RESUMO
Piper solmsianum C.DC., which is popularly known as pariparoba, is a shrub that measures 1-3 m in height and it inhabits areas with wet tropical soils. The objective of this study was to analyze the leaf and stem anatomy using light microscopy, scanning electron micrographs, and energy-dispersive X-ray spectroscopy in order to provide information for species identification. The anatomical profile showed the following main microscopic markers: hypostomatic leaf; hypodermis layer on both sides; pearl glands; biconvex midrib shape; five collateral vascular bundles in open arc with the central bundle larger than the others; circular stem shape; collateral vascular bundles arranged in two rings; sinuous sclerenchymatic sheath in the pith; secretory idioblasts; and starch grains in the mesophyll, in the ground parenchyma of the midrib, petiole, and in the stem; and six morphotypes of calcium oxalate crystals (styloids, cuneiform, tabular crystal rosettes, cuneiform crystal rosettes, elongated square dipyramids, as well as very elongated square dipyramids).
Assuntos
Piper/ultraestrutura , Folhas de Planta/ultraestrutura , Caules de Planta/ultraestrutura , Microscopia Eletrônica de Varredura , Piper/química , Folhas de Planta/química , Caules de Planta/química , Espectrometria por Raios XRESUMO
Recent studies have shown that gallic acid and its alkylesters induce apoptosis in different cell lines. Since new compounds with biological activity and less cytotoxicity to normal cells are necessary for cancer therapy, the aim of this study was to evaluate the cytotoxic effect of 1-(3,4,5-trihydroxyphenyl)-dodecylbenzoate on human acute myeloid leukemia K562 cells and on human acute lymphoblastic leukemia Jurkat cells. The cell viability was determined by MTT method. The apoptosis induction was assessed by bromide and acridine orange staining and by Annexin V-FITC Apoptosis Detection kit. The cell cycle analysis was carried out by flow cytometry using propidium iodide. Cytometric analysis was also performed to evaluate the expression of the following proteins: AIF, p53, Bcl-2 and Bax. The mitochondrial potential was also assessed by flow cytometry using MitoView633 kit. The results showed that the compound significantly reduced the cell viability of K562 and Jurkat cells in a concentration and time dependent manner (IC50 of 30 µM). The compound induced cell cycle arrest in G0/G1phase and significantly increased the proportion of cells in the sub-G0/G1phase. Apoptosis was confirmed by the sight of morphological characteristics of apoptosis and by phosphatidylserine externalization (73.47±5.71% of cells expressing annexin). The results also showed that the compound promotes a modification in Bax:Bcl-2 ratio and increases p53 expression. Thus, it is possible to conclude that 1-(3,4,5-trihydroxyphenyl)-dodecylbenzoate induces apoptosis by inhibiting the antiapoptotic protein Bcl-2 and by increasing the release of AIF, Bax and p53. In addition, it blocks the cell cycle at G0/G1, stopping cell proliferation. So far, the results suggest that this compound may have a potential therapeutic effect against leukemia cells.
RESUMO
The hypothalamic release of glutamate and GABA regulates neurosecretory functions that may control the onset of puberty. This release may be influenced by neurosteroids such as allopregnanolone. Using superfusion experiments we examined the role of allopregnanolone on the K(+)-evoked and basal [(3)H]-glutamate and [(3)H]-GABA release from mediobasal hypothalamus and anterior preoptic area in prepubertal, vaginal opening and pubertal (P) rats and evaluated its modulatory effect on GABAA and NMDA (N-methyl-d-aspartic acid) receptors. Also, we examined the hypothalamic activity and mRNA expression of 3α-hydroxysteroid oxidoreductase (3α-HSOR) - enzyme that synthesizes allopregnanolone - using a spectrophotometric method and RT-PCR, respectively. Allopregnanolone increased both the K(+)-evoked [(3)H]-glutamate and [(3)H]-GABA release in P rats, being the former effect mediated by the modulation of NMDA receptors - as was reverted by Mg(2+) and by the NMDA receptor antagonist AP-7 and the latter by the modulation of NMDA and GABAA receptors - as was reverted by Mg(2+) and the GABAA receptor antagonist bicuculline. The neurosteroid also increased the basal release of [(3)H]-glutamate in VO rats in an effect that was dependent on the modulation of NMDA receptors as was reverted by Mg(2+). On the other hand we show that allopregnanolone reduced the basal release of [(3)H]-GABA in P rats although we cannot elucidate the precise mechanism by which the neurosteroid exerted this latter effect. The enzymatic activity and the mRNA expression of 3α-HSOR were both increased in P rats regarding the other two studied stages of sexual development. These results suggest an important physiological function of allopregnanolone in the hypothalamus of the P rat where it might be involved in the 'fine tuning' of neurosecretory functions related to the biology of reproduction of the female rats.
