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BACKGROUND: The development of analgesic and anti-inflammatory drugs plays a crucial role in modern medicine, aiming to alleviate pain and reduce inflammation in patients. Opioids and nonsteroidal anti-inflammatory drugs are groups of drugs conventionally used to treat pain and inflammation, but a wide range of adverse effects and ineffectiveness in some pathological conditions leads us to search for new drugs with analgesic and anti-inflammatory properties. OBJECTIVES: In this regard, the authors intend to investigate the ((2s,6s)-6-ethyl-tetrahydro-2h-pyran- 2-yl) methanol compound (LS20) on pain and acute inflammation. METHODS: Male Swiss mice were evaluated using acetic acid-induced abdominal writhing, formalin, and tail-flick as models of nociceptive evaluation and edema paw, air pouch and cell culture as models of inflammatory evaluation besides the rotarod test for assessment of motor impairment. RESULTS: The compound showed an effect on the acetic acid-induced abdominal writhing, formalin and tail-flick tests. Studying the mechanism of action, reversion of the antinociceptive effect of the compound was observed from previous intraperitoneal administration of selective and non-selective opioid antagonists on the tail flick test. In addition, the compound induced an antiedematogenic effect and reduced leukocyte migration and the production of pro-inflammatory cytokines in the air pouch model. LS20 was able to maintain cell viability, in addition to reducing cell production of TNF-α and IL-6. CONCLUSION: In summary, the LS20 compound presented an antinociceptive effect, demonstrating the participation of the opioid system and an anti-inflammatory effect related to the inhibition of pro-inflammatory cytokine production. The compound also demonstrated safety at the cellular level.
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Analgésicos , Anti-Inflamatórios , Dor , Piranos , Animais , Masculino , Camundongos , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Piranos/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Dor/tratamento farmacológico , Humanos , Inflamação/tratamento farmacológico , Metanol/química , Ácido Acético , Edema/tratamento farmacológico , Edema/induzido quimicamente , Citocinas/metabolismoRESUMO
Salvia semiatrata Zucc. (Lamiaceae) is endemic to Oaxaca, Mexico, and is known for its analgesic properties. Terpenoids and phenolic compounds with antinociceptive potential have been characterised from this species. The aim of this research was to determine the variation in terpenoids and flavonoids in ethyl acetate extracts of S. semiatrata collected from ten different localities, as well as to evaluate the antinociceptive effect between plants with higher and lower contents of these secondary metabolites. Quantification of S. semiatrata compounds was performed via HPLC-DAD, whereas in vivo evaluation of the antinociceptive effect was performed via formalin test. The results showed that the most abundant groups of metabolites are oleanolic acid (89.60-59.20 µg/mg), quercetin (34.81-16.28 µg/mg), catechin (11.30-9.30 µg/mg), and 7-keto-neoclerodan-3,13-dien-18,19:15,16-diolide (7-keto) (8.01-4.76 µg/mg). Principal component and canonical correspondence analysis showed that the most contrasting localities in terms of compound content and climatic variables are Miahuatlán and Santiago Huauclilla. The differences in metabolite content between the two locations did not affect the antinociceptive effects evaluated at a dose of 300 mg/kg, p.o. In conclusion, the results indicate that S. semiatrata is effective in relieving pain, regardless of the site of collection, reinforcing its traditional use as analgesic.
