RESUMEN
This study evaluated the antinociceptive and anti-edema properties of fractions of Coriandrum sativum Linn. (Apiaceae/Umbelliferae) leaves in mice. Ethyl acetate fractions (FAc) were obtained from dichloromethane extracts prepared from dried C. sativum (CS) leaves and stems. The effects of different concentrations of FAc on mice were observed using the open-field test, formalin-, capsaicin-, and carrageenan-induced paw edema tests, and the acetic acid-induced abdominal writhing test. Results from the carrageenan-induced paw edema test were subjected to a linear regression analysis and data from other assays were subjected to the Kruskal-Wallis test (followed by the SNK post hoc test). Dihydrocoriandrin (34.5%), coriandrin (14.4%), vitamin E (4.6%), and stigmasterol (7.9%) were identified in FAc. The number of squares the mice crossed in the open field test was decreased by 100â¯mg/kg and 300â¯mg/kg FAc (i.p.). The administration of 30, 100, and 300â¯mg/kg FAc induced fewer abdominal writhes than the control. In the formalin test, neurogenic pain was reduced by 20â¯mg/kg morphine and 30 and 100â¯mg/kg FAc, but not 5â¯mg/kg dexamethasone or 10â¯mg/kg FAc. Formalin-induced inflammatory pain was decreased by morphine, dexamethasone, and 30 and 100â¯mg/kg FAc. Morphine and 30, 100, and 300â¯mg/kg FAc significantly decreased the reaction time during the capsaicin test. Dexamethasone reduced both early and later phases of carrageenan-induced edema. Both 30 and 300â¯mg/kg FAc induced less edema than the control throughout the experiment. FAc showed antinociceptive, anti-edema and anti-inflammatory properties and it may be considered as a potential phytotherapeutic agent in the future.
Asunto(s)
Acetatos/química , Coriandrum/química , Edema/tratamiento farmacológico , Nocicepción/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Administración Oral , Animales , Constricción Patológica , Edema/patología , Masculino , Ratones , Actividad Motora/efectos de los fármacos , Fitoterapia , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Tiempo de ReacciónRESUMEN
BACKGROUND: Artemisia annua L. has been used for many centuries in Chinese traditional medicine. Artemisinin, the active principle was first isolated and identified in the 1970s becoming the global back bone to the fight against malaria. Our research group previously developed an economic and ecological friendly process to obtain this compound. In the pursuit to also exploit the residue generated throughout the process we further evaluated the pharmacological potential of that extract. METHODS: The alcoholic crude extract after artemisinin precipitation maintained an enriched sesquiterpene lactones content with residue artemisinin (1.72%) and deoxyartemisinin (0.31%), used as chemical markers for this sample. This study evaluated the pharmacological potential of the enriched sesquiterpene lactone fraction (Lac-FR) on different nociceptive and inflammatory experimental animal models. Previous findings on the biological properties of lactones obtained from natural products permitted us to explore the antinociceptive activities of these compounds based on in vivo chemical-induced behavioral assays. RESULTS: The enriched sesquiterpene lactone fraction (Lac-FR) was administrated by intraperitoneal injection producing a relevant reduction in the reaction time of the animals in both phases of the formalin test, significantly reduced the sensitivity to mechanical allodynia stimulus, reduced the paw edema caused by carrageenan injection and promoted high antinociceptive activity in tail flick model suggesting relationship with the opioid system. Further studies are being undertaken to elucidate the active components involved with the antinociceptive activity as well as evaluation of synergy effect that is seen by combination of substances that is greater than would be expected from consideration of individual contributions. CONCLUSION: For the first time, results presented herein provided consistent data to support the potential use of these lactones for pain relief as revealed by chemical-induced nociception assays in mice.
