RESUMEN
Kahweol is a compound derived from coffee with reported antinociceptive effects. Based on the few reports that exist in the literature regarding the mechanisms involved in kahweol-induced peripheral antinociceptive action, this study proposed to investigate the contribution of the endocannabinoid system to the peripheral antinociception induced in rats by kahweol. Hyperalgesia was induced by intraplantar injection of prostaglandin E2(PGE2) and was measured with the paw pressure test. Kahweol and the drugs to test the cannabinoid system were administered locally into the right hind paw. The endocannabinoids were purified by open-bed chromatography on silica and measured by LC-MS. Kahweol (80 µg/paw) induced peripheral antinociception against PGE2-induced hyperalgesia. This effect was reversed by the intraplantar injection of the CB1 cannabinoid receptor antagonist AM251 (20, 40, and 80 µg/paw), but not by the CB2 cannabinoid receptor antagonist AM630 (100 µg/paw). Treatment with the endocannabinoid reuptake inhibitor VDM11 (2.5 µg/paw) intensified the peripheral antinociceptive effect induced by low-dose kahweol (40 µg/paw). The monoacylglycerol lipase (MAGL) inhibitor, JZL184 (4 µg/paw), and the dual MAGL/fatty acid amide hydrolase (FAAH) inhibitor, MAFP (0.5 µg/paw), potentiated the peripheral antinociceptive effect of low-dose kahweol. Furthermore, kahweol increased the levels of the endocannabinoid anandamide, but not of the other endocannabinoid 2-arachidonoylglycerol nor of anandamide-related N-acylethanolamines, in the plantar surface of the rat paw. Our results suggested that kahweol induced peripheral antinociception via anandamide release and activation of CB1 cannabinoid receptors and this compound could be used to develop new drugs for pain relief.
Asunto(s)
Diterpenos , Endocannabinoides , Analgésicos/farmacología , Animales , Café , Hiperalgesia/inducido químicamente , Hiperalgesia/tratamiento farmacológico , Ratas , Receptor Cannabinoide CB1 , Receptor Cannabinoide CB2RESUMEN
Establishing new animal models for the study of inflammation is very important in the process of discovering new drugs, since the inflammatory event is the basis of many pathological processes. Whereas rodent models have been the primary focus of inflammation research, we defend the zebrafish (Danio rerio) test as a feasible alternative for preclinical studies. Moreover, despite all the technological development already achieved by humanity, nature can still be considered a relevant source of new medicines. In this context, the aim of this work was to evaluate the anti-inflammatory effect of a substance isolated from the medicinal plant Annona crassilfora Mart, the peltatoside, in an inflammatory model of zebrafish. It was determined: (i) total leukocyte count in the coelomate exudate; (ii) N-acetyl-ß-d-glucuronidase (NAG); (iii) myeloperoxidase (MPO); (iv) and the histology of liver, intestine and mesentery. Peltotoside (25, 50 and 100 µg) and dexamethasone (25 µg) were administered intracelomatically (i.c.) 30 min before carrageenan (i.c.). Pretreatment with peltatoside at three doses significantly inhibited leukocyte recruitment in the coelomic cavity, and inhibited NAG and MPO activity against the action of Cg, in a similar manner as dexamethasone. However, some microlesions in the evaluated organs were detected. The dose of 25 µg showed an anti-inflammatory effect with lower undesirable effects in the tissues. Our results suggest that the zebrafish test was satisfactory in performing our analyzes and that the peltotoside has a modulatory action in reducing leukocyte migration.
Asunto(s)
Annona/química , Antiinflamatorios/farmacología , Modelos Animales de Enfermedad , Glicósidos/farmacología , Inflamación/tratamiento farmacológico , Extractos Vegetales/farmacología , Quercetina/análogos & derivados , Pez Cebra , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Glicósidos/administración & dosificación , Glicósidos/química , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Hojas de la Planta/química , Plantas Medicinales/química , Quercetina/administración & dosificación , Quercetina/química , Quercetina/farmacologíaRESUMEN
The Maytenus genus is a member of the Celastraceae family. Numerous medicinal uses were assigned to species of this genus, with the use of roots, bark, and leaves for the treatment of gastric ulcers, as anti-inflammatory, analgesic, antiallergic, antitumor, among others. Several studies have demonstrated that natural products derived from plants have an important role in the prevention and treatment of obesity. Accordingly, we evaluated the effect of Maytenus imbricata extracts in the treatment of obesity induced by diet rich in refined carbohydrate (HC). BALB/c mice were fed chow or HC diet for 8 weeks. At the beginning of the 9th week, the HC group was subdivided into three groups: (i) group of animals that continued to consume only HC diet; (ii) the group of animals fed HC diet supplemented with ethyl acetate extract of M. imbricata roots (HC + EAE); (iii) the group of animals fed HC diet supplemented with extract in hexane/ethyl ether (HC + HEE). The period of extracts supplementation was 4 weeks. It was observed that EAE and EHE when added to the HC diet modulated the metabolic and inflammatory changes, such as: reduced the adipocytes area, improved glucose intolerance, reduced the levels of triglycerides and resistin in serum, and the number of total leukocytes in blood. In the epididymal adipose tissue, the extracts reduced proinflammatory mediators' concentration. According to the results, it was concluded that the species Maytenus imbricata has the potential to be used for the treatment of obesity.
Asunto(s)
Celastraceae/química , Inflamación/tratamiento farmacológico , Maytenus/química , Enfermedades Metabólicas/tratamiento farmacológico , Extractos Vegetales/farmacología , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Carbohidratos/farmacología , Dieta/efectos adversos , Suplementos Dietéticos , Inflamación/metabolismo , Resistencia a la Insulina/fisiología , Masculino , Enfermedades Metabólicas/metabolismo , Ratones , Ratones Endogámicos BALB C , Triglicéridos/metabolismoRESUMEN
Orofacial pain is pain perceived in the face and/or oral cavity, generally caused by diseases or disorders of regional structures, by dysfunction of the nervous system, or through referral from distant sources. Treatment of orofacial pain is mainly pharmacological, but it has increased the number of reports demonstrating great clinical results with the use of non-pharmacological therapies, among them electroacupuncture. However, the mechanisms involved in the electroacupuncture are not well elucidated. Thus, the present study investigate the involvement of the nitric oxide synthase (NOS) and ATP sensitive K+ channels (KATP) in the antinociception induced by electroacupuncture (EA) at acupoint St36. Thermal nociception was applied in the vibrissae region of rats, and latency time for face withdrawal was measured. Electrical stimulation of acupoint St36 for 20 minutes reversed the thermal withdrawal latency and this effect was maintained for 150 min. Intraperitoneal administration of specific inhibitors of neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS) and a KATP channels blocker reversed the antinociception induced by EA. Furthermore, nitrite concentration in cerebrospinal fluid (CSF) and plasma, increased 4 and 3-fold higher, respectively, after EA. This study suggests that NO participates of antinociception induced by EA by nNOS, iNOS and ATP-sensitive K+ channels activation.
Asunto(s)
Puntos de Acupuntura , Electroacupuntura , Dolor Facial/terapia , Manejo del Dolor , Animales , Dolor Facial/fisiopatología , Calor/efectos adversos , Canales KATP/antagonistas & inhibidores , Canales KATP/fisiología , Masculino , Óxido Nítrico Sintasa de Tipo I/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo I/fisiología , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/fisiología , Nitritos/sangre , Nitritos/líquido cefalorraquídeo , Ratas WistarRESUMEN
The participation of opioids in the antinociceptive effect of electroacupuncture was evaluated in terms of nociception produced by thermal stimuli applied to the face of male Wistar rats, weighing 180-230 g. Electrical stimulation (bipolar and asymmetric square wave with 0.5 mA intensity for 20 min) of acupoint St36, located in the anterior tibial muscle 10 mm distal to the knee joint, induced antinociception in the present model, which was maintained for 150 min. Acupoint LI4, located in the junction of the first and second metacarpal bones, did not achieve antinociception at any frequency studied (5 Hz: 1.7 +/- 0.1; 30 Hz: 1.8 +/- 0.1; 100 Hz: 1.7 +/- 0.1 vs 1.4 +/- 0.2). The antinociception obtained by stimulation of acupoint St36 was only achieved when high frequency 100 Hz (3.0 +/- 0.2 vs 1.0 +/- 0.1) was used, and not with 5 or 30 Hz (1.2 +/- 0.2 and 0.7 +/- 0.1 vs 1.0 +/- 0.1). The antinociceptive effect of acupuncture occurred by opioid pathway activation, since naloxone (1 and 2 mg/kg, subcutaneously) antagonized it (1.8 +/- 0.2 and 1.7 +/- 0.2 vs 3.0 +/- 0.1).