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Research background: Extracts from grape pomace, including the wine, show many biological effects such as antioxidant and anti-inflammatory activities. Unfortunately, winemakers discard the bagasse, so the waste is not exploited, although it contains bioactive compounds with antioxidant and anti-inflammatory properties. The work aims to analyze the hydroethanolic extract of peels from Vitis labrusca agro-industrial waste and to evaluate its antinociceptive and anti-inflammatory properties. This study is relevant for reusing a residue and adding value to the grape economic chain. Experimental approach: A representative sample of pomace was obtained and the peels were used to produce the extract. The phenolic compounds were determined by mass spectrometry in multiple reaction monitoring mode and Folin-Ciocalteu colorimetric method, using gallic acid as standard. The biological analyses were carried out using mice orally treated with crude extract at doses of 30, 100 and 300 mg/kg. We evaluated mechanical hyperalgesia by the von Frey method, thermal heat hyperalgesia using a hot plate at 55 °C, paw edema using a pachymeter, and neutrophil recruitment by measurement of myeloperoxidase activity. The nephrotoxicity and hepatotoxicity were evaluated by biochemical analyses using blood samples that were collected after the Vitis labrusca administration. Results and conclusions: In all wet winemaking residues peel mass fraction was 75%, and in dry residues 59%. We identified nine anthocyanins (3-O-glucosides: peonidin, delphinidin, petunidin and malvidin; 3-p-coumaroyl-glucosides: cyanidin, peonidin, petunidin and malvidin, and malvidin-3,5-diglucoside), five flavonoids (apigenin-7-glucoside, luteolin-7-glucoside, quercetin-3-galactoside, isorhamnetin-3-glucoside and myricetin-3-rutinoside), and mass fraction of phenolic compounds, expressed as gallic acid equivalents, was 26.62 mg/g. In vivo assays showed that Vitis labrusca extract at mass fractions 100 and 300 mg/kg reduced carrageenan-induced mechanical and thermal hyperalgesia, 50% of the paw edema, and neutrophil recruitment. In addition, there were no indications of nephrotoxicity and hepatotoxicity. Our extract obtained from winemaking residue has analgesic and anti-inflammatory properties, related at least in part to the presence of phenolic compounds, and it is not toxic to renal and hepatic tissues. Novelty and scientific contribution: This bio-product can be used as an alternative to synthetic anti-inflammatory agents with the same pharmacological potential and fewer side effects. We demonstrated that Vitis labrusca winemaking waste can be used for the production of antinociceptive and anti-inflammatory products (nutraceutical, pharmaceutical and cosmetics) without toxicity, contributing to the environmental economy.
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This study offers a novel oral pregabalin (PG)-loaded drug delivery system based on chitosan and hypromellose phthalate-based polymeric nanocomposite in order to treat neuropathic pain (PG-PN). PG-PN has a particle size of 432 ± 20 nm, a polydispersity index of 0.238 ± 0.001, a zeta potential of +19.0 ± 0.9 mV, a pH of 5.7 ± 0.06, and a spherical shape. Thermal and infrared spectroscopy confirmed nanocomposite generation. PG-PN pharmacokinetics was studied after a single oral dose in male Wistar rats. PG-PN showed greater distribution and clearance than free PG. The antinociceptive effect of PG-PN in neuropathic pain rats was tested by using the chronic constriction injury model. The parameter investigated was the mechanical nociceptive threshold measured by the von Frey filaments test; PG-PN showed a longer antinociceptive effect than free PG. The rota-rod and barbiturate sleep induction procedures were used to determine adverse effects; the criteria included motor deficit and sedative effects. PG-PN and free PG had plenty of motors. PG-PN exhibited a less sedative effect than free PG. By prolonging the antinociceptive effect and decreasing the unfavorable effects, polymeric nanocomposites with pregabalin have shown promise in treating neuropathic pain.
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Aristolochia trilobata, popularly known as "mil-homens," is widely used for treatment of stomach aches, colic, asthma, pulmonary diseases, diabetes, and skin affection. We evaluated the antinociceptive and anti-inflammatory activities of the essential oil (EO) and the main constituent, 6-methyl-5-hepten-2-yl acetate (sulcatyl acetate, SA). EO and SA (1, 10, and 100 mg/kg, p.o.) were evaluated using chemical (formalin-induced licking) and thermal (hot-plate) models of nociception or inflammation (carrageenan-induced cell migration into the subcutaneous air pouch, SAP). The mechanism of antinociceptive activity was evaluated using opioid, cholinergic receptor antagonists (naloxone and atropine), or nitric oxide synthase inhibitor (L-NAME). EO and SA presented a central antinociceptive effect (the hot-plate model). In formalin-induced licking response, higher doses of EO and SA also reduced 1st and 2nd phases. None of the antagonists and enzyme inhibitor reversed antinociceptive effects. EO and SA reduced the leukocyte migration into the SAP, and the cytokines tumor necrosis factor and interleukin-1 (TNF-α and IL-1ß, respectively) produced in the exudate. Our results are indicative that EO and SA present peripheral and central antinociceptive and anti-inflammatory effects.