Asunto(s)
Analgésicos/farmacología , Artemisia annua/química , Artemisininas/farmacología , Lactonas/farmacología , Nocicepción/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Conducta Animal/efectos de los fármacos , Carragenina , Edema/tratamiento farmacológico , Masculino , Ratones , Dolor/tratamiento farmacológico , Dimensión del Dolor , Ratas , Ratas WistarRESUMEN
Cycloeucalenone (1) and 24-oxo-31-norcycloartanone (2) obtained from Solanum cernuum Vell. were assayed to explore their pharmacologic roles. Previous studies showed that (2) has selective activity against lung tumor cell line (NCIH460) which expresses high levels of COX-2, suggesting its role in inflammatory process, and also a link between chronic inflammation and cancer-associated process. Dichloromethane crude extract (DCE) significantly reduced writhing and stretching induced by 0.8 % acetic acid at a dose of 100, 300, and 600 mg/kg, po; oral administration of different doses of (1) and (2) also displayed significant analgesic and anti-inflammatory effects in the writhing acetic acid test (p < 0.0001). Selected oral doses of both compounds (100 and 50 mg/kg) were assayed in the carrageenan-induced paw edema model. Compound (2) showed significant activity during the early phase (1.5-6 h) and also in the late phase (48 h) (p < 0.01). The anti-nociceptive activity observed for the compounds (1) and (2) and DCE was found to be related to the inhibition of different mediators involved in inflammation and nociceptive process. Both compounds decrease COX-2 protein expression, although only compound (2) reached a significant response (p < 0.05 vs control). However, in vitro Sirtuin 1 activity and TNF-α production in THP-1 macrophages were not affected.
Asunto(s)
Analgésicos/uso terapéutico , Antiinflamatorios/uso terapéutico , Fitosteroles/uso terapéutico , Extractos Vegetales/uso terapéutico , Solanum , Triterpenos/uso terapéutico , Analgésicos/aislamiento & purificación , Animales , Antiinflamatorios/aislamiento & purificación , Edema/tratamiento farmacológico , Edema/patología , Ratones , Ratones Endogámicos BALB C , Dolor/tratamiento farmacológico , Dolor/patología , Fitosteroles/química , Fitosteroles/aislamiento & purificación , Extractos Vegetales/aislamiento & purificación , Triterpenos/química , Triterpenos/aislamiento & purificaciónRESUMEN
INTRODUCTION: The pharmacological assessment of the factors for gastric protection of a test substance should involve experimental models that can determine the involvement of cytoprotective factors, as well as their influence on the secretion of hydrochloric acid. The original protocol of pylorus ligation in rats proposed by Shay et al. in 1945, still in use today, provides a latency time of 240 min without considering the effect of postoperative pain in the mechanisms of peptic ulcer. This paper proposes a modification of this experimental protocol by eliminating the pain throughout the postoperative period, as a refinement of the test with consequent improvement of the pharmacological response. METHODS: Adult male Wistar/Uni rats underwent surgical ligation of the pylorus and were kept anesthetized throughout the experimental period (4h) in contrast to the other experimental groups that followed the original protocol proposed by Shay et al., 1945. RESULTS: We were able to determine effective doses for a positive control, as well as of a variety of secretagogues in the new experimental protocol proposed. DISCUSSION: The suppression of post-surgical pain, through the use of anesthesia throughout the experimental period, brought several benefits for the study of gastric acid secretion, rendering a more homogeneous pharmacologic response in non-inbred animals, thus being an effective experimental procedure.
Asunto(s)
Dolor Postoperatorio/prevención & control , Píloro/cirugía , Úlcera Gástrica/inducido químicamente , Animales , Betanecol/farmacología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Ácido Gástrico/metabolismo , Mucosa Gástrica/metabolismo , Histamina/farmacología , Ligadura , Masculino , Dolor Postoperatorio/fisiopatología , Pentagastrina/farmacología , Ratas , Ratas Wistar , Sensibilidad y Especificidad , Estómago/efectos de los fármacos , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patología , Estrés Fisiológico/fisiologíaRESUMEN
Harmicine is a ß-carboline alkaloid isolated and identified as a major active compound present in many plant species and marine invertebrates. This alkaloid exhibits a wide spectrum of pharmacological activities, including antispasmodic, antipyretic, and anticancer properties. This report described the antinociceptive properties of harmicine by means of chemical experimental models in order to evaluate the use for pain relief. The results demonstrating the potential analgesic properties of harmicine administered intraperitoneally were shown with the writhing test, reducing writhes around 60% (1 mg/kg), and in the formalin test, where harmicine was more effective toward neurogenic (reducing reaction time around 60%, 1 mg/kg) than inflammatory (68% reduction, 10 mg/kg) pain responses. Furthermore, these effects may operate via vanilloid receptors as revealed by the capsaicin test (41% reduction, with 3 mg/kg), as well as via peripheral glutamate receptors as shown by the glutamate test (50% reduction, with 1 mg/kg). Moreover, the opioid antagonist naloxone hydrochloride did not interfere in the antinociceptive properties of harmicine in the writhing test, revealing that this effect may not have a relationship with the opioid systems. Concluding, this report highlights harmicine as a new candidate to be used as analgesic in the future. Therefore, further studies are being undertaken in order to understand the exact mechanisms involved with the antinociceptive properties of harmicine.
