy at a dose of 0.1 mg/kg bm. Malathion exposure resulted in glucose intolerance in the mothers during pregnancy and post-term period, regardless of the exposure dose. This was accompanied by increased visceral adipose tissue mass, dyslipidemia, unchanged pancreatic β-cell mass, and varying insulin responses to glucose in vivo. The number of total newborns and birthweight was not affected by malathion exposure. Adult offspring from both sexes also became glucose-intolerant, regardless of the pesticide dose their dams were exposed to. This alteration could be associated with changes at the epigenomic level, as reduced hepatic mRNA content of DNA methylases and demethylases was found. We demonstrated that periconceptional exposure to malathion with doses aiming to mimic from work environment to indirect contamination predisposes progenitors and offspring rats to glucose intolerance. Thus, we conclude that subchronic exposure to malathion is a risk factor for gestational diabetes and prediabetes later in life.We are indebted with the staff from the LIDoC and LAMEB. This research was partially granted by the National Council for Scientific and Technological Development (CNPq; grant number 428023/2018–5). In addition, some reagents and materials were acquired by A.R private funding or result from donations from collaborators. This work was submitted as thesis by M.A.B. M.A.B and F.N.S received a scholarship from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) – Finance Code 001, and P.L.Z received a scholarship from the CNPq. A.R is funded by a CNPq research grant (grant number 304388/2020–3). IQ is funded by a grant of Generalitat Valenciana (PROMETEO/2020/006)

Antimicrobial (including antimollicutes), antioxidant and anticholinesterase activities of Brazilian and Spanish marine organisms – evaluation of extracts and pure compounds

This work describes the antimicrobial, antioxidant and anticholinesterase activities in vitro of organic extracts from fourteen seaweeds, eleven sponges, two ascidians, one bryozoan, and one sea anemone species collected along the Brazilian and Spanish coast, as well as the isolation of the diterpene (4R, 9S, 14S)-4α-acetoxy-9β,14α-dihydroxydolast-1(15),7-diene (1) and halogenated sesquiterpene elatol (2). The most promising antimicrobial results for cell wall bacteria were obtained by extracts from seaweeds Laurencia dendroidea and Sargassum vulgare var. nanun (MIC 250 μg/ml), and by the bryozoan Bugula neritina (MIC 62.5 μg/ml), both against Staphylococcus aureus. As for antimollicutes, extracts from seaweeds showed results better than the extracts from invertebrates. Almost all seaweeds assayed (92%) exhibited some antimicrobial activity against mollicutes strains (Mycoplasma hominis, Mycoplasma genitalium, Mycoplasma capricolum and Mycoplasma pneumoniae strain FH). From these seaweeds, A1 (Canistrocarpus cervicornis), A11 (Gracilaria sp.) and A4 (Lobophora variegata) showed the best results for M. pneumoniae strain FH (MIC 250 μg/ml). Furthermore, compounds 1 and 2 were also assayed against mollicutes strains M. hominis, M. genitalium, M. capricolum, M. pneumoniae strain 129 and M. pneumoniae strain FH, which showed MIC > 100 μg/ml. Antioxidant activities of extracts from these marine organisms were inactive, except for E7 (from sponge Ircinia sp.), which exhibited moderated antioxidant activities for two methods assayed (IC50 83.0 ± 0.1 μg/ml, and 52.0 ± 0.8 mg AA/g, respectively). Finally, for the anticholinesterase activity, all the 29 samples evaluated (100%) exhibited some level of activity, with IC50 < 1000 μg/ml. From these, seaweeds extracts were considered more promising than marine invertebrate extracts [A10 (IC50 14.4 ± 0.1 μg/ml), A16 (IC50 16.4 ± 0.4 μg/ml) and A8 (IC50 14.9 ± 0.5 μg/ml)]. The findings of this work are useful for further research aiming at isolation and characterization of active compounds. Keywords: Elatol, Dolastane diterpene, Antimollicutes activity, Antioxidant activity, Anticholinesterase activit