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:Machaerium hirtum (Vell.) Stellfeld (Fabaceae) known in Brazil as "jacaranda de espinho" or "espinheira santa nativa" is a medicinal plant commonly used in folk medicine to treat ulcers, cough and diarrhea. This study aimed to investigate the anti-inflammatory and antinociceptive effects of hydroalcoholic extracts from M. hirtum twig (HEMh) using in vivo experimental models of nociception through the involvement of transient receptor potential channels, acid-sensing ion channel (ASIC), nitrergic, opioidergic, glutamatergic, and supraspinal pathways. Our results revealed an antinociceptive effect of HEMh mediated by the opioidergic, L-arginine-nitric oxide and glutamate systems, as well as by interactions with TRPA1/ASIC channels. The anti-inflammatory effect of HEMh evaluated with a xylene-induced ear edema and by the involvement of arachidonic acid and prostaglandin E2 (PGE2) showed involvement of the COX pathway, based on observed decreases in PGE2 levels. A phytochemical investigation of the HEMh led to the isolation of α-amyrin, ß-amyrin, allantoin, apigenin-7-methoxy-6-C-ß-D-glucopyranoside, and apigenin-6-C-ß-D-glucopyranosyl-8-C-ß-D-xylopyranoside. In conclusion, the acute oral administration of HEMh inhibits the nociceptive behavioral response in animals through the nitrergic, opioid, glutamatergic pathways, and by inhibition of the TRPA1 and ASIC channels, without causing locomotor dysfunction. In addition, its anti-inflammatory effect is associated with the COX pathway and decreased PGE2 levels.
Assuntos
Dor Aguda/tratamento farmacológico , Fabaceae/química , Inflamação/tratamento farmacológico , Dor Aguda/complicações , Analgésicos Opioides/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ácido Araquidônico , Arginina/metabolismo , Peso Corporal/efeitos dos fármacos , Dinoprostona/metabolismo , Edema/tratamento farmacológico , Etanol , Feminino , Formaldeído , Glutamatos/metabolismo , Indometacina/efeitos adversos , Inflamação/complicações , Canais Iônicos/metabolismo , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Óxido Nítrico/metabolismo , Nociceptividade/efeitos dos fármacos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Testes de Toxicidade Aguda , Úlcera/induzido quimicamente , Úlcera/complicações , Úlcera/tratamento farmacológico , XilenosRESUMO
BACKGROUND: There is a wide range of animal models available today for studying chronic pain associated with a variety of etiologies and an extensive list of clinical manifestations of peripheral neuropathies. Photobiomodulation is a new tool for the treatment of pain in a convenient, noninvasive way. OBJECTIVE: The aim of this work is to elucidate the effects of infrared light-emitting diodes (LEDs) on behavioral responses to nociceptive stimuli in chronic pain models. METHODS: Forty-eight Swiss male mice weighing 25 to 35 g were used. Two chronic pain models, ischemia-reperfusion (IR) and spared spinal nerve injury, were performed and then treated with infrared LED irradiation (390 mW, 890 nm, 17.3 mW/cm2 , 20.8 J/cm2 , for 20 minutes). The behavioral tests used were a mechanical hypersensitivity test von Frey test) and a cold allodynia test (acetone test). RESULTS: The results showed that, in the IR model, the infrared LED had a significant effect on mechanical stimulation and cold allodynia on every day of treatment. In the spared nerve injury model, an analgesic effect was observed on every treatment day (when started on the 3rd and 7th days after the surgery). In both models, the effect was abolished when the treatment was interrupted. CONCLUSIONS: These findings suggest that photobiomodulation therapy may be a useful adjunct treatment for chronic pain.
