Caracterização farmacológica de efeito antinociceptivo do veneno de Micrurus lemniscatus (coral-verdadeira)

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2012-07-19T20:38:05Z No. of bitstreams: 1 Gisele Graça Leite dos Santos Caracterização farmacológica do efeito....pdf: 994611 bytes, checksum: 83e98f6a9587974ce37d04473a121969 (MD5)Made available in DSpace on 2012-07-19T20:38:05Z (GMT). No. of bitstreams: 1 Gisele Graça Leite dos Santos Caracterização farmacológica do efeito....pdf: 994611 bytes, checksum: 83e98f6a9587974ce37d04473a121969 (MD5) Previous issue date: 2011Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilOs componentes dos venenos das serpentes constituem ferramentas farmacológicas e biotecnológicas relevantes. Recentemente, seu potencial terapêutico tem sido demonstrado; podendo representar a base para o desenvolvimento de medicamentos para o controle da dor. A ausência de dor local, mesmo na presença de edema e inflamação, sugere a presença de componente analgésico no veneno de serpentes do gênero Micrurus. Para investigar essa hipótese, no presente trabalho investigamos a atividade antinociceptiva do veneno de Micrurus lemniscatus em modelos experimentais de dor. Em um teste de triagem para antinocicepção, no teste de contorções abdominais, a administração oral do veneno (19,7 - 1600 μg/kg) produziu efeito antinociceptivo significativo. Confirmando essa atividade, o veneno (1600 μg/kg) inibiu as duas fases do teste de formalina, indicando que um mecanismo central pode estar envolvido na antinocicepção. A participação de um componente central foi confirmada no teste de retirada da cauda no qual o veneno (59 - 1600 μg/kg) produziu efeito antinociceptivo dose-dependente. Neste teste, a dose de 1600 μg/kg produziu efeito antinociceptivo mais potente e duradouro que o efeito da morfina, analgésico considerado padrão ouro. Validando essa antinocicepção, a administração do veneno (1600 μg/kg) não provocou comprometimento motor nos testes de rota-rod e campo aberto. Em outra série de experimentos, os mecanismos envolvidos na atividade antinociceptiva do veneno foram investigados com a utilização de antagonistas farmacológicos de receptores opióides. O efeito antinociceptivo do veneno foi prevenido pela naloxona, antagonista opióide não-seletivo, sugerindo a mediação pelo sistema opióide. Em adição, o pré-tratamento com o antagonista de receptor opióide (CTOP; 1 mg/kg) preveniu completamente o efeito antinociceptivo do veneno. O pré-tratamento com antagonista de receptor k opióide (nor-BNI; 0,5 mg/kg) ou δ opióide (naltrindole; 3 mg/kg) reduziu parcialmente o efeito antinociceptivo desse veneno. Os resultados obtidos demonstram que o veneno de M. lemniscatus apresenta potente efeito antinociceptivo mediado pelo sistema opióide, sobretudo por receptores do tipo . Estudos complementares devem ser realizados para melhor elucidar o mecanismo de ação e o(s) constituinte(s) do veneno envolvido(s) em sua ação antinociceptiva.The components of snake venom are important pharmacological and biotechnology tools. Recently, their therapeutic potential has been demonstrated; which may represent the basis for the development of drugs for pain control. The absence of local pain, even in the presence of edema and inflammation, suggests the presence of an analgesic component in the snake venom of the genus Micrurus. In order to investigate this hypothesis, we studied the antinociceptive activity of Micrurus lemniscatus venom in experimental models of pain. In a screening test for antinociception, the writhing test, oral administration of venom (19,7 - 1600 μg/kg) produced significant antinociceptive effect. Confirming this activity, the venom (1600 μg/kg) inhibited both phases of the formalin test, indicating that a central mechanism may be involved in antinociception. The participation of a central component was confirmed in the tail-flick test, in which the venom (59 - 1600 μg/kg) produced dose-dependent antinociceptive effect. In this test, the dose of 1600 μg/kg produced a more potent and long lasting antinociceptive effect than the one related to morphine, an analgesic considered the gold standard. Corroborating these results, administration of venom (1600 μg/kg) did not cause motor impairment in the rota-rod and open field tests. In another series of experiments, the mechanisms involved in the venom antinociceptive activity were investigated through the use of pharmacological antagonists of opioid receptors. The venom antinociceptive effect was prevented by naloxone, a non-selective opioid receptor antagonist, suggesting mediation by the opioid system. In addition, pretreatment with a opioid receptor antagonist (CTOP, 1 mg/kg) completely prevented the venom antinociceptive effect. On the other hand, pretreatment with k opioid receptor antagonist (nor-BNI, 0,5 mg/kg) or δ opioid receptor antagonist (naltrindole; 3 mg/kg) partially reduced the venom antinociception. The present results show that the venom of M. lemniscatus has potent antinociceptive effect mediated by the opioid system, especially by the receptor . Further studies should be conducted to better elucidate the mechanism of action of this venom and its component(s), which are involved in its antinociception