Assuntos
3-alfa-Hidroxiesteroide Desidrogenase (B-Específica)/biossíntese , Ácido Glutâmico/metabolismo , Hipotálamo/metabolismo , Pregnanolona/metabolismo , Maturidade Sexual/fisiologia , Ácido gama-Aminobutírico/metabolismo , Animais , Feminino , Neurotransmissores/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Steroids synthesized in the central nervous system are termed "neurosteroids". They are synthesized and metabolized in several brain areas. The objective of this work was to determine if 1 intracerebroventricular allopregnanolone injection in rats can interfere in luteal regression in a close relationship with modifications in LH, progesterone, and prolactin serum concentrations. Allopregnanolone was injected during proestrus morning and the animals were sacrificed on oestrous morning. Ovulation test and histological analysis were performed in the oestrus morning with light and electron microscopy. Serum prolactin, LH, and progesterone levels were measured by radioimmunoassay. The allopregnanolone injection significantly decreased luteinizing hormone serum level and the number of oocytes on oestrus. Progesterone and prolactin serum levels were increased after this injection. The inhibition of apoptotic figures due to allopregnanolone administration was detected in the already formed corpora lutea belonging to the previous ovary cycle and it was significantly lower than in vehicle group (control). When the GABA(A) antagonist (bicuculline) was administered alone or previously to allopregnanolone, no effect on the ovulation rate was observed. No changes in the apoptotic cell numbers were observed with respect to those of vehicle group. These results show that the effect of centrally injected allopreganolone over reproductive function could be due to a centrally originated LH mediated effect over ovarian function that affects luteal regression, through the inhibition of apoptosis and stimulation of progesterone and prolactin release.
Assuntos
Apoptose/efeitos dos fármacos , Hormônio Luteinizante/sangue , Pregnanolona/farmacologia , Progesterona/sangue , Prolactina/sangue , Animais , Contagem de Células , Corpo Lúteo/citologia , Corpo Lúteo/efeitos dos fármacos , Corpo Lúteo/ultraestrutura , Feminino , Oócitos/citologia , Oócitos/efeitos dos fármacos , Pregnanolona/administração & dosagem , Ratos , Ratos Sprague-DawleyRESUMO
In the present study, we describe the antinociceptive effect of filicene, a triterpene isolated from Adiantum cuneatum (Adiantaceae) leaves, in several models of pain in mice. When evaluated against acetic acid-induced abdominal constrictions, filicene (10, 30 and 60 mg/kg, i.p.) produced dose-related inhibition of the number of constrictions, being several times more potent [ID(50)=9.17 (6.27-13.18) mg/kg] than acetaminophen [ID(50)=18.8 (15.7-22.6) mg/kg], diclofenac [ID(50)=12.1(9.40-15.6) mg/kg] and acetylsalicylic acid [ID(50)=24.0(13.1-43.8) mg/kg] in the same doses as those used for the standard drugs. Filicene also produced dose-related inhibition of the pain caused by capsaicin and glutamate, with mean ID(50) values of 11.7 (8.51-16.0) mg/kg and <10 mg/kg, respectively. Its antinociceptive action was significantly reversed by atropine, haloperidol, GABA(A) and GABA(B) antagonists (bicuculline and phaclofen, respectively), but was not affected by L-arginine-nitric oxide, serotonin, adrenergic and the opioid systems. Together, these results indicate that the mechanisms involved in its action are not completely understood, but seem to involve interaction with the cholinergic, dopaminergic, glutamatergic, GABAergic and tachykinergic systems.
Assuntos
Adiantum/química , Analgésicos/isolamento & purificação , Analgésicos/farmacologia , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Ácido Acético/toxicidade , Analgésicos/administração & dosagem , Analgésicos/química , Animais , Capsaicina/toxicidade , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ácido Glutâmico/toxicidade , Masculino , Camundongos , Estrutura Molecular , Dor/tratamento farmacológico , Dor/fisiopatologia , Fitoterapia , Plantas Medicinais/química , Receptores Colinérgicos/efeitos dos fármacos , Receptores Colinérgicos/fisiologia , Receptores Dopaminérgicos/efeitos dos fármacos , Receptores Dopaminérgicos/fisiologia , Receptores de GABA/efeitos dos fármacos , Receptores de GABA/fisiologia , Receptores de Neurotransmissores/efeitos dos fármacos , Receptores de Neurotransmissores/fisiologia , Receptores de Taquicininas/efeitos dos fármacos , Receptores de Taquicininas/fisiologia , Triterpenos/administração & dosagem , Triterpenos/químicaRESUMO
The antifungal activity of a complete series of 15 n-alkyl gallates and six analogues acting against a representative panel of opportunistic pathogenic fungi was studied in order to analyze their role in: the importance of the fungi tested, the importance of the hydroxyls, the influence of the chain length and the hydrophobicity of the compounds. It was demonstrated that dermatophytes were the most susceptible species and that hydroxyls appear to be necessary but not sufficient for the activity. When the logP of each gallate was calculated and related to the different values of MIC against Microsporum gypseum it was observed that hexyl, heptyl, octyl and nonyl gallates exhibit a significant positive deviation from the curve corresponding to a polynomial equation obtained for the other gallates. This suggests that these compounds have a further mode of action besides their hydrophobicity, possibly the inhibition of some enzyme involved in ergosterol biosynthesis.
Assuntos
Antifúngicos/síntese química , Antifúngicos/farmacologia , Química Farmacêutica/métodos , Fungos/efeitos dos fármacos , Ácido Gálico/análogos & derivados , Arthrodermataceae/metabolismo , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Ergosterol/química , Ácido Gálico/química , Testes de Sensibilidade Microbiana , Microsporum/metabolismo , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Three new triterpenes, 2alpha-acetoxy-3beta,19alpha-dihydroxy-11alpha,12alpha-epoxy-ursan-28,13beta-olide, 3beta-acetoxy-2alpha,19alpha-dihydroxy-11alpha,12alpha-epoxy-ursan-28,13beta-olide and 2-O-acetyl-euscaphic acid together eight known triterpenes were isolated from the roots and stems of Cecropia catharinensis. Their structures were determined by detailed analysis of NMR spectra and the relative configurations established by difference nOe experiments. In addition, four flavonoid glucosides (vitexin, isovitexin, orientin and isoorientin) were found in the leaves.
Assuntos
Cecropia/química , Plantas Medicinais/química , Triterpenos/isolamento & purificação , Brasil , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Folhas de Planta/química , Raízes de Plantas/química , Estereoisomerismo , Triterpenos/químicaRESUMO
OBJECTIVES: Progesterone modulates dopamine (DA) release in corpus striatum. Our objective was to evaluate the effect of the i.c.v injection of the neurosteroid allopregnanolone (ALL), a progesterone metabolite on dopaminergic activity in the corpus striatum of rats under different gonadal hormonal conditions. METHODS: We have measured the concentrations of DOPA, DA and DOPAC (main metabolite of DA) in the corpus striatum in estrus and diestrus rats and in ovariectomized rats without hormonal replacement (OVX group) and primed with estrogen and progesterone (OVX(i) group). Additionally, we have used the aromatic acid decarboxylase inhibitor NSD in order to evaluate the function of tyrosine hydroxylase (TH), the rate-limiting enzyme of dopamine synthesis. RESULTS: ALL significantly decreased the striatal concentrations of both DA and DOPAC in the estrus. On the other hand, ALL increased significantly the levels of DA in the OVX(i) group. The DOPA accumulation in OVX(i) after NSD treatment in the ALL-treated groups was greater than in the vehicle group. However, the estrus group did not modify the DOPA accumulation after NSD injection. DISCUSSION: Our results suggest that ALL could modulate the dopaminergic transmission in the corpus striatum by causing changes in the activity of TH and/or in the pre- and post-synaptic dopaminergic terminals in the corpus striatum. This neurosteroidal mechanism could be a new kind of neurotransmitter systems modulation accomplished on TH activity itself and/or on the second messengers not related to ionic channels. Additionally, our results reinforce the idea of a close relationship between the fast non-genomic mechanism of ALL and the genomic actions of estrogen and progesterone.