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Hiperalgesia , Raios Infravermelhos , Neuralgia , Nervos Periféricos/efeitos da radiação , Animais , Dor Crônica/etiologia , Modelos Animais de Doenças , Hiperalgesia/etiologia , Masculino , Camundongos , Neuralgia/etiologia , Traumatismos dos Nervos Periféricos/complicações , Traumatismo por Reperfusão/complicaçõesRESUMO
Recent findings have demonstrated new therapeutic functions of cardiotonic steroids, a process that is termed drug repositioning. Despite the confirmed anti-inflammatory effects of cardiotonic steroids, their clinical use has been discouraged due to toxicity related to inhibition of the Na+/K+ ATPase. A novel synthetic compound derived from digoxin, 21benzylidene digoxin (21BD), does not inhibit this enzyme. Herein, we evaluated the anti-inflammatory and antinociceptive effects and acute toxicity of 21BD. Murine (Swiss mice) models of paw oedema induced by carrageenan, acetic acid-induced abdominal writhing, and formalin and acute toxicity tests were used. Oral administration of 21BD (0.3â¯mg/kg) showed a significant and prolonged inhibition of paw oedema. Histological analysis demonstrated a reduction in inflammatory cells and expression of inducible nitric oxide synthase (iNOS) in footpads 6â¯h after administration of carrageenan. 21BD (0.3â¯mg/kg) also reduced the levels of tumour necrosis factor (TNF)-α 2 and 4â¯h after carrageenan. 21BD demonstrated antinociceptive activity, inhibiting abdominal writhes at all tested doses. However, in the formalin test, 21BD did not present antinociceptive activity. In the acute toxicity test, 21BD did not cause symptoms of toxicity or mortality. The present study demonstrated, for the first time, that 21BD is safe and exhibits a marked anti-inflammatory activity in acute local inflammation. This effect might be a consequence of its ability to inhibit the release of the PMN leucocyte-derived mediators, including TNF-α, and iNOS expression as well as its inhibitory effect on oedema and PMN leucocyte infiltration.
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Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Digoxina/análogos & derivados , Analgésicos/química , Animais , Anti-Inflamatórios/química , Carragenina/toxicidade , Digoxina/administração & dosagem , Digoxina/química , Digoxina/farmacologia , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Indometacina/farmacologia , Masculino , Camundongos , Estrutura Molecular , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Testes de Toxicidade , Fator de Necrose Tumoral alfa/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Schinopsis brasiliensis is a native plant from Brazil, popularly used in folk medicine to relieve pain and treat inflammation. This study evaluated the antinociceptive and anti-inflammatory activities and antioxidant properties of the hydroethanol extract (HEE) and ethyl acetate fraction (EAF) obtained from S. brasiliensis bark. MATERIALS AND METHODS: The HEE and EAF of S. brasiliensis bark (10, 30 and 100mg/kg, p.o.) were evaluated using models of analgaesia (formalin-induced licking and hot-plate models) or inflammation (licking response by formalin-induced and carrageenan-induced cell migration into the subcutaneous air pouch). The antioxidant activities of HEE and EAF (50, 100 and 200µg/ml) were evaluated using the lipoperoxidation method induced in egg yolk by 2'-azobis(2-amidinopropane) dihydrochloride (AAPH) and FeSO4. RESULTS: HEE and EAF presented a central antinociceptive effect (at 100mg/kg dose), increasing the baseline and area under the curve in the hot plate model. EAF (100mg/kg) significantly reduced (p< 0.005) the pain response in the first (45%) and second (35%) phases of the formalin-induced licking model, while HEE (100mg/kg) reduced (38%) only the pain response in the second phase. Regarding anti-inflammatory activity, EAF (100mg/kg) also inhibited the inflammatory process induced by subcutaneous carrageenan injection in the SAP model, reducing the amount of the cytokine TNF-α produced. CONCLUSION: HEE and EAF from S. brasiliensis bark show pharmacological interest because they were able to inhibit the peripheral and central transmission of pain. Our data also suggest that the anti-inflammatory activity caused by EAF exposure occurs through the inhibition of the pro-inflammatory cytokine TNF-α, also reducing the spreading of the inflammatory processes by neutralizing reactive oxygen species, which are by-products in the biosynthesis of pain mediators.
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Anacardiaceae/química , Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Animais , Movimento Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Medição da Dor/efeitos dos fármacos , Casca de Planta/química , Extratos Vegetais/farmacologiaRESUMO
Arrabidaea brachypoda (DC) Bureau is a medicinal plant found in Brazil. Known as "cipó-una", it is popularly used as a natural therapeutic agent against pain and inflammation. This study evaluated the chemical composition and antinociceptive activity of the dichloromethane fraction from the roots of A. brachypoda (DEAB) and its mechanism of action. The chemical composition was characterized by high-performance liquid chromatography, and this fraction is composed only of dimeric flavonoids. The antinociceptive effect was evaluated in formalin and hot plate tests after oral administration (10-100 mg/kg) in male Swiss mice. We also investigated the involvement of TRPV1 (transient receptor potential vanilloid 1), TRPA1 (transient receptor potential ankyrin 1), TRPM8 (transient receptor potential melastatin 8), and ASIC (acid-sensing ion channel), as well as the opioidergic, glutamatergic, and supraspinal pathways. Moreover, the nociceptive response was reduced (30 mg/kg) in the early and late phase of the formalin test. DEAB activity appears to involve the opioid system, TRPM8, and ASIC receptors, clearly showing that the DEAB alleviates acute pain in mice and suggesting the involvement of the TRPM8 and ASIC receptors and the opioid system in acute pain relief.
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Canais Iônicos Sensíveis a Ácido/metabolismo , Analgésicos/uso terapêutico , Bignoniaceae/química , Dor/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Canais de Cátion TRPM/metabolismo , Analgésicos/química , Analgésicos/isolamento & purificação , Analgésicos/farmacologia , Animais , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Dor/metabolismo , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Plantas Medicinais/químicaRESUMO
OBJECTIVE: The aim of this study was to evaluate the antinociceptive activity of the methanol extract of Tabebuia hypoleuca stems (THME). MATERIALS AND METHODS: The animals were divided into 5 groups of 8 mice for each test (negative controls, positive controls, and 3 groups treated with THME at doses of 150, 300, and 500 mg/kg, p.o.). The antinociceptive effect of THME was evaluated using the writhing, formalin, tail flick, and hot plate models in mice. RESULTS: In the writhing test, THME (150, 300, and 500 mg/kg) produced significantly (p < 0.001) fewer writhes induced by acetic acid than in the control group. In the formalin test, the licking time for THME at doses of 300 and 500 mg/kg was signiï¬cantly shorter (p < 0.001) compared to the control group in the first phase of the formalin test, whereas in the second phase only the dose of 500 mg/kg showed an antinociceptive effect. In addition, THME at doses of 300 and 500 mg/kg significantly increased the latency time in the tail flick test (p < 0.05 and p < 0.001, respectively) and in the hot plate test (p < 0.01 and p < 0.001, respectively) compared to the control group. CONCLUSIONS: These results show that THME had antinociceptive activity using several models of nociception, and they suggest that the effect is mediated by the participation of both peripheral and central antinociceptive mechanisms.
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Analgésicos/farmacologia , Extratos Vegetais/farmacologia , Tabebuia/efeitos dos fármacos , Ácido Acético , Análise de Variância , Animais , Cuba , Feminino , Masculino , Metanol , Camundongos , Camundongos Endogâmicos BALB C , Dor/tratamento farmacológico , Medição da Dor , Ratos , Ratos Sprague-Dawley , Tabebuia/toxicidade , CaudaRESUMO
The molecular modification and synthesis of compounds is vital to discovering drugs with desirable pharmacological and toxicity profiles. In response to pyrazole compounds' antipyretic, analgesic, and anti-inflammatory effects, this study sought to evaluate the analgesic, anti-inflammatory, and vasorelaxant effects, as well as the mechanisms of action, of a new pyrazole derivative, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole. During the acetic acid-induced abdominal writhing test, treatments with 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole reduced abdominal writhing, while during the formalin test, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole reduced licking times in response to both neurogenic pain and inflammatory pain, all without demonstrating any antinociceptive effects, as revealed during the tail flick test. 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole also reduced carrageenan-induced paw edema and cell migration during the carrageenan-induced pleurisy test. As demonstrated by the model of the isolated organ, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole exhibits a vasorelaxant effect attenuated by Nω-nitro-l-arginine methyl ester, 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one, tetraethylammonium or glibenclamide. 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole also blocked CaCl2 -induced contraction in a dose-dependent manner. Suggesting a safe toxicity profile, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole reduced the viability of 3T3 cells at higher concentrations and was orally tolerated, despite signs of toxicity in doses of 2000 mg/kg. Lastly, the compounds' analgesic activity might be attributed to the involvement of the NO/cGMP pathway and K+ channels observed in the vasorelaxant effect.
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Pirazóis/química , Pirazóis/farmacologia , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antipiréticos/farmacologia , Técnicas In Vitro , Masculino , Camundongos , Ratos , Ratos WistarRESUMO
The combination of pomegranate seed oil and ketoprofen in nanoemulsions aiming to improve the antinociceptive effect was evaluated according to the writhing test and Complete Freud's Adjuvant induced paw inflammation in mice. The formulations showed adequate characteristics and improved ketoprofen's photostability against UVC radiation exposure. The dialysis bag technique showed that 100% of the drug was released from the nanoemulsions after 3h and the oil amount had no influence on the releasing. Furthermore, time- and dose-response curves were obtained to determine the antinociceptive effect of the formulations. In the post-test, the nanoemulsion containing ketoprofen significantly reduced abdominal constrictions in time-response curve, showing effect up to 12h while the free ketoprofen showed effect up to 3h. In addition, the blank nanoemulsion presented a reduction of abdominal constriction up to 1h of pre-treatment. Regarding the dose-response curve, the free ketoprofen presents effect at 0.5mg/Kg dose and nanoemulsion at 1.0mg/Kg dose. Time- and dose-response curves were performed to determine the antinociceptive effect in inflammatory pain. After the evaluation of mechanical allodynia testing at the Von Frey Hair, the free ketoprofen showed effect up to 6h while nanoemulsions presented effect up to 10h. Moreover, acute toxicity was performed with ALT and AST activity evaluations and urea levels. After 7 days of treatment, no toxic effects for nanoemulsions were found. In conclusion, ketoprofen-loaded pomegranate seed oil nanoemulsions presented adequate characteristics and a high antinociceptive activity in the animal models tested.
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Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Emulsões/química , Lythraceae/química , Nanopartículas/química , Óleos de Plantas/uso terapêutico , Raios Ultravioleta , Abdome/patologia , Ácido Acético , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Constrição Patológica , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Adjuvante de Freund , Inflamação/complicações , Inflamação/tratamento farmacológico , Injeções , Cetoprofeno/administração & dosagem , Cetoprofeno/farmacologia , Cetoprofeno/uso terapêutico , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Dor/complicações , Dor/tratamento farmacológico , Óleos de Plantas/administração & dosagem , Óleos de Plantas/farmacologia , Sementes/química , Testes de Toxicidade AgudaRESUMO
Structurally different water-insoluble (1â3),(1â6) ß-D-glucans were isolated from aqueous and alkaline extracts of the mushroom-forming ascomycete Cookeina tricholoma, a wild edible mushroom found in Brazilian Amazon forest. The structures showed different substitution patterns, which may influence their extractability and consequently their conformation in solution, and different MW (4.3×10(5)Da, 3.7×10(5)Da and 8.2×10(5)Da, for ICW-Ct, IHW-Ct and IK2-Ct, respectively). The main-chains are composed of (1â3)-linked ß-D-Glcp units O-6 substituted by side chains with different lengths of (1â6)-linked ß-d-Glcp units (ICW-Ct and IHW-Ct) or by a combination of (1â6)-linked ß-D-Glcp units and single units of ß-D-Glcp (IK2-Ct). ß-D-glucans with similar MW and showing only (1â6)-linked ß-D-Glcp units as side chains (ICW-Ct and IHW-Ct) showed significant inhibition of neurogenic pain, 69±11 and 57±11% at the dose of 10mgkg(-1), respectively, in the model of nociception induced by intraplantar injection of formalin.
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Analgésicos/química , Ascomicetos/química , Polissacarídeos Fúngicos/química , Glucanos/química , Analgésicos/farmacologia , Animais , Feminino , Polissacarídeos Fúngicos/farmacologia , Glucanos/farmacologia , Camundongos , Nociceptividade/efeitos dos fármacosRESUMO
The present study aimed to investigate the antinociceptive and anti-inflammatory effects of the cyclic dipeptide cyclo-Gly-Pro (CGP) in mice. Antinociceptive activity was assessed by employing different pain models, such as formalin test, acetic acid-induced writhing, hot plate test, and carrageenan-induced hyperalgesia, in mice. The number of c-Fos-immunoreactive cells in the periaqueductal gray (PAG) was evaluated in CGP-treated mice. Anti-inflammatory activity was evaluated using paw oedema induced by carrageenan, compound 48/80, serotonin, and prostaglandin E2 (PGE2) and analyzed by plethysmometry. Quantitation of myeloperoxidase (MPO) in the paw was carried out to analyze the presence of neutrophils in the tissue. Intraperitoneal injection of CGP produced a significant inhibition in both neurogenic and inflammatory phases of formalin-induced pain. The antinociceptive effect of CGP, evaluated in the acetic acid-induced writhing test, was detected for up to 6 h after treatment. Further, in the hot plate test, antinociceptive behaviour was evoked by CGP, and this response was inhibited by naloxone. Animals treated with CGP did not present changes in motor performance. In CGP-treated mice there was an increase in the number of c-Fos-positive neurons in the periaqueductal gray. In another set of experiments, CGP attenuated the hyperalgesic response induced by carrageenan. Furthermore, CGP also reduced the carrageenan-increased MPO activity in paws. In addition, CGP also reduced the paw oedema evoked by compound 48/80, serotonin, and PGE2 . Taken together, these results may support a possible therapeutic application of the cyclic dipeptide cyclo-Gly-Pro toward alleviating nociception and damage caused by inflammation conditions.