Asunto(s)
Analgesia por Acupuntura/métodos , Puntos de Acupuntura , Electroacupuntura , Dolor Facial/terapia , Receptores Opioides/fisiología , Animales , Masculino , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Dimensión del Dolor , Umbral del Dolor , Ratas , Ratas Wistar , Receptores Opioides/efectos de los fármacosRESUMEN
The participation of opioids in the antinociceptive effect of electroacupuncture was evaluated in terms of nociception produced by thermal stimuli applied to the face of male Wistar rats, weighing 180-230 g. Electrical stimulation (bipolar and asymmetric square wave with 0.5 mA intensity for 20 min) of acupoint St36, located in the anterior tibial muscle 10 mm distal to the knee joint, induced antinociception in the present model, which was maintained for 150 min. Acupoint LI4, located in the junction of the first and second metacarpal bones, did not achieve antinociception at any frequency studied (5 Hz: 1.7 ± 0.1; 30 Hz: 1.8 ± 0.1; 100 Hz: 1.7 ± 0.1 vs 1.4 ± 0.2). The antinociception obtained by stimulation of acupoint St36 was only achieved when high frequency 100 Hz (3.0 ± 0.2 vs 1.0 ± 0.1) was used, and not with 5 or 30 Hz (1.2 ± 0.2 and 0.7 ± 0.1 vs 1.0 ± 0.1). The antinociceptive effect of acupuncture occurred by opioid pathway activation, since naloxone (1 and 2 mg/kg, subcutaneously) antagonized it (1.8 ± 0.2 and 1.7 ± 0.2 vs 3.0 ± 0.1).
Asunto(s)
Animales , Masculino , Ratas , Puntos de Acupuntura , Analgesia por Acupuntura/métodos , Electroacupuntura , Dolor Facial/terapia , Receptores Opioides/fisiología , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Dimensión del Dolor , Umbral del Dolor , Ratas Wistar , Receptores Opioides/efectos de los fármacosRESUMEN
Davilla elliptica St Hill (Dilleniaceae) is widely used for multiple purposes in Brazil. The aim of this study was to verify the pharmacological support of this folk use and evaluate its use as antinociceptive. The hydroalcoholic extract of the stems (100-1000 mg/kg, p.o.) induced reduction of response in the formalin test inflammatory phase in mice. This antinociceptive effect does not involve the opioidergic pathway since it was not reverted by pre-treatment with naloxone nor due to myorelaxant activity since it did not affect rota-rod and tail-flick performance. Our results indicate a participation of the nitrergic pathway and may be of particular potential importance in clinical medicine, in view of the current interest in the assessment of new medicines originated from plants.
Asunto(s)
Analgésicos/farmacología , Dilleniaceae/química , Extractos Vegetales/farmacología , Administración Oral , Animales , Arginina/farmacología , Conducta Animal/efectos de los fármacos , Brasil , Inhibidores de la Ciclooxigenasa/administración & dosificación , Inhibidores de la Ciclooxigenasa/farmacología , Diclofenaco/administración & dosificación , Diclofenaco/farmacología , Inhibidores Enzimáticos/farmacología , Etanol/química , Formaldehído/administración & dosificación , Formaldehído/toxicidad , Miembro Posterior , Masculino , Medicina Tradicional , Ratones , NG-Nitroarginina Metil Éster/farmacología , Dolor/inducido químicamente , Dolor/prevención & control , Dimensión del Dolor/métodos , Componentes Aéreos de las Plantas/química , Extractos Vegetales/química , Agua/químicaRESUMEN
Solanum lycocarpum St. Hill (SL) is commonly used in Brazilian folk medicine. The aim of the present study was to evaluate the validity of the traditional therapeutic indication of SL as hypoglycaemic agent. The extract reduced glycemia to 92.4mg/dl in alloxan induced diabetic rats (230.5mg/dl). We also investigated the potential of SL as antioxidant (it reduced in 27% nitrate generation in diabetic animals). Our results also demonstrated that SL is not ulcerogenic and restored haemoglobin and haematocrit to normal values in diabetic animals.
Asunto(s)
Antioxidantes/farmacología , Diabetes Mellitus Experimental/prevención & control , Hipoglucemiantes/farmacología , Fitoterapia , Extractos Vegetales/farmacología , Solanum , Aloxano , Animales , Antioxidantes/administración & dosificación , Antioxidantes/uso terapéutico , Glucemia/efectos de los fármacos , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/inducido químicamente , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Masculino , Nitratos/sangre , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Ratas , Ratas WistarRESUMEN
Panax ginseng C.A. Meyer, the root of an Araliaceae plant has been shown to possess various biological effects. Ginseng treatment (100 mg kg(-1)) protected muscles from eccentric exercise injuries. It was effective in preserving mitochondrial membrane integrity and reduced nitrate concentration in vastus and rectus (46% and 26%, respectively). It also reduced carbonyl contents by approximately 27% in all the muscles studied.
Asunto(s)
Músculo Esquelético/efectos de los fármacos , Óxido Nítrico/biosíntesis , Panax , Condicionamiento Físico Animal/efectos adversos , Extractos Vegetales/farmacología , Animales , Masculino , Mitocondrias Musculares/efectos de los fármacos , Mitocondrias Musculares/metabolismo , Proteínas Musculares/efectos de los fármacos , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas , Ratas , Ratas WistarRESUMEN
Enzymatic activity was analyzed in the soleus, gastrocnemius (red and white) and plantaris muscles of acutely exercised rats after long-term administration of Panax ginseng extract in order to evaluate the protective role of ginseng against skeletal muscle oxidation. Ginseng extract (3, 10, 100, or 500 mg/kg) was administered orally for three months to male Wistar rats weighing 200 ± 50 g before exercise and to non-exercised rats (N = 8/group). The results showed a membrane stabilizing capacity of the extract since mitochondrial function measured on the basis of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase activities was reduced, on average, by 20 percent (P < 0.05) after exercise but the activities remained unchanged in animals treated with a ginseng dose of 100 mg/kg. Glutathione status did not show significant changes after exercise or treatment. Lipid peroxidation, measured on the basis of malondialdehyde levels, was significantly higher in all muscles after exercise, and again was reduced by about 74 percent (P < 0.05) by the use of ginseng extract. The administration of ginseng extract was able to protect muscle from exercise-induced oxidative stress irrespective of fiber type.
Asunto(s)
Animales , Masculino , Ratas , Antioxidantes/farmacología , Peroxidación de Lípido/efectos de los fármacos , Mitocondrias Musculares/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Condicionamiento Físico Animal , Panax/química , /metabolismo , Antioxidantes/administración & dosificación , Citrato (si)-Sintasa/metabolismo , Glutatión/efectos de los fármacos , Glutatión/metabolismo , Malondialdehído/análisis , Mitocondrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Extractos Vegetales/farmacología , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
Enzymatic activity was analyzed in the soleus, gastrocnemius (red and white) and plantaris muscles of acutely exercised rats after long-term administration of Panax ginseng extract in order to evaluate the protective role of ginseng against skeletal muscle oxidation. Ginseng extract (3, 10, 100, or 500 mg/kg) was administered orally for three months to male Wistar rats weighing 200 +/- 50 g before exercise and to non-exercised rats (N = 8/group). The results showed a membrane stabilizing capacity of the extract since mitochondrial function measured on the basis of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase activities was reduced, on average, by 20% (P < 0.05) after exercise but the activities remained unchanged in animals treated with a ginseng dose of 100 mg/kg. Glutathione status did not show significant changes after exercise or treatment. Lipid peroxidation, measured on the basis of malondialdehyde levels, was significantly higher in all muscles after exercise, and again was reduced by about 74% (P < 0.05) by the use of ginseng extract. The administration of ginseng extract was able to protect muscle from exercise-induced oxidative stress irrespective of fiber type.
Asunto(s)
Antioxidantes/farmacología , Peroxidación de Lípido/efectos de los fármacos , Mitocondrias Musculares/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Panax/química , Condicionamiento Físico Animal , 3-Hidroxiacil-CoA Deshidrogenasas/metabolismo , Animales , Antioxidantes/administración & dosificación , Citrato (si)-Sintasa/metabolismo , Glutatión/efectos de los fármacos , Glutatión/metabolismo , Masculino , Malondialdehído/análisis , Mitocondrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
Eccentric muscle contraction causes fibre injury associated with disruption of the myofibrillar cytoskeleton. The medicinal plant Panax ginseng C.A. Meyer, known for its therapeutic properties, was studied to explore its protective effects after eccentric contraction. A crude extract and a standardised extract (G115) of different saponin compositions were tested as to their efficacy in reducing lipid peroxidation, inflammation and release of myocellular proteins after the realisation of an eccentric contraction protocol on a rat treadmill. Plasma creatine kinase (CK) levels were significantly reduced by approximately 25% after ingestion of both extracts of ginseng. Both extracts reduced lipid peroxidation by approximately 15% as measured by malondialdehyde levels. beta-Glucuronidase concentrations and glucose-6-phosphate dehydrogenase (G6PDH) levels, which can be considered markers of inflammation, were also significantly reduced. The values of beta-glucuronidase were increased from 35.9+/-1.5 to 128.4+/-8.1 in vastus and to 131.1+/-12.1 U x g(-1) in rectus, the protection due to ginseng administration being approximately 40% in both muscles. Both extracts appeared to be equally effective in reducing injuries and inflammation caused by eccentric muscle contractions.