Peripheral antinociceptive action of mangiferin in mouse models of experimental pain: Role of endogenous opioids, KATP-channels and adenosine

AbstractThis study aimed to assess the possible systemic antinociceptive activity of mangiferin and to clarify the underlying mechanism, using the acute models of chemical (acetic acid, formalin, and capsaicin) and thermal (hot-plate and tail-flick) nociception in mice. Mangiferin at oral doses of 10 to 100mg/kg evidenced significant antinociception against chemogenic pain in the test models of acetic acid-induced visceral pain and in formalin- and capsaicin-induced neuro-inflammatory pain, in a naloxone-sensitive manner, suggesting the participation of endogenous opiates in its mechanism. In capsaicin test, the antinociceptive effect of mangiferin (30mg/kg) was not modified by respective competitive and non-competitive transient receptor potential vanilloid 1 (TRPV1) antagonists, capsazepine and ruthenium red, or by pretreatment with l-NAME, a non-selective nitric oxide synthase inhibitor, or by ODQ, an inhibitor of soluble guanylyl cyclase. However, mangiferin effect was significantly reversed by glibenclamide, a blocker of KATP channels and in animals pretreated with 8-phenyltheophylline, an adenosine receptor antagonist. Mangiferin failed to modify the thermal nociception in hot-plate and tail-flick test models, suggesting that its analgesic effect is only peripheral but not central. The orally administered mangiferin (10–100mg/kg) was well tolerated and did not impair the ambulation or the motor coordination of mice in respective open-field and rota-rod tests, indicating that the observed antinociception was unrelated to sedation or motor abnormality. The findings of this study suggest that mangiferin has a peripheral antinociceptive action through mechanisms that involve endogenous opioids, KATP-channels and adenosine receptors

Attenuation of capsaicin-induced acute and visceral nociceptive pain by α- and β-amyrin, a triterpene mixture isolated from Protium heptaphyllum resin

Abstract The triterpene mixture, a-and h-amyrin, isolated from Protium heptaphyllum resin was evaluated on capsaicinevoked nociception in mice. Orally administered a-and h-amyrin (3 to 100 mg/kg) significantly suppressed the nociceptive behaviors-evoked by either subplantar (1.6 Ag) or intracolonic (149 Ag) application of capsaicin. The antinociception produced by a-and h-amyrin against subplantar capsaicin-induced paw-licking behavior was neither potentiated nor attenuated by ruthenium red (1.5 mg/kg, s.c.), a non-specific antagonist of vanilloid receptor (TRPV1), but was greatly abolished in animals pretreated with naloxone (2 mg/kg, s.c.), suggesting an opioid mechanism. However, participation of a 2 -adrenoceptor involvement was unlikely since yohimbine (2 mg/ kg, i.p.) pretreatment failed to block the antinociceptive effect of a-and h-amyrin in the experimental model of visceral nociception evoked by intracolonic capsaicin. The triterpene mixture (3 to 30 mg/kg, p.o.) neither altered significantly the pentobarbital sleeping time, nor impaired the ambulation or motor coordination in open-field and rota-rod tests, respectively, indicating the absence of sedative or motor abnormality that could account for its antinociception. Nevertheless, a-and h-amyrin could significantly block the capsaicin (10 mg/kg, s.c.)-induce

Gastroprotective effect of Byrsonima sericea DC leaf extract against ethanol-induced gastric injury and its possible mechanisms of action

