RESUMO
BACKGROUND AND OBJECTIVES: Micronutrient deficiencies are common among bariatric patients; this study aimed to determine whether a cognitive dissonance-based virtual program improved adherence to multivitamin use in bariatric patients from northern Mexico. METHODS AND STUDY DESIGN: A randomized controlled trial of the supplementation strategy was conducted over three months. The participants were randomized to an intervention or waitlisted control group and received two psycho-educative and four cognitive dissonance virtual sessions. Multiple linear regression was used to determine standardized estimates of associations between the intervention and dependent variables. Two path analyses were evaluated considering baseline and post-test measurements. RESULTS: Intervention was associated with higher concentrations of Hb (ß=0.758, p<0.001), vitamin D (ß=0.577, p<0.001), iron (ß=0.523, p<0.001), folate (ß=0.494, p<0.01), calcium (ß=0.452, p<0.01), higher adherence (ß=0.467, p<0.001), and level of knowledge (ß=0.298, p<0.05. CONCLUSIONS: The dissonance-based intervention potentiated the level of supplementation adherence. A higher level of adherence was reflected in micronutrient concentrations, thus providing confirmation of intervention. Thus, support is found for a multidisciplinary clinical practice that enhances nutrition status after bariatric surgery for obesity.
Assuntos
Cirurgia Bariátrica , Obesidade Mórbida , Dissonância Cognitiva , Suplementos Nutricionais , Ácido Fólico , Humanos , Micronutrientes , VitaminasRESUMO
A decoction prepared from the aerial parts of Melampodium divaricatum showed antinociceptive and antihyperalgesic responses when tested in the formalin model in mice. From the CH2 Cl2 fraction of the decoction, two non-previously reported secondary metabolites, 3-O-ß-D-glucopyranosyl-16α-hydroxy-ent-kauraneâ (1) and melampodiamideâ (2) [(2'R*,4'Z)-2'-hydroxy-N-[(2S*,3S*,4R*)-1,3,4-trihydroxyoctadec-2-yl]tetracos-4-enamide] were separated and characterized by spectroscopic, spectrometric, and computational techniques. The flavonoids isoquercitrin and hyperoside, which possessed noted antinociceptive properties, were obtained from the active AcOEt fraction of the decoction. The chemical composition of the essential oil of the plant was also analyzed by gas chromatography-mass spectrometry. The major constituents were (E)-caryophyllene, germacreneâ D, ß-elemene, δ-elemene, γ-patchoulene, and 7-epi-α-selinene. Headspace solid-phase microextraction analysis detected (E)-caryophyllene as the main volatile compound of the plant.
Assuntos
Analgésicos/química , Asteraceae/química , Óleos Voláteis/química , Extratos Vegetais/química , Analgésicos/isolamento & purificação , Analgésicos/uso terapêutico , Animais , Asteraceae/metabolismo , Diterpenos do Tipo Caurano/química , Diterpