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1.
Toxicol Appl Pharmacol ; 369: 30-38, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30763598

RESUMO

Despite all the development of modern medicine, around 100 compounds derived from natural products were undergoing clinical trials only at the end of 2013. Among these natural substances in clinical trials, we found the resveratrol (RES), a pharmacological multi-target drug. RES analgesic properties have been demonstrated, although the bases of these mechanisms have not been fully elucidated. The aim of this study was to evaluate the involvement of opioid and cannabinoid systems in RES-induced peripheral antinociception. Paw withdrawal method was used and hyperalgesia was induced by carrageenan (200 µg/paw). All drugs were given by intraplantar injection in male Swiss mice (n = 5). RES (100 µg/paw) administered in the right hind paw induced local antinociception that was antagonized by naloxone, non-selective opioid receptor antagonist, and clocinnamox, µOR selective antagonist. Naltrindole and nor-binaltorfimine, selective antagonists for δOR and kOR, respectively, did not reverse RES-induced peripheral antinociception. CB1R antagonist AM251, but not CB2R antagonist AM630, antagonized RES-induced peripheral antinociception. Peripheral antinociception of RES intermediate-dose (50 µg/paw) was increased by: (i) bestatin, inhibitor of endogenous opioid degradation involved-enzymes; (ii) MAFP, inhibitor of anandamide amidase; (iii) JZL184, inhibitor of 2-arachidonoylglycerol degradation involved-enzyme; (iv) VDM11, endocannabinoid reuptake inhibitor. Acute and peripheral administration of RES failed to affect the amount of µOR, CB1R and CB2R. Experimental data suggest that RES induces peripheral antinociception through µOR and CB1R activation by endogenous opioid and endocannabinoid releasing.


Assuntos
Analgésicos/farmacologia , Endocanabinoides/metabolismo , Hiperalgesia/prevenção & controle , Dor Nociceptiva/prevenção & controle , Peptídeos Opioides/metabolismo , Receptor CB1 de Canabinoide/agonistas , Receptores Opioides mu/agonistas , Resveratrol/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Antagonistas de Receptores de Canabinoides/farmacologia , Carragenina , Modelos Animais de Doenças , Hiperalgesia/induzido quimicamente , Hiperalgesia/metabolismo , Hiperalgesia/psicologia , Masculino , Camundongos , Antagonistas de Entorpecentes/farmacologia , Dor Nociceptiva/induzido quimicamente , Dor Nociceptiva/metabolismo , Dor Nociceptiva/psicologia , Receptor CB1 de Canabinoide/metabolismo , Receptores Opioides mu/metabolismo , Transdução de Sinais
2.
Planta Med ; 83(3-04): 261-267, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27574895

RESUMO

Peltatoside is a natural compound isolated from leaves of Annona crassiflora Mart., a plant widely used in folk medicine. This substance is an analogue of quercetin, a flavonoid extensively studied because of its diverse biological activities, including analgesic effects. Besides, a previous study suggested, by computer structure analyses, a possible quercetin-CB1 cannabinoid receptor interaction. Thus, the aim of this work was to assess the antinociceptive effect of peltatoside and analyze the cannabinoid system involvement in this action. The mouse paw pressure test was used and hyperalgesia was induced by intraplantar injection of carrageenan (200 µg/paw). All used drugs were administered by intraplantar administration in Swiss male mice (n = 6). Peltatoside (100 µg/paw) elicited a local inhibition of hyperalgesia. The peripheral antinociceptive action of peltatoside was antagonized by the CB1 cannabinoid antagonist AM251 (160 µg/paw), but not by CB2 cannabinoid antagonist AM630 (100 µg/paw). In order to assess the role of endocannabinoids in this peripheral antinociceptive effect, we used (i) [5Z,8Z,11Z,14Z]-5,8,11,14-eicosatetraenyl-methyl ester phosphonofluoridic acid, an inhibitor of anandamide amidase; (ii) JZL184, an inhibitor for monoacylglycerol lipase, the primary enzyme responsible for degrading the endocannabinoid 2-arachidonoylglycerol; and (iii) VDM11, an endocannabinoid reuptake inhibitor. MAFP, JZL184, and VDM11 did not induce antinociception, respectively, at the doses 0.5, 3.8, and 2.5 µg/paw, however, these three drugs were able to potentiate the peripheral antinociceptive effect of peltatoside at an intermediary dose (50 µg/paw). Our results suggest that this natural substance is capable of inducing analgesia through the activation of peripheral CB1 receptors, involving endocannabinoids in this process.


Assuntos
Analgésicos/farmacologia , Canabinoides/metabolismo , Glicosídeos/farmacologia , Quercetina/análogos & derivados , Amidoidrolases/metabolismo , Analgésicos/química , Analgésicos/isolamento & purificação , Animais , Annona/química , Benzodioxóis/administração & dosagem , Benzodioxóis/farmacologia , Antagonistas de Receptores de Canabinoides/farmacologia , Carragenina/antagonistas & inibidores , Carragenina/farmacologia , Relação Dose-Resposta a Droga , Endocanabinoides/metabolismo , Glicosídeos/antagonistas & inibidores , Glicosídeos/química , Glicosídeos/isolamento & purificação , Hiperalgesia/tratamento farmacológico , Masculino , Camundongos , Monoacilglicerol Lipases/efeitos dos fármacos , Medição da Dor/efeitos dos fármacos , Piperidinas/administração & dosagem , Piperidinas/farmacologia , Extratos Vegetais/farmacologia , Pirazóis/farmacologia , Quercetina/antagonistas & inibidores , Quercetina/química , Quercetina/isolamento & purificação , Quercetina/farmacologia , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/antagonistas & inibidores , Receptor CB2 de Canabinoide/metabolismo
3.
Pharmacol Rep ; 68(6): 1095-1101, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27573715

RESUMO

INTRODUCTION: This study was conducted with the aim of evaluating whether electroacupuncture (EA) at acupoint St36 could produce antinociception through the activation of an endocannabinoid mechanism. METHODS: Male Wistar rats were divided into experimental groups. Heat was applied to the faces of rats, and the latency to withdraw the face was measured. Furthermore, the influence of electrical stimulation (100HzP) of acupoint St36, at a 0.5mA intensity, was investigated in the facial withdrawal threshold. RESULTS: The EA produced antinociception, which lasted for 180min. This effect was antagonized by the pre-injection of AM 251, a CB1 cannabinoid receptor antagonist, but not by AM 630, a CB2 cannabinoid receptor antagonist. Additionally, pretreatment with an endocannabinoid metabolizing enzyme inhibitor (MAFP) and an anandamide reuptake inhibitor (VDM11) prolonged and intensified the antinociceptive effect produced by EA. CONCLUSION: This study demonstrated for the first time that the CB1 cannabinoid receptor participates in the antinociceptive effect induced by EA.


Assuntos
Pontos de Acupuntura , Eletroacupuntura/métodos , Endocanabinoides/metabolismo , Dor Facial/metabolismo , Dor Facial/terapia , Medição da Dor/métodos , Animais , Agonistas de Receptores de Canabinoides/farmacologia , Agonistas de Receptores de Canabinoides/uso terapêutico , Antagonistas de Receptores de Canabinoides/farmacologia , Antagonistas de Receptores de Canabinoides/uso terapêutico , Relação Dose-Resposta a Droga , Indóis/farmacologia , Indóis/uso terapêutico , Masculino , Medição da Dor/efeitos dos fármacos , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Ratos , Ratos Wistar
4.
Planta Med ; 82(1-2): 106-12, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26460671