Byrsonima sericea leaves are extensively used in folk medicine in Brazil against gastric disorders. This study investigated the chemical constituents of B. sericea leaf ethanolic extract (BSLE) and its potential gastroprotective activity, with its possible mechanism of the action using ethanol to induce gastric mucosal damage in mice. The phytochemical analysis was carried out to identify the active constituents present in the extract, and the HPLC analysis was performed for the identification of flavonoids. BSLE at oral doses of 125, 250 and 500 mg/kg markedly attenuated the ethanol-evoked gastric lesions by 53.2, 84.9 and 87.6 %, respectively. The BSLE (250 mg/kg) prevented the depletion of gastric mucus and gastric mucosal nonproteic-sulfhydryl groups, SOD and CAT, as well as the increase in the MDA content promoted by absolute ethanol. Moreover, the effect of BSLE against ethanol damage was found to be significantly reduced in mice pretreated with Capsazepine (i.p.), L-NAME (i.p.) or glibenclamide (i.p.), the respective blockers/inhibitors of TRPV1, NO synthase and K+ATP channel. The phytochemical investigation on BSLE revealed the presence of flavonoids rutin, isoquercitrin, kaempferol 3-O-rutinoside and quercetin, which are compounds well known for their antioxidant and gastroprotective properties. These results suggest that BSLE affords gastroprotection through multiple mechanisms, which may be helpful in the treatment of pathologies associated with gastric dysfunctions.<br>Folhas de Byrsonima sericea são amplamente utilizadas na medicina popular no Brasil no tratamento de distúrbios gástricos. Este estudo investigou os constituintes químicos do extrato etanólico das folhas de B. sericea (BSLE) e sua atividade gastroprotetora com seus possíveis mecanismos de ação utilizando o modelo de lesão gástrica induzida por etanol em camundongos. A análise fitoquímica foi realizada para identificar os componentes ativos presentes no extrato e análise por HPLC foi realizada para a identificação de flavonóides. A administração de BSLE (v.o.) nas doses de 125, 250, 500 mg/kg, v.o. atenuou significativamente as lesões gástricas induzidas por etanol em 53,2, 84,9 e 87,6% respectivamente. BSLE (250 mg/kg) preveniu a depleção do muco gástrico, de grupamentos sulfidrílicos não-protéicos (GSH), das atividades da SOD e da CAT assim como o aumento de malonaldeído promovido pelo etanol. Além disso, o efeito gastroprotetor do BSLE foi significantemente reduzido pelos pré-tratamentos com capsazepina (i.p.), L-NAME (i.p.) ou glibenclamida (i.p.), respectivamente bloqueadores/inibidores de receptores TRPV1, NO sintase e canais de K+ATP. A investigação fitoquímica revelou a presença de flavonoides como rutina, isoquercitrina, 3-O-rutinosideo-canferol e quercetina que são conhecidas por suas propriedades antioxidantes e gastropotetoras. O estudo demonstrou que BSLE proporciona ação gastroprotetora através de vários mecanismos que podem ser úteis no tratamento de patologias associadas a disfunções gástricas

Anti-inflammatory, antinociceptive, and antipyretic effects of methanol extract of Cariniana rubra stem bark in animal models

Cariniana rubra Miers (Lecythidaceae), popularly known as "jequitibá-vermelho'', is a large Brazilian tree whose bark is used in infusion and decoction for the treatment of inflammatory conditions. This study aims to assess the anti-inflammatory, antinociceptive, and antipyretic effects of Cariniana rubra methanolic stem bark extract (EM Cr) using experimental animals. Anti-inflammatory activity of EM Cr was tested on carrageenan and dextran-induced rat paw edema, carrageenan-induced pleurisy in rats and acetic acid-increase vascular permeability in mice. Antinociceptive and antipyretic activities were evaluated using acetic acid-induced writhing, formalin and hot-plate tests in mice, as well as brewer's yeast-induced pyrexia in rats. The extract inhibitied carrageenan and dextran-induced edema, reduced exudate volume and leukocyte migration on the carrageenan-induced pleurisy and on the vascular permeability increase induced by acetic acid. The EM Cr inhibited nociception on the acetic acid-induced writhing and in the second phase of formalin test, and decreased rectal temperature. It was, however, inactive against thermal nociception.Phytochemical analysis with EM Cr showed the occurrence of saponins, triterpenes, sterols and phenolic compounds. Phytosterols (&#946;-sitosterol, stigmasterol), pentacyclic triterpenes (&#945;- and &#946;-amyrin as a mixture), arjunolic acid, a phytosterol glycoside (sitosterol 3-O-&#946;-D-glucopyranoside), and triterpenoid saponins (28-&#946;-glucopyranosyl-23-O-acetyl arjunolic acid; 3-O-&#946;-glucopyranosyl arjunolic acid and 28-O-[&#945;-L-Rhamnopyranosyl-(1&#8594;2)-&#946;-glucopyranosyl]-23- O-acetyl arjunolic acid) were the main identified compounds. It can be presumed that EM Cr caused their effects by inhibiting the liberation and/or action of different inflammatory mediators. These findings support the traditional use of Cariniana rubra preparations to treat inflammation.<br>Cariniana rubra Miers (Lecythidaceae), popularmente conhecido como "jequitibá-vermelho'', é uma árvore brasileira de grande porte, cuja casca é utilizada nas formas de infusão e decocção para o tratamento de condições inflamatórias. Os efeitos antiinflamatório, antinociceptivo e antipirético do extrato metanólico da casca do caule de Cariniana rubra (EM Cr) foram avaliados em animais experimentais. A atividade antiinflamatória do EM Cr foi testada nos modelos de edema depata induzido por carragenina e dextrana em ratos, pleurisia induzida por carragenina em ratos e permeabilidade vascular aumentada por ácido acético em ratos. As atividades antinociceptiva e antipirética foram avaliadas utilizando os modelos de nocicepções induzidos por ácido acético e formalina, placa quente em camundongos e de pirexia, pela injeção de levedura de cerveja em ratos. O extrato inibiu o edema induzido porcarragenina e dextrana, reduziu o volume de exsudato e a migração de leucócitos na pleurisia induzida por carragenina eo aumento da permeabilidade vascular induzida por ácidoacético. O EM Cr inibiu a nocicepção nas contorções induzidas por ácido acético e na segunda fase do teste de formalina e diminuiu a temperatura retal. No entanto, foi inefetivo no teste da placa quente. A análise química por via úmida deu resultados positivos para saponinas, triterpenos, esteroides e compostos fenólicos. Fitosteróis e triterpenóides pentacíclicos (&#946;-sitosterol, estigmasterol, &#945; and &#946;-amirinas em mistura e ácido arjunólico) e as saponinas triterpenoidais: 3-O-&#946;-D-glucopiranosideo de sitosterol; ácido arjunólico 28-&#946;-glucopiranosila-23-O-acetila; ácido arjunólico 3-O-&#946;-glucopiranosila e ácido arjunólico 28-O-[&#945;-L-rhamnopiranosil-(1&#8594;2)-&#946;-D-glucopiranosila]-23-O-acetila. Pode-se presumir que os efeitos do EM Cr foram causados pela inibição da liberação e/ou ação de diversos mediadores inflamatórios. Estes resultados validam o uso tradicional das preparações caseiras de Cariniana rubra para tratar a inflamação