Asunto(s)
Analgésicos/uso terapéutico , Modelos Animales de Enfermedad , Alcaloides Indólicos/uso terapéutico , Inflamación Neurogénica/tratamiento farmacológico , Dimensión del Dolor/efectos de los fármacos , Dolor/tratamiento farmacológico , Analgésicos/farmacología , Animales , Capsaicina/toxicidad , Alcaloides Indólicos/farmacología , Masculino , Ratones , Inflamación Neurogénica/inducido químicamente , Inflamación Neurogénica/patología , Dolor/inducido químicamente , Dolor/patología , Dimensión del Dolor/métodos , Tiempo de Reacción/efectos de los fármacos , Tiempo de Reacción/fisiologíaRESUMEN
The crude alcoholic extracts obtained from Pterodon pubescens Benth. seeds are widely used in Brazilian folk medicine as anti-inflammatory, analgesic, anti-rheumatic tonics and depurative preparations. We previously demonstrated the antinociceptive activity on writhing capsaicin, glutamate, and hot-plate tests of two compounds isolated from P. pubescens: geranylgeraniol (C1) and 6α,7ß-dihydroxyvouacapan-17ß-oate methyl ester (C2). This work is a continuation of the previous study investigating the possible mechanisms of action for compounds C1 and C2, and the differences between them. The present study demonstrated that when administered intraperitoneally (i.p.): i), compounds C1 and C2 produced significant anti-allodynic activity during the acute phase of the Complete Freund's Adjuvant (CFA)-induced persistent pain model; ii) compound C1 produced significant anti-hypernociception activity in the carrageenan-induced pain model; iii) compound C2 presented a significant loss of activity after p-chlorophenylalanine methyl ester hydrochloride (PCPA) [5-HT synthesis inhibitor] treatment, suggesting that the mechanisms of action could be related to either the synthesis or release of serotonin; iv) compound C1 presented a significant loss of activity after ondansetron (5-HT(3) receptor antagonist) treatment suggesting activity upon 5-HT(3) serotonin receptors; v) compound C1 presented a significant loss of activity after efaroxan (mixed I(1) imidazoline/α(2)-adrenoceptor antagonist) treatment suggesting the participation of this compound upon imidazoline I(1) receptors; and vi) both compounds C1 and C2 did not appear to exert their activity via 5-HT(1A), 5-HT(2A), imidazoline I(2), α(2)-adrenoceptor, nitric oxide, GABA(A), acetylcholine muscarinic, and nicotinic receptors when evaluated in acetic acid-induced nociception.
Asunto(s)
Analgésicos/aislamiento & purificación , Analgésicos/farmacología , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Fabaceae/química , Analgésicos/uso terapéutico , Animales , Diterpenos/uso terapéutico , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/metabolismo , Imidazolinas/metabolismo , Masculino , Ratones , Serotonina/metabolismoRESUMEN
BACKGROUND: Pterodon pubescens Benth seeds are commercially available in the Brazilian medicinal plant street market. The crude alcoholic extracts of this plant are used in folk medicine as anti-inflammatory, analgesic, and anti-rheumatic preparations. The aim of this study was to evaluate the contribution of geranylgeraniol (C1) and 6alpha, 7beta-dihydroxyvouacapan-17beta-oate methyl ester (C2) isolated from Pterodon pubescens Benth. to the antinociceptive activity of the crude extract. RESULTS: Compounds C1 and C2 demonstrated activity against writhing with intraperitoneal (i.p.) and oral (p.o.) routes, capsaicin (i.p. and p.o.), glutamate (i.p.), and in the hot-plate (p.o.) tests, demonstrating their contribution to the antinociceptive activity of crude Pterodon pubescens Benth extracts. The observed activity of compounds C1 and C2 may be related to vanilloid receptors VR1, and/or glutamate peripheral receptors. In hot-plate model, the antinociceptive activity was maintained when naloxone chloride (opioid antagonist) was administered prior to treatment with compounds suggesting that C1 and C2 (p.o.) do not exert their antinociceptive effects in the hot-plate test via opioid receptors. The findings presented herein also suggest that compounds within the crude Pterodon pubescens Benth. extract may exert a synergistic interactive effect, since the crude extract (300 mg x kg-1) containing lower concentrations of compounds C1 (11.5%- 34.6 mg x kg-1) and C2 (1.5% - 4.7 mg x kg-1) gave statistically the same effect to the pure compounds when tested separately (C1 = C2 = 300 mg.kg-1) in writhing experimental model with p.o. administration. Further studies will be undertaken to establish more specifically the mechanisms of action for compounds C1 and C2. Possible synergistic interactions will be evaluated employing the Isobole method. CONCLUSION: These results allowed us to establish a relationship between the popular use of Pterodon pubescens seeds for pain relief and the activity of two major compounds isolated from this species which demonstrated antinociceptive activity. Various "in vivo" experimental models corroborate the folk use of this species for different pain and inflammation disorders.
Asunto(s)
Analgésicos/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Diterpenos/uso terapéutico , Dolor/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Administración Oral , Animales , Brasil , Modelos Animales de Enfermedad , Diterpenos/química , Fabaceae/química , Medicina Tradicional , Dimensión del Dolor/efectos de los fármacos , Fitoterapia , Plantas Medicinales/química , Ratas , Ratas Sprague-Dawley , Semillas/química , Semillas/efectos de los fármacosRESUMEN
The present study examined the antinociceptive effects of agmatine in chemical behavioural models of pain. Agmatine (1-30 mg/kg), given by i.p. route, 30 min earlier, produced dose-dependent inhibition of acetic acid-induced visceral pain, with mean ID50 value of 5.6 mg/kg. Given orally, 60 min earlier, agmatine (10-300 mg/kg) also produced dose-related inhibition of the visceral pain caused by acetic acid, with mean ID50 value of 147.3 mg/kg. Agmatine (3-100 mg/kg, i.p.) also caused significant and dose-dependent inhibition of capsaicin- and glutamate-induced pain, with mean ID50 values of 43.7 and 19.5 mg/kg, respectively. Moreover, agmatine (1-100 mg/kg, i.p.) caused marked inhibition of both phases of formalin-induced pain, with mean ID50 values for the neurogenic and the inflammatory phases of 13.7 and 5.6 mg/kg, respectively. The antinociception caused by agmatine in the acetic acid test was significantly attenuated by i.p. treatment of mice with L-arginine (precursor of nitric oxide, 600 mg/kg), naloxone (opioid receptor antagonist, 1 mg/kg), p-chlorophenylalanine methyl ester (PCPA, an inhibitor of serotonin synthesis, 100 mg/kg once a day for 4 consecutive days), ketanserin (a 5-HT2A receptor antagonist, 0.3 mg/kg), ondansetron (a 5-HT3 receptor antagonist, 0.5 mg/kg), yohimbine (an alpha2-adrenoceptor antagonist, 0.15 mg/kg) or by efaroxan (an I1 imidazoline/alpha2-adrenoceptor antagonist, 1 mg/kg). In contrast, agmatine antinociception was not affected by i.p. treatment of animals with pindolol (a 5-HT1A/1B receptor antagonist, 1 mg/kg) or idazoxan (an I2 imidazoline/alpha2-adrenoceptor antagonist, 3 mg/kg). Likewise, the antinociception caused by agmatine was not affected by neonatal pre-treatment with capsaicin. Together, these results indicate that agmatine produces dose-related antinociception in several models of chemical pain through mechanisms that involve an interaction with opioid, serotonergic (i.e., through 5-HT2A and 5-HT3 receptors) and nitrergic systems, as well as via an interaction with alpha2-adrenoceptors and imidazoline I1 receptors.