RESUMO

Cafestol and kahweol are diterpenes found only in the non-saponified lipid fraction of coffee. They are released during boiling and retained in the filtration process. Previous studies have shown peripheral antinociception induced by endogenous opioid peptides released by these diterpenes. Considering that the activation of the opioid system leads to a noradrenaline release, the aim of this study was to verify the participation of the noradrenergic system in the peripheral antinociception induced by cafestol and kahweol. Hyperalgesia was induced by an intraplantar injection of prostaglandin E2 (2 µg). Cafestol or kahweol (80 µg/paw) were administered locally into the right hindpaw alone, and after the agents α 2-adrenoceptor antagonist yohimbine (5, 10 and 20 µg/paw), α 2 A-adrenoceptor antagonist BRL 44 408 (40 µg/paw), α 2B-adrenoceptor antagonist imiloxan (40 µg/paw), α 2 C-adrenoceptor antagonist rauwolscine (10, 15 and 20 µg/paw), α 2D-adrenoceptor antagonist RX 821 002 (40 µg/paw), α 1-adrenoceptor antagonist prazosin (0.5, 1 and 2 µg/paw), or ß-adrenoceptor antagonist propranolol (150, 300 and 600 ng/paw), respectively. Noradrenaline reuptake inhibitor reboxetine (30 µg/paw) was administered prior to cafestol or kahweol low dose (40 µg/paw) and guanetidine 3 days prior to the experiment (30 mg/kg, once a day), depleting the noradrenaline storage. Intraplantar injection of cafestol or kahweol (80 µg/paw) induced a peripheral antinociception against hyperalgesia induced by PGE2. This effect was reversed by intraplantar injections of yohimbine, rauwolscine, prazosin and propranolol. Reboxetine injection intensified the antinociceptive effect of cafestol or kahweol low-dose, and guanethidine reversed almost 70 % of the cafestol or kahweol-induced peripheral antinociception. This study gives evidence that the noradrenergic system participates in cafestol and kahweol-induced peripheral antinociception with the release of endogenous noradrenaline.


Assuntos
Analgésicos/farmacologia , Café/química , Diterpenos/farmacologia , Receptores Adrenérgicos/efeitos dos fármacos , Animais , Diterpenos/química , Masculino , Estrutura Molecular , Ratos , Ratos Wistar , Receptores Adrenérgicos/metabolismo , Receptores Adrenérgicos alfa 2/efeitos dos fármacos , Receptores Adrenérgicos alfa 2/metabolismo
5.
J Nat Med ; 69(4): 487-93, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25894075

RESUMO

We aimed to study the antinociceptive effects of myricetin 3-O-ß-galactoside (Mi), a substance isolated from the hydroalcoholic extract of Davilla elliptica. This study examined male Swiss mice, inducible nitric oxide synthase C57B16/J knockout mice (iNOS(-/-)), and their corresponding wild type (WT). Formalin and tail-flick tests were used to evaluate the nociceptive threshold, and the carrageenan-induced paw edema test was used as a model for inflammation. The following drugs were administered to investigate the involvement of the nitrergic and opioidergic systems: L-NAME, a nonspecific nitric oxide synthase (NOS) inhibitor; L-arginine (L-Arg), a precursor for the synthesis of nitric oxide (NO); D-arginine (D-Arg), an inactive isomer for the synthesis of NO; aminoguanidine (Am), an inducible nitric oxide synthase (iNOS) inhibitor; and naloxone, a nonselective antagonist of opioid receptors. The results showed that oral pretreatment with Mi caused a dose-dependent inhibition of the inflammatory phase of the formalin test and did not alter motor performance. Intraperitoneal injection of L-NAME caused a reduction in the licking time during the second phase of the formalin test. The administration of L-Arg (but not D-Arg) reversed the antinociceptive effect of L-NAME. Furthermore, pre-administration of aminoguanidine potentiated the antinociceptive effect. Mi did not cause an antinociceptive effect in iNOS knockouts and led to a reduction in the nitrite concentration in the paws of mice. Carrageenan-induced paw edema was reduced in Swiss mice and WT mice when compared to iNOS(-/-) mice. Pre-administration of naloxone (NLX) did not reverse the antinociceptive effect of Mi, excluding the opioidergic system as a mediator of the antinociceptive effect. Thus, the results suggest that the antinociceptive and anti-inflammatory effects of myricetin 3-O-ß-galactoside are related to peripheral inhibition of nitric oxide synthesis, mainly iNOS.