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Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Comportamento Animal/efeitos dos fármacos , Nociceptividade/efeitos dos fármacos , Peptídeos Cíclicos/farmacologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperalgesia/tratamento farmacológico , Inflamação/tratamento farmacológico , Masculino , Camundongos , Peptídeos Cíclicos/uso terapêutico , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Substância Cinzenta Periaquedutal/metabolismo , Teste de Desempenho do Rota-RodRESUMO
A structural characterization of polysaccharides obtained by aqueous extraction of ripe pulp of the edible exotic tropical fruit named tamarillo (Solanum betaceum) was carried out. After fractionation by freeze-thaw and α-amylase treatments, a fraction containing a mixture of highly-methoxylated homogalacturonan and of arabinogalactan was obtained. A degree of methylesterification (DE) of 71% and a degree of acetylation (DA) of 1.3% was determined by (1)H NMR spectroscopy and spectrophotometric quantification, respectively. A type I arabinogalactan was purified via Fehling precipitation and ultrafiltration through 50 kDa (cut-off) membrane. Its chemical structure was performed by sugar composition, HPSEC, methylation, carboxy-reduction and (13)C NMR spectroscopy analysis. Intraperitoneal administration of the arabinogalactan did not reduce the nociception induced by intraplantar injection of 2.5% formalin in mice, but significantly reduced the number of abdominal constrictions induced by 0.6% acetic acid, indicating that fraction has an antinociceptive effect on the visceral inflammatory pain model.
Assuntos
Analgésicos , Frutas/química , Galactanos , Dor/tratamento farmacológico , Solanum , Ácido Acético , Analgésicos/química , Analgésicos/isolamento & purificação , Analgésicos/uso terapêutico , Animais , Feminino , Formaldeído , Galactanos/química , Galactanos/isolamento & purificação , Galactanos/uso terapêutico , Metilação , Camundongos , Estrutura Molecular , Peso Molecular , Monossacarídeos/análise , Dor/induzido quimicamente , FitoterapiaRESUMO
BACKGROUND: Encholirium spectabile is a species found in outcrops rocky throughout the Brazilian Caatinga. OBJECTIVE: This study was carried out to evaluate the antinociceptive effects of ethanolic extract of the leaves from E. spectabile (Es-EtOH) in mice using chemical and thermal models of nociception. MATERIAL AND METHODS: HPLC was used to determine the fingerprint chromatogram. The Es-EtOH was examined for its antinociceptive activity at the doses of 100, 200 and 400 mg/kg intraperitoneal (i.p.). The evaluation of antinociceptive activity was carried out by the acetic acid-induced writhing, formalin and hot plate tests in mice. Rota-rod test was used for the evaluation of motor coordination. RESULTS: In the acetic acid-induced writhing test, the Es-EtOH (100, 200 and 400 mg/kg, i.p.) reduced the number of writhings by 68.59, 79.33 and 65.28%, respectively. Additionally, Es-EtOH (100, 200 and 400 mg/kg, i.p.) decreased by 34.14, 52.61 and 60.97% the paw licking time in the first phase, as well as 89.56, 79.90 and 96.71% in the second phase of the formalin test, respectively. Es-EtOH also showed effect in the hot plate test, since increased the latency time at dose of 100 mg/kg after 60 minutes. In addition, Es-EtOH did not impair motor coordination. The presence of phenolic compounds in the extract was confirmed using HPLC. These results indicate that Es-EtOH has antinociceptive activity, probably of peripheral origin. The mechanism involved is not completely understood but, at least in part there is the participation of opioid receptors.