1,8-cineole protects against liver failure in an in-vivo murine model of endotoxemic shock

Freitas, Luiz Antônio Rodrigues de “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”.Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-08-11T17:34:03Z No. of bitstreams: 1 Santos FA 1,8-cineole protects....pdf: 313163 bytes, checksum: 4b7a5a588d0cf5796c69e4c36104b90e (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-08-11T17:51:35Z (GMT) No. of bitstreams: 1 Santos FA 1,8-cineole protects....pdf: 313163 bytes, checksum: 4b7a5a588d0cf5796c69e4c36104b90e (MD5)Made available in DSpace on 2017-08-11T17:51:35Z (GMT). No. of bitstreams: 1 Santos FA 1,8-cineole protects....pdf: 313163 bytes, checksum: 4b7a5a588d0cf5796c69e4c36104b90e (MD5) Previous issue date: 2001Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, 300870/98-1).Federal University of Ceará. Department of Physiology and Pharmacology. Fortaleza, CE, BrasilFederal University of Ceará. Department of Physiology and Pharmacology. Fortaleza, CE, BrasilFederal University of Ceará. Department of Physiology and Pharmacology. Fortaleza, CE, BrasilFederal University of Ceará. Department of Physiology and Pharmacology. Fortaleza, CE, BrasilFederal University of Ceará. Department of Pathology and Legal Medicine. Fortaleza,Federal University of Ceará. Department of Pathology and Legal Medicine. Fortaleza,Fundação Oswaldo Cruz. Laboratório de Patologia e Biologia Celular. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Laboratório de Patologia e Biologia Celular. Rio de Janeiro, RJ, BrasilThe effects of 1,8-cineole on D-galactosamine/lipopolysaccharide (GalN/LPS)-induced shock model of liver injury was investigated in mice. The co-administration of GalN (700 mg kg−1, i.p.) and LPS (5 lgkg−1, i.p.) greatly elevated serum concentrations of tumour necrosis factor-a (TNFa), alanine aminotransferase and aspartate aminotransferase, and induced massive hepatic necrosis and lethality in 100% of control mice. Pretreatment with 1,8-cineole (400 mg kg−1, p.o.) and dexamethasone (1 mgkg−1, s.c.), 60 min before GalN/LPS, offered complete protection (100%) against the lethal shock and acute elevation in serum TNF-a and serum transaminases. Hepatic necrosis induced by GalN/LPS was also greatly reduced by both 1,8-cineole and dexamethasone treatment. The results indicate that 1,8-cineole protects mice against GalN/LPSinduced liver injury through the inhibition of TNF-a production, and suggest that 1,8-cineole may be a promising agent to combat septic-shock-associated pathologies