Assuntos
Corpo Estriado/efeitos dos fármacos , Dopamina/metabolismo , Hormônios Gonadais/fisiologia , Pregnanolona/farmacologia , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Análise de Variância , Anestésicos , Animais , Di-Hidroxifenilalanina/metabolismo , Ciclo Estral , Feminino , Atividade Motora/efeitos dos fármacos , Ovariectomia/métodos , Ratos , Ratos Sprague-Dawley , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Marrubiin, a furane labdane diterpene, is the main analgesic compound present in Marrubium vulgare, a medicinal plant used in Brazil and other countries to treat several ailments. Considering its important pharmacological action, as well as its high yield, some structural modifications were performed in order to obtain more active compounds. Success was obtained in reducing the lactonic function, in the formation of marrubiinic acid and two esterified derivatives, which exhibited significant analgesic effect against the writhing test in mice. Marrubiinic acid showed better activity and excellent yield, and its analgesic effect was confirmed in other experimental models of pain in mice, suggesting its possible use as a model to obtain new and potent analgesic agents.
Assuntos
Analgésicos/síntese química , Diterpenos/síntese química , Marrubium/química , Analgésicos/isolamento & purificação , Analgésicos/uso terapêutico , Animais , Modelos Animais de Doenças , Diterpenos/isolamento & purificação , Diterpenos/uso terapêutico , Masculino , Camundongos , Estrutura Molecular , Dor/tratamento farmacológico , Folhas de Planta/química , Relação Estrutura-AtividadeRESUMO
Continuing our search for antinociceptive agents from natural sources, this study analyzed the antinociceptive effects of some fractions obtained from different parts (roots, flowers and fruits) of Calophyllum brasiliense, a Brazilian medicinal plant used to treat several diseases, including inflammation and pain. For this purpose, the writhing and formalin induced-pain models in mice were used. We also analyzed the chemical composition of these different parts and tested two pure compounds isolated from chloroform fraction (roots) identified as friedelin (1) and 1,5-dihydroxyxanthone (3), by direct comparison with authentic samples. The results showed that some fractions and both compounds exhibited considerable antinociception properties, particularly against the writhing test, and that these are more potent than acetyl salicylic acid and acetaminophen, two reference drugs used here for comparison.
Assuntos
Analgésicos não Narcóticos/farmacologia , Calophyllum/química , Acetaminofen/farmacologia , Ácido Acético , Analgésicos não Narcóticos/química , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/farmacologia , Clorofórmio , Cromatografia em Camada Fina , Flores/química , Formaldeído , Frutas/química , Indometacina/farmacologia , Metanol , Camundongos , Medição da Dor/efeitos dos fármacos , Extratos Vegetais/farmacologia , Raízes de Plantas/química , SolventesRESUMO
Wedelia paludosa (Acmela brasiliensis) (Asteraceae), a traditionally used native Brazilian medicinal plant, showed antifungal activity against dermatophytes in dilution tests. The hexane, dichloromethane and butanol fractions displayed activity against Epidermophyton floccosum, Trichophyton rubrum and Trichophyton mentagrophytes, with minimal inhibitory concentrations between 250 and 1000 microg/mL. Two pure compounds, identified as kaurenoic acid (1) and luteolin (2), also showed activity against these dermatophytes.
Assuntos
Antifúngicos/farmacologia , Fungos/efeitos dos fármacos , Wedelia/química , Antifúngicos/isolamento & purificação , Meios de Cultura , Diterpenos/farmacologia , Flavonoides/farmacologia , Flores/química , Luteolina , Metanol , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
Three sterols, 5alpha-ergost-7-en-3beta-ol, 5alpha-ergosta-7,22-dien-3beta-ol and 5,8-epidioxy-5alpha,8alpha-ergosta-6,22-dien-3beta-ol and five triterpenes, applanoxidic acids A, C, F, G and H, have been isolated from Ganoderma annulare. The applanoxidic acids A, C and F were found to inhibit the growth of the fungi Microsporum cannis and Trichophyton mentagrophytes at concentrations of 500 to 1000 microg/ml.