RESUMO
Previous studies on the genus Clusia have shown anti-inflammatory and antiproliferative effects of the leaf extracts, but its antinociceptive activity has never been characterized. In the present study, the antinociceptive activity of the hexane extract of the leaves of Clusia nemorosa G. Mey, called HECn, was examined. Antinociceptive activity was evaluated using acetic acid-induced writhing, formalin, and hot-plate tests. All experiments were carried out on male Swiss mice. The extract (1-400 mg·kg(-1)), given by intraperitoneal route (i.p.) 1 h prior to testing, produced a dose-dependent inhibition on the number of abdominal writhings, with an ID50 of 62 mg·kg(-1). In addition, HECn was able to prevent the visceral pain induced by acetic acid in mice for at least 2 h. In the formalin test, HECn had no effect in the first phase, but produced an analgesic effect on the second phase with the inhibition of licking time. The HECn did not show a significant analgesic effect in the hot plate test. Pretreatment with yohimbine attenuated the antinociceptive effect induced by HECn in the writhing test. However, naloxone, atropine, or haloperidol did not affect antinociception induced by HECn in the writhing test. Together, these results indicate that the extract from the leaves of Clusia nemorosa produces antinociception in models of chemical pain through mechanisms that suggest participation of the adrenergic systems pathway.
Assuntos
Adrenérgicos/administração & dosagem , Analgésicos/administração & dosagem , Clusia/química , Dor/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Animais , Humanos , Masculino , Camundongos , Nociceptividade/efeitos dos fármacos , Dor/psicologia , Fitoterapia , Folhas de Planta/químicaRESUMO
The ethanol extract from Vernonia polyanthes leaves (EEVP) was investigated for antinociceptive and anti-inflammatory effects at the doses (p.o.) of 100, 200 and 400 mg/kg in animal models. The extract reduced the number of abdominal contortions by 16.75% and 31.44% at a dose of 200 and 400 mg/kg, respectively. The results obtained showed that EEVP exerted a significant antinociceptive effect in the two phases of formalin. The EEVP increased the reaction time on a hot plate at the doses of 100, 200 and 400 mg/kg after 90 min of treatment. The paw edema was reduced by EEVP at the doses of 100, 200 and 400 mg/kg after 4 h of application of carrageenan. Doses of 200 and 400 mg/kg, administered 4 h before the carrageenan injection, significantly reduced the exudate volume (29.25 and 45.74%, respectively) and leukocyte migration (18.19 and 27.95%, respectively). These results suggest that V. polyanthes can be an active source of substances with antinociceptive and anti-inflammatory activities.
Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Extratos Vegetais/uso terapêutico , Folhas de Planta/metabolismo , Vernonia/metabolismo , Animais , Carragenina , Edema/tratamento farmacológico , Etanol/química , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Masculino , Camundongos , Dor/induzido quimicamente , Dor/tratamento farmacológico , Manejo da Dor , Medição da Dor , Ratos , Ratos WistarRESUMO
Chrysopogon zizanioides (L.) Roberty, Poaceae, is a plant widely used in northeast Brazil in folk medicine for the treatment of various pathological conditions, including inflammatory pain. The present study evaluated the antinociceptive and anti-inflammatory effects of C. zizanioides essential oil (EO) in rodents. EO was further characterized by GC/MS. The major components of EO were identified as khusimol (19.57%), E-isovalencenol (13.24%), α-vetivone (5.25%), β-vetivone (4.87%) and hydroxy-valencene (4.64%). Following intraperitoneal injection (i.p.), EO at 50 and 100 mg/kg significantly reduced the number of writhes (51.9 and 64.9%, respectively) and the number of paw licks during phase 2 (56.7 and 86.2%, respectively) of a formalin model when compared to control group animals. However, EO-treated mice were ineffective at all doses in hot-plate and rota-rod tests. The EO inhibited the carrageenan-induced leukocyte migration to the peritoneal cavity in a dose-dependent manner (34.7, 35.4, and 62.5% at doses of 25, 50 and 100 mg/kg, respectively). In the paw edema test, the EO (100 mg/kg) inhibited all three phases of the edema equally well, suggesting that the EO has a non-selective inhibitory effect on the release or actions of these mediators. Our results suggest possible antinociceptive and anti-inflammatory effects of the EO.