Antinociceptive properties of Micrurus lemniscatus venom

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2013-11-14T18:05:41Z No. of bitstreams: 1 Gisele Graça Leite dos Santos Antinociceptive....pdf: 619941 bytes, checksum: b5a51fdefe0012c7691d360620260921 (MD5)Made available in DSpace on 2013-11-14T18:05:41Z (GMT). No. of bitstreams: 1 Gisele Graça Leite dos Santos Antinociceptive....pdf: 619941 bytes, checksum: b5a51fdefe0012c7691d360620260921 (MD5) Previous issue date: 2012Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Ciências da Saúde. Salvador, BA, Brasil / Universidade do Estado da Bahia. Departamento de Ciências da Vida. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, BrasilThe therapeutic potential of snake venoms for pain control has been previously demonstrated. In the present study, the antinociceptive effects of Micrurus lemniscatus venom (MlV) were investigated in experimental models of pain. The antinociceptive activity of MIV was evaluated using the writhing, formalin, and tail flick tests. Mice motor performance was assessed in the rota rod and open field tests. In a screening test for new antinociceptive substances – the writhing test – oral administration of MlV (19.7–1600 mg/ kg) produced significant antinociceptive effect. The venom (1600 mg/kg) also inhibited both phases of the formalin test, confirming the antinociceptive activity. The administration of MlV (1600 mg/kg) did not cause motor impairment in the rota rod and open field tests, which excluded possible non-specific muscle relaxant or sedative effects of the venom. The MIV (177–1600 mg/kg) also increases the tail flick latency response, indicating a central antinociceptive effect for the venom. In this test, the MlV-induced antinociceptive effect was long-lasting and higher than that of morphine, an analgesic considered the gold standard. In another set of experiments, the mechanisms involved in the venom-induced antinociception were investigated through the use of pharmacological antagonists. The MlV (1600 mg/kg) antinociceptive effect was prevented by naloxone (5 mg/kg), a nonselective opioid receptor antagonist, suggesting that this effect is mediated by activation of opioid receptors. In addition, the pre-treatment with the m-opioid receptor antagonist CTOP (1 mg/kg) blocked the venom antinociceptive effect, while the k-opioid receptor antagonist nor-BNI (0.5 mg/kg) or the d-opioid receptor antagonist naltrindole (3 mg/kg) only partially reduced the venom-induced antinociception. The present study demonstrates, for the first time, that oral administration of M. lemniscatus venom, at doses that did not induce any motor performance alteration, produced potent and long-lasting antinociceptive effect mediated by activation of opioid receptors

Antinociceptive properties of physalins from Physalis angulata.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-03-11T19:17:13Z No. of bitstreams: 1 Lima MS Antinocicptive....pdf: 992187 bytes, checksum: 7a499c23ff111fc40f8a4d978d9113e0 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-03-11T19:17:22Z (GMT) No. of bitstreams: 1 Lima MS Antinocicptive....pdf: 992187 bytes, checksum: 7a499c23ff111fc40f8a4d978d9113e0 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-03-16T17:10:13Z (GMT) No. of bitstreams: 1 Lima MS Antinocicptive....pdf: 992187 bytes, checksum: 7a499c23ff111fc40f8a4d978d9113e0 (MD5)Made available in DSpace on 2015-03-16T17:10:14Z (GMT). No. of bitstreams: 1 Lima MS Antinocicptive....pdf: 992187 bytes, checksum: 7a499c23ff111fc40f8a4d978d9113e0 (MD5) Previous issue date: 2014Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. FarManguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. FarManguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil /Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilPain is the most common reason a patient sees a physician. Nevertheless, the use of typical painkillers is not completely effective in controlling all pain syndromes; therefore further attempts have been made to develop improved analgesic drugs. The present study was undertaken to evaluate the antinociceptive properties of physalins B (1), D (2), F (3), and G (4) isolated from Physalis angulata in inflammatory and centrally mediated pain tests in mice. Systemic pretreatment with 1-4 produced dose-related antinociceptive effects on the writhing and formalin tests, traditional screening tools for the assessment of analgesic drugs. On the other hand, only 3 inhibited inflammatory parameters such as hyperalgesia, edema, and local production of TNF-α following induction with complete Freund's adjuvant. Treatment with 1, 3, and 4 produced an antinociceptive effect on the tail flick test, suggesting a centrally mediated antinociception. Reinforcing this idea, 2-4 enhanced the mice latency reaction time during the hot plate test. Mice treated with physalins did not demonstrate motor performance alterations. These results suggest that 1-4 present antinociceptive properties associated with central, but not anti-inflammatory, events and indicate a new pharmacological property of physalins