Assuntos
Antifúngicos/farmacologia , Ganoderma , Microsporum/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Trichophyton/efeitos dos fármacos , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Relação Dose-Resposta a Droga , Humanos , Testes de Sensibilidade Microbiana , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Esteróis/administração & dosagem , Esteróis/farmacologia , Esteróis/uso terapêutico , Triterpenos/administração & dosagem , Triterpenos/farmacologia , Triterpenos/uso terapêutico , MadeiraRESUMO
Our objective was to study the incidence of sperm-tail phosphotyrosine immunoreactivity in normozoospermic and asthenozoospermic human sperm samples, its association with sperm motion parameters, particularly hyperactivated motility, and its potential involvement in the pathogenesis of asthenozoospermia. The work was conducted as a prospective experimental study in the Sperm Biology and Andrology laboratories of the Jones Institute, a medical school-based fertility center. The study subjects were healthy fertile male donors (normozoospermic samples) and infertile patients (asthenozoospermic samples) attending the center. Recently ejaculated semen samples were washed twice to eliminate seminal plasma and a swim-up was performed to select the motile population which, in turn, was incubated up to 18 h at 37 degrees C in 3.5% human serum albumin-supplemented Hams F10 to allow for capacitation. For evaluation, sperm aliquots were taken pre-swim-up (T0), immediately post swim-up (T1), at 6 h (T6), and 18 h (T18) of incubation. The main outcome measures were computer-analyzed sperm motion parameters and hyperactivated motility, and immunodetection of phosphotyrosine (PY)-containing proteins. During the capacitating incubation, normozoospermic samples displayed maximum motility, velocity, and hyperactivation at T6, significantly decreasing their values at T18. PY-proteins were located both at the tail and head of spermatozoa. Their expression increased progressively during the incubation, being present in about 70% of the sperm tails at T18. Asthenozoospermic samples showed an inability to respond to capacitation with an increase in motion parameters and PY-phosphorylation. At T6, both hyperactivation and PY-phosphorylation were significantly lower than in normal samples. Our results suggest that PY-phosphorylation of tail proteins is highly conspicuous in human spermatozoa, and increases its incidence in a time-dependent manner, as more sperm become capacitated. Asthenozoospermic samples displaying low percentages of motile sperm and altered motion characteristics showed a decreased incidence of PY-phosphorelated sperm. Tail protein PY-phosphorylation may be related to sperm movement, especially to hyperactivated motility and its deficiency may be associated to asthenozoospermia. (AU)
Assuntos
Estudo Comparativo , Humanos , Masculino , RESEARCH SUPPORT, NON-U.S. GOVT , Infertilidade Masculina , Motilidade dos Espermatozoides/fisiologia , Cauda do Espermatozoide/metabolismo , Espermatozoides/metabolismo , Tirosina/metabolismo , Fosforilação , Capacitação Espermática , Fatores de TempoRESUMO
Our objective was to study the incidence of sperm-tail phosphotyrosine immunoreactivity in normozoospermic and asthenozoospermic human sperm samples, its association with sperm motion parameters, particularly hyperactivated motility, and its potential involvement in the pathogenesis of asthenozoospermia. The work was conducted as a prospective experimental study in the Sperm Biology and Andrology laboratories of the Jones Institute, a medical school-based fertility center. The study subjects were healthy fertile male donors (normozoospermic samples) and infertile patients (asthenozoospermic samples) attending the center. Recently ejaculated semen samples were washed twice to eliminate seminal plasma and a swim-up was performed to select the motile population which, in turn, was incubated up to 18 h at 37 degrees C in 3.5% human serum albumin-supplemented Ham's F10 to allow for capacitation. For evaluation, sperm aliquots were taken pre-swim-up (T0), immediately post swim-up (T1), at 6 h (T6), and 18 h (T18) of incubation. The main outcome measures were computer-analyzed sperm motion parameters and hyperactivated motility, and immunodetection of phosphotyrosine (PY)-containing proteins. During the capacitating incubation, normozoospermic samples displayed maximum motility, velocity, and hyperactivation at T6, significantly decreasing their values at T18. PY-proteins were located both at the tail and head of spermatozoa. Their expression increased progressively during the incubation, being present in about 70% of the sperm tails at T18. Asthenozoospermic samples showed an inability to respond to capacitation with an increase in motion parameters and PY-phosphorylation. At T6, both hyperactivation and PY-phosphorylation were significantly lower than in normal samples. Our results suggest that PY-phosphorylation of tail proteins is highly conspicuous in human spermatozoa, and increases its incidence in a time-dependent manner, as more sperm become capacitated. Asthenozoospermic samples displaying low percentages of motile sperm and altered motion characteristics showed a decreased incidence of PY-phosphorelated sperm. Tail protein PY-phosphorylation may be related to sperm movement, especially to hyperactivated motility and its deficiency may be associated to asthenozoospermia.
Assuntos
Humanos , Masculino , Cauda do Espermatozoide/metabolismo , Espermatozoides/metabolismo , Infertilidade Masculina , Motilidade dos Espermatozoides/fisiologia , Tirosina/metabolismo , Fosforilação , Capacitação Espermática , Fatores de TempoRESUMO
The lipid-lowering action of the leaves of the Aleurites moluccana methanol extract was studied in Triton W-1339 and high-fat-diet fed rats. The serum lipids (total cholesterol, LDL- and HDL-cholesterol and triglycerides) and body weight were found to be lowered by A. moluccana (300 mg/kg, b.w.) in rats with Triton-induced hypercholesterolaemia and on a hyperlipaemic diet. The results suggest that the lipid lowering action of this natural product is mediated through inhibition of hepatic cholesterol biosynthesis and reduction of lipid absorption in the intestine.
Assuntos
Aleurites , Hipolipemiantes/farmacologia , Lipídeos/sangue , Fitoterapia , Extratos Vegetais/farmacologia , Animais , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Gorduras na Dieta/administração & dosagem , Hipercolesterolemia/induzido quimicamente , Hipercolesterolemia/tratamento farmacológico , Hipolipemiantes/administração & dosagem , Hipolipemiantes/uso terapêutico , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Folhas de Planta , Polietilenoglicóis , Ratos , Ratos Wistar , Triglicerídeos/sangueRESUMO
Rubus imperialis is a Brasilian medicinal plant which previously exhibited therapeutical perspectives. This work describes the antinociceptive action of methanolic extracts obtained from different parts of the plant (roots and branches) as well as hexane, chloroform and ethyl acetate fractions obtained from branches. Such extracts or fractions caused significative inhibition in the writhing test in mice at 10 mg/kg, given intraperitoneally. They were more active than two reference drugs, aspirin and paracetamol. The fractions also exhibited antinociceptive activity in the writhing test when administered orally at 200 mg/kg. When analyzed in the formalin test, the chloroform fraction was the most active, causing considerable inhibition against both neurogenic and inflammatory phases of pain.
Assuntos
Analgésicos/farmacologia , Rosaceae/química , Ácido Acético , Animais , Formaldeído , Masculino , Camundongos , Medição da Dor/efeitos dos fármacos , Extratos Vegetais/farmacologia , SolventesRESUMO
Drimanial, a new sesquiterpene isolated from the barks of the plant Drimys winteri (Winteraceae), given systemically, intraplantarly, or by spinal or supraspinal routes, produced pronounced antinociception against both phases of formalin-induced licking. The systemic injection of drimanial also inhibited, in a graded manner, the pain-related behaviours induced by intraplantar or intrathecal (i.t.) administration of glutamate. Moreover, drimanial also caused marked inhibition of the nociception induced by i.t. administration of a metabotropic glutamate agonist (1S,3R)-ACPD, without affecting nociceptive responses induced by ionotropic agonists (NMDA, kainate, AMPA) or by substance P. The antinociception caused by drimanial was not influenced by naloxone, nor did it interfere with the motor coordination of animals in the rota-rod test. Furthermore, drimanial caused graded inhibition of [(3)H]glutamate binding in cerebral cortical membranes from mice, with an IC(50) value of 4.39 micro M. Together, these results provide strong evidence indicating that the sesquiterpene drimanial produces antinociception in mice at peripheral, spinal and supraspinal sites. An interaction with metabotropic glutamate receptors seems to contribute to the mechanisms underlying its antinociceptive action.
Assuntos
Analgésicos/farmacologia , Receptores de Glutamato/efeitos dos fármacos , Sesquiterpenos/farmacologia , Analgésicos Opioides/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Drimys/química , Aminoácidos Excitatórios/administração & dosagem , Aminoácidos Excitatórios/farmacologia , Formaldeído , Ácido Glutâmico/metabolismo , Injeções Espinhais , Masculino , Camundongos , Morfina/farmacologia , Medição da Dor/efeitos dos fármacos , Equilíbrio Postural/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , Desempenho Psicomotor/fisiologia , Substância P/administração & dosagem , Substância P/farmacologiaRESUMO
The present study describes the phytochemical analysis and analgesic activity of Curcuma zedoaria rhizomes grown in Brazil. The results showed that the hydroalcoholic extract, fractions, specially dichloromethane, and a pure compound, denoted as curcumenol (1), exhibited potent and dose-related analgesic activity when evaluated in several models of pain in mice, including writhing, formalin and capsaicin. Compound (1), which seems to be the main active principle from this plant, presented promising analgesic effects, being several times more potent than different reference drugs evaluated in the same experimental models. The calculated ID50 values (micromol/kg, i.p) were 22 and 12 when evaluated in writhing and capsaicin tests, respectively, and 29 micromol/kg in relation to the second phase of the formalin model. The lack of effect in the hot plate test suggests that (1) act by a mechanism which do not involves the participation of the opioid system. The phytochemical analysis indicated that the chemical composition of the plant grown in Brazil is similar to that grown in other countries. The results confirm and justify the popular use of this plant for the treatment of dolorous processes.
Assuntos
Analgésicos/farmacologia , Curcuma/química , Extratos Vegetais/farmacologia , Analgésicos/química , Animais , Brasil , Relação Dose-Resposta a Droga , Camundongos , Extratos Vegetais/químicaRESUMO
The interaction between Rab3A and calmodulin is necessary for the inhibitory effect of Rab3A in neuroendocrine cells. Contrastingly, Rab3A triggers the exocytosis known as acrosome reaction in permeabilized spermatozoa. Here we show that a Rab3A mutant that cannot bind calmodulin was fully capable of triggering acrosomal exocytosis. Additionally, calmodulin by itself abrogated the exocytosis triggered by Rab3A. The effect was observed with both the wild type protein and the calmodulin binding deficient mutant. Our results indicate that the inhibitory and stimulatory effects of Rab3A in different exocytic processes are mediated by different effectors.
Assuntos
Reação Acrossômica/fisiologia , Calmodulina/metabolismo , Exocitose/fisiologia , Proteína rab3A de Ligação ao GTP/metabolismo , Reação Acrossômica/efeitos dos fármacos , Calcimicina/farmacologia , Calmodulina/antagonistas & inibidores , Calmodulina/farmacologia , Permeabilidade da Membrana Celular , Clorpromazina/farmacologia , Antagonistas de Dopamina/farmacologia , Inibidores Enzimáticos/farmacologia , Exocitose/efeitos dos fármacos , Corantes Fluorescentes , Humanos , Ionóforos/farmacologia , Masculino , Mutação , Progesterona/farmacologia , Ligação Proteica/fisiologia , Espermatozoides/citologia , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Proteína rab3A de Ligação ao GTP/genética , Proteína rab3A de Ligação ao GTP/farmacologiaRESUMO
A methanolic extract and two fractions (n-hexane and ethyl acetate) from Virola oleifera leaves and some compounds (one lignan and two flavonoids) were investigated to verify the analgesic activity by using the writhing test in mice. The crude methanolic extract showed a moderate analgesic effect (about 40% of inhibition in this test at 10 mg/kg), whereas n-hexane and ethyl acetate fractions caused inhibition of 51.3 +/- 5.9% and 50.5 +/- 6.3%, respectively. Oleiferin-C (1), a lignan isolated from the n-hexane fraction, showed an interesting analgesic potential in this model when compared to two standard drugs, paracetamol (4-acetamidophenol) and aspirin (acetylsalicylic acid). The ID50 calculated for this compound was 17.25 micromol/kg, with confidence interval between 13.7 and 21.3 micromol/kg, being about 8 times more potent than the standard drugs. The mixture of two glycoside-flavonoids, identified as astilbin (2) and quercitrin (3), also exhibited good analgesic activity, causing 63% of reduction of abdominal constriction in mice. These results suggest beneficial effect of this plant to treat dolorous processes.