RESUMO
BACKGROUND AND PURPOSE: Postoperative pain is one of the most common manifestations of acute pain and is an important problem faced by patients after surgery. Moreover, neuronal trauma or chemotherapeutic treatment often causes neuropathic pain, which induces disabling and distressing symptoms. At present, treatments of both painful conditions are inadequate. α-Spinasterol, which is well characterized as a transient receptor potential vanilloid 1 antagonist, has anti-inflammatory, antioxidant and antinociceptive effects. Therefore, we investigated its antinociceptive potential on postoperative and neuropathic pain, as well as its effect on COX-1 and COX-2 activities. EXPERIMENTAL APPROACH: Nociceptive responses in a postoperative pain model (surgical incision-induced) or different neuropathic pain models (trauma or chemotherapy-induced) were investigated in mice. KEY RESULTS: Oral administration of α-spinasterol reduced postoperative pain, when given as a pre- (0.5 h before incision) or post-treatment (0.5 h after incision), and reduced cell infiltration in the injured tissue. α-Spinasterol also reduced the mechanical allodynia induced by partial sciatic nerve ligation and the mechanical and cold allodynia induced by paclitaxel. Moreover, α-spinasterol inhibited COX-1 and COX-2 enzyme activities without altering the body temperature of animals. Importantly, α-spinasterol did not alter spontaneous or forced locomotor activity. Furthermore, it did not cause gastric damage or liver and kidney changes, nor did it alter cell viability in the cerebral cortex and spinal cord slices of mice. CONCLUSION AND IMPLICATIONS: α-Spinasterol is an effective and safe COX inhibitor with antinociceptive effects in postoperative and neuropathic pain models. Therefore, it is an interesting prototype for the development of novel analgesic drugs.
Assuntos
Neuralgia/tratamento farmacológico , Dor Pós-Operatória/tratamento farmacológico , Estigmasterol/análogos & derivados , Dor Aguda/tratamento farmacológico , Administração Oral , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Analgésicos/toxicidade , Animais , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/toxicidade , Inibidores de Ciclo-Oxigenase/administração & dosagem , Inibidores de Ciclo-Oxigenase/farmacologia , Inibidores de Ciclo-Oxigenase/toxicidade , Modelos Animais de Doenças , Hiperalgesia/tratamento farmacológico , Masculino , Camundongos , Estigmasterol/administração & dosagem , Estigmasterol/farmacologia , Estigmasterol/toxicidade , Canais de Cátion TRPV/antagonistas & inibidores , Fatores de TempoRESUMO
Arthritis is a chronic inflammatory disease which reduces the life quality of affected individuals. Therapeutic tools used for treating inflammatory pain are associated with several undesirable effects. Buddleja thyrsoides Lam., known as 'Barbasco' or 'Cambara', is mostly used in several disorders and possesses antirheumatic, anti-inflammatory, and analgesic properties. Here, we investigated the antinociceptive and anti-inflammatory effects of the B. thyrsoides crude extract applied orally and topically in acute pain models and an arthritic pain model induced by complete Freund's adjuvant (CFA) paw injection in male mice (25-30â g). The high-performance liquid chromatography (HPLC) of the B. thyrsoides extract crude revealed the presence of the lupeol, stigmasterol, and ß-sitosterol. The stability study of the B. thyrsoides gel did not show relevant changes at low temperatures. The oral treatment with the B. thrysoides extract prevented the capsaicin-induced spontaneous nociception and the acetic acid-induced abdominal writhing, but did not alter the thermal threshold in the tail immersion test. The B. thyrsoides antinociceptive effect was not reversed by naloxone in the capsaicin test. The B. thyrsoides oral or topical treatment reversed the CFA-induced mechanical allodynia and thermal hyperalgesia with maximum inhibition (Imax) of 69 ± 6 and 68 ± 5% as well as 78 ± 15 and 87 ± 12%, respectively. Moreover, the topical but not oral treatment inhibited the CFA-induced cell infiltration, but did not reduce the paw edema significantly. The oral treatment with B. thyrsoides did not cause adverse effects. These findings suggest that the oral or topical treatment with B. thyrsoides presents antinociceptive actions in an arthritic pain model without causing adverse effects.
Assuntos
Analgésicos não Narcóticos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Experimental/tratamento farmacológico , Buddleja/química , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Dor Aguda/tratamento farmacológico , Administração Cutânea , Administração Oral , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/efeitos adversos , Analgésicos não Narcóticos/química , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/química , Brasil , Buddleja/crescimento & desenvolvimento , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Etnofarmacologia , Géis , Temperatura Alta/efeitos adversos , Masculino , Camundongos , Triterpenos Pentacíclicos/administração & dosagem , Triterpenos Pentacíclicos/efeitos adversos , Triterpenos Pentacíclicos/análise , Triterpenos Pentacíclicos/uso terapêutico , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Extratos Vegetais/química , Folhas de Planta/crescimento & desenvolvimento , Sitosteroides/administração & dosagem , Sitosteroides/efeitos adversos , Sitosteroides/análise , Sitosteroides/uso terapêutico , Estigmasterol/administração & dosagem , Estigmasterol/efeitos adversos , Estigmasterol/análise , Estigmasterol/uso terapêutico , ViscosidadeRESUMO
Piptoporus betulinus has been used in folk medicine for millennia. However, no data currently exist regarding its potential cardiovascular activity. In this work, the crude ethanolic extract and fractions (hexane, ethyl acetate, and water) with increased polarity from the partitioning process, as well as stigmasterol (the major metabolite isolated from P. betulinus), were administered orally at different doses to normotensive male Wistar rats an hour before recording mean arterial pressure, heart rate, renal blood flow, renal vascular conductance, arterial blood flow, and arterial vascular conductance. The acute oral administration of crude ethanolic extract and all fractions did not alter mean arterial pressure when compared with the control group, which received a vehicle. In addition, subchronic (14 days) oral administration of crude ethanolic extract, fractions, and stigmasterol did not alter cardiovascular parameters. In conclusion, our findings demonstrate that oral administration of organic extracts of P. betulinus did not induce cardiovascular alterations.
Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Misturas Complexas/administração & dosagem , Polyporales/química , Estigmasterol/administração & dosagem , Administração Oral , Animais , Misturas Complexas/isolamento & purificação , Masculino , Ratos Wistar , Estigmasterol/isolamento & purificaçãoRESUMO
OBJECTIVE: Phytosterols have been used alone, or combined with lipid-altering drugs, to reduce cholesterol levels and the burden of cardiovascular disease. Considerable variation in the composition of phytosterols exists and its consumption, in a regular diet, by the Brazilian population is still unknown. Thus, the aim of the present study was to determine the phytosterols content of the most consumed plant foods and to estimate the phytosterols intake by this population. METHODS: Intake of plant foods of a representative population of the city of São Paulo (n = 1609), randomly selected on the basis of the Brazilian Institute for Geography and Statistics census data (2010), was obtained by a food frequency questionnaire (FFQ). Foods were chosen on the basis of the Consume Expenditure Survey (2002-2003) and from answers to the FFQ. Phytosterols composition of most consumed greens, legumes, cereals, and seeds, fruits, and vegetable oils was determined by gas chromatography (flame ionization detection). Daily phytosterols intake was estimated in terms of mg per 100 g (mg/100 g(-1)) of edible portion. Underreporters and overreporters were excluded. RESULTS: Mean (SE) daily phytosterols intake in the diet of the study population was 100.6 (1.2) mg, with ß-sitosterol as the largest sterol component (65.4%), followed by campesterol (23.2%), and stigmasterol (10%). No significant changes in daily phytosterols intake were observed after exclusion of underreporters and overreporters. Considerable variation was observed in phytosterols content among the most consumed plant foods. CONCLUSIONS: Analysis of phytosterols composition in most consumed plant foods has shown that phytosterols content varied among food groups. Dietary intake of phytosterols in a large population of the city of São Paulo is in the same range of some countries.
Assuntos
Colesterol/análogos & derivados , Comportamento Alimentar , Fitosteróis/administração & dosagem , Sitosteroides/administração & dosagem , Estigmasterol/administração & dosagem , Adulto , Idoso , Brasil , Colesterol/administração & dosagem , Colesterol/análise , Colesterol/sangue , Cromatografia Gasosa , Estudos Transversais , Grão Comestível/química , Fabaceae/química , Feminino , Frutas/química , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Fitosteróis/análise , Óleos de Plantas/química , Plantas Comestíveis/química , Sementes/química , Sitosteroides/análise , Estigmasterol/análise , Inquéritos e Questionários , Verduras/química , Adulto JovemRESUMO
Arnica (Heterotheca inuloides) is a widely used medicinal plant in México; it has been recognized as anti-inflammatory, analgesic, cytotoxic, scavenger of superoxide anion and also as a preventive of lipid peroxidation. In vivo studies have demonstrated a hepatoprotective action of the methanolic extract of this plant as well as of quercetin, one of its main components, and the evidence obtained pointed out to an antioxidant mechanism. In this work, we focused on the free radical scavenging capacity of acetonic and methanolic extracts of H. inuloides in comparison with reference compounds. The two extracts were 2-12 times more effective (IC50, microg/mL) than the reference compounds to cope with the following radicals or molecules tested: 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(+)), 2,2-diphenyl-1-picrylhydrazyl (DPPH), peroxynitrite (ONOO(-)), superoxide (O2(-)), singlet oxygen ((1)O(2)), hypochlorous acid (HOCl), hydrogen peroxide (H2O2), hydroxyl (OH). Additionally, five secondary metabolites isolated from the methanolic extract displayed potent concentration-dependent antioxidant effects against reactive oxygen species produced in vitro (IC50 values in the range of 0.018-4.31mg/mL). d-Chiro-inositol showed the higher antioxidant effect against O2(-), H2O2 and OH while spinasterol and quercetin were the most active against (1)O(2) and ONOO(-), respectively. The antioxidant properties of the extracts and metabolites tested partially support the wide use of this plant in traditional medicine.