Anti-inflammatory properties of rose oxide

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2013-11-13T16:54:35Z No. of bitstreams: 1 Nonato FR Anti-inflammatory....pdf: 514931 bytes, checksum: 14769cc91d175162ca0896db2847d9cc (MD5)Made available in DSpace on 2013-11-13T16:54:35Z (GMT). No. of bitstreams: 1 Nonato FR Anti-inflammatory....pdf: 514931 bytes, checksum: 14769cc91d175162ca0896db2847d9cc (MD5) Previous issue date: 2012Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal de Sergipe. Departamento de Fisiologia. São Cristóvão, Sergipe, BrasilUniversidade Federal da Bahia. Faculdade de Farmácia. Salvador, Bahia, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal de Sergipe. Departamento de Fisiologia. São Cristóvão, Sergipe, BrasilUniversidade Federal de Sergipe. Departamento de Fisiologia. São Cristóvão, Sergipe, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, Bahia, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, Bahia, BrasilRose-oxide is a fragrance found in roses and rose oil. There are no reports about the pharmacological activity of this molecule. The present study was undertaken to evaluate whether rose-oxide (RO) has anti-inflammatory properties and to investigate possible mechanisms involved with its effects. The anti-inflammatory activity of RO was first suggested by the formalin test in mice, an inflammatory pain model, because intraperitoneal (i.p.) administration of RO (50 and 100 mg/kg) inhibited only the late phase of this test. To further investigate the anti-inflammatory properties of RO, the complete Freund's adjuvant (CFA)- and carrageenan-induced paw inflammation models were used. Pre-treatment with RO (50 and 100 mg/kg) significantly reduced paw edema at 4, 6 and 24 h after the CFA injection. In addition, RO (100 mg/kg) reduced the IL-1β, but not TNF-α, local production induced by CFA. Administration of RO (25–100 mg/kg) decreased the paw edema induced by carrageenan in rats, which was more evident at 3 and 4 h after induction. In addition, neutrophil migration to the hind paw was measured by MPO assay after the carrageenan injection. The MPO activity was significantly inhibited by RO at 25–100 mg/kg, 4 h after stimulus. In another experimental set, administration of RO (25–100 mg/kg) significantly reduced the leukocyte migration in the carrageenan-induced peritonitis model in mice. The results described here are the first report of pharmacological properties of RO and strongly suggest that RO possesses anti-inflammatory activity related to its ability to inhibit the IL-1β production and the leukocyte migration

Antinociceptive compounds and LC-DAD-ESIMSn profile from Dictyoloma vandellianum leaves.

Limonoids, quinolone alkaloids and chromones have been reported as constituents of Dictyoloma vandellianum Adr. Juss. (Rutaceae). Although those compounds are known for their biological activities, only the anti-inflammatory activity of chromones isolated from the underground parts has been evaluated. There are no studies of the pharmacological properties of the aerial parts of D. vandellianum. The present study was carried out to determine the phytochemical profile and antinociceptive activity of the methanol extract, fractions and isolated compounds of leaves of D. vandellianum. The phytochemical profile was performed by HLPC-DAD-ESIMSn and pure substances obtained were characterized by MS and NMR spectroscopy. The antinociceptive activity was assessed using the formalin assay in mice, and the motor function in the rotarod test. ME and all the fractions obtained from ME produced antinociceptive effects. Among them, the ethyl ether fraction was the most active. Data from HPLC-DAD-ESIMSn showed that the ethyl ether fraction presented 42 compounds. The major compounds isolated from this fraction-gallic acid, methyl gallate and 1,2,6-tri-O-galloyl-β-d-glucopyranose-were tested and produced antinociceptive effects. Gallic acid, methyl gallate and 1,2,6-tri-O-galloyl-β-d-glucopyranose at antinociceptive doses did not affect the motor performance in mice in the rotarod test. This work is the first report of the occurrence of gallotanins in D. vandellianum. In addition, the pharmacological study showed that D. vandellianum leaves present antinociceptive activity, probably induced by gallic acid, methyl gallate and 1,2,6-tri-O-galloyl-β-d-glucopyranose