Assuntos
Analgésicos/metabolismo , Anti-Inflamatórios/metabolismo , Edema/tratamento farmacológico , Galactosídeos/química , Óxido Nítrico/química , Plantas Medicinais/química , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
6.
Planta Med ; 80(17): 1615-21, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25338214

RESUMO

Plants belonging to the genus Maytenus are routinely used in folk medicine for the treatment of pain diseases. Our previous phytochemical study of the roots of Maytenus imbricata resulted in the isolation and characterization of tingenone, a pentacyclic triterpene. Natural triterpenoids are of growing interest because they have several biological activities, including analgesic properties. The present study assessed the involvement of the opiodergic pathway in the tingenone-induced antinociceptive effect against hyperalgesia induced by prostaglandin E2 (2 µg) in the peripheral pathway. We evaluated the effect of several antagonists to opioid receptors using the mouse paw pressure test. Tingenone administered into the right hind paw induced a local antinociceptive effect that was antagonized by naloxone, a nonselective antagonist to opioid receptors. Clocinnamox, naltrindole, and nor-binaltorphimine are selective antagonists to µ, δ, and κ receptors, respectively, which reverted the peripheral antinociception induced by tingenone. Bestatine acts as an inhibitor of aminopeptidase, an enzyme that degrades endogenous opioid peptides, and was shown to intensify the antinociceptive effect of tingenone. The results suggest that the opioidergic system participates in the peripheral antinociception induced by tingenone.


Assuntos
Analgésicos Opioides/farmacologia , Analgésicos/farmacologia , Maytenus/química , Triterpenos/farmacologia , Analgésicos/efeitos adversos , Analgésicos/isolamento & purificação , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/isolamento & purificação , Animais , Hiperalgesia/tratamento farmacológico , Masculino , Camundongos , Triterpenos/efeitos adversos , Triterpenos/isolamento & purificação
7.
J Ethnopharmacol ; 151(1): 722-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24309496

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Pyrostegia venusta is used in traditional Brazilian medicine as a general tonic to treat any inflammatory disease. Several studies have demonstrated that medicinal plants constitute a therapeutic approach for the treatment of obesity-related metabolic and inflammatory disarrangement. Accordingly, we investigated the effects of hydroethanolic extract of Pyrostegia venusta flowers (PvHE) supplementation for the treatment of inflammatory and metabolic dysfunction induced by high-refined-carbohydrate (HC) diet. MATERIAL AND METHODS: The BALB/c mice were fed chow or HC diet for 8 weeks. Part of these animals was fed with HC diet supplemented with PvHE on the 9th week until the 12th week. At the end of the dietary intervention, animals were sacrificed. RESULTS: We observed that PvHE decreased adiposity and adipocyte area; improved glucose intolerance; reduced serum triacylglycerol levels and systemic inflammatory cells; and also reduced some inflammatory mediators levels in adipose tissue and liver. CONCLUSION: The results showed that PvHE has beneficial effects and may treat inflammatory and metabolic dysfunction induced by HC diet, that are associated to a negative modulation of the inflammatory process at systemic and local levels.


Assuntos
Bignoniaceae/química , Carboidratos da Dieta/efeitos adversos , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Carboidratos da Dieta/administração & dosagem , Feminino , Teste de Tolerância a Glucose , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/química
8.
Rev. odontol. UNESP ; 28(1): 161-5, jan.-jun. 1999. ilus
Artigo em Português | LILACS, BBO - Odontologia | ID: lil-271345

RESUMO

Neste trabalho testamos os efeitos antiinflamatórios do extrato hidroalcoólico de folhas de Ipomoea batatas. O modelo experimental de inflamaçäo utilizado foi de edema de pata de ratos induzido pelo composto 48/80. Apesar de ser comumente utilizada na medicina popular, esse tipo de extrato näo apresentou nenhum efeito antiinflamatório no modelo experimental utilizado


Assuntos
Animais , Ratos , Homeopatia , Medicina Tradicional , Solanaceae/uso terapêutico
9.
Rev. odontol. UNESP ; 26(2): 297-305, jul.-dez. 1997. ilus
Artigo em Português | LILACS, BBO - Odontologia | ID: lil-224069

RESUMO

O presente trabalho teve como finalidade analisar o efeito de um inibidor do óxido nítrico no rim de ratos normais e diabéticos. Observamos que L-NG-nitro arginina metil éster (L-NAME), além de causar hipertensäo arterial, näo teve nenhum efeito na morfologia renal e, também näo atenuou a diabetes pela inibiçäo da produçäo do NO. O conhecimento sobre a produçäo de NO por ilhotas de Langerhans ainda precisa ser melhor estudado, porém este é um modelo eficaz para estudo de hipertensäo


Assuntos
Animais , Ratos , Glicosúria Renal , Óxido Nítrico , NG-Nitroarginina Metil Éster
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