Assuntos
Antioxidantes/farmacologia , Asteraceae/química , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/administração & dosagem , Antioxidantes/isolamento & purificação , Relação Dose-Resposta a Droga , Peróxido de Hidrogênio/metabolismo , Concentração Inibidora 50 , Medicina Tradicional , México , Extratos Vegetais/administração & dosagem , Quercetina/administração & dosagem , Quercetina/isolamento & purificação , Quercetina/farmacologia , Estigmasterol/administração & dosagem , Estigmasterol/análogos & derivados , Estigmasterol/isolamento & purificação , Estigmasterol/farmacologiaRESUMO
The present study assessed the possible antinociceptive action of the hydroalcoholic extract, fractions and pure compounds obtained from the aerial parts of Baccharis illinita DC (Asteraceae) in behavioural models of chemical nociception in mice. The hydroalcoholic extract and fractions (hexane and aqueous but not EtOAc fraction) obtained from B. illinita (30-1000 mg/kg orally) produced a dose-related inhibition of the acetic acid-induced nociceptive response. However, the hexane fraction was more potent than the hydroalcoholic extract and the aqueous fraction. The hexane fraction derivatives baurenol, alpha-spinasterol and oleanolic acid (0.00001-10 mg/kg intraperitoneally) also caused potent inhibition of acetic acid-induced pain. The hexane fraction (300-1000 mg/kg orally) produced inhibition of both phases of formalin-induced pain. Moreover, the hexane fraction (30-600 mg/kg orally) also caused a dose-dependent inhibition of glutamate-induced pain. Nevertheless, the hexane fraction only at the dose of 300 mg/kg orally, produced partial inhibition of the paw oedema caused by carrageenan. Furthermore, the hexane fraction (300 mg/kg orally) caused inhibition of the nociceptive response induced by intrathecal injection of N-methyl-d-aspartic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, tumour necrosis factor-alpha and interleukin-1beta. In contrast, the hexane fraction did not affect the biting response induced by the metabotropic or ionotropic glutamatergic receptor agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid and kainate, respectively. In addition, the antinociception caused by the hexane fraction (300 mg/kg orally) in the acetic acid test was not affected by intraperitoneal treatment of mice with naloxone (a non-selective opioid receptor antagonist). The precise mechanism responsible for the antinociceptive effect of the hexane fraction remains unclear, but appears to be partly associated with an inhibition of glutamatergic transmission and an inhibition of pathways dependent on pro-inflammatory cytokines. Finally, baurenol, alpha-spinasterol and oleanolic acid have an important role in the antinociceptive effects of the hexane fraction. Moreover, the antinociceptive action demonstrated in the present study supports the ethnomedical uses of this plant.
Assuntos
Analgésicos/farmacologia , Baccharis/química , Dor/tratamento farmacológico , Extratos Vegetais/farmacologia , Analgésicos/administração & dosagem , Analgésicos/isolamento & purificação , Animais , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Camundongos , Ácido Oleanólico/administração & dosagem , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Medição da Dor , Componentes Aéreos da Planta , Extratos Vegetais/administração & dosagem , Receptores de Glutamato , Solventes/química , Estigmasterol/administração & dosagem , Estigmasterol/análogos & derivados , Estigmasterol/isolamento & purificação , Estigmasterol/farmacologia , Triterpenos/administração & dosagem , Triterpenos/isolamento & purificação , Triterpenos/farmacologiaRESUMO
Intravenous administration of the hexane extract of the bark of Anacardium occidentale (cashew) in normal, healthy dogs produced a significant lowering of the blood glucose levels. Pursuit of the hypoglycaemic principle(s) in the hexane extract resulted in the isolation and characterization of two compounds, stigmast-4-en-3-ol (1) and stigmast-4-en-3-one (2). These compounds were purified by chromatographic methods and the structures were characterized by spectroscopic methods. Both compounds produced significant hypoglycaemic activity after intravenous administration at a dose of 1.3 mg/kg body weight. The bark of the cashew plant, A. occidentale, exhibited a hypoglycaemic effect probably due to the presence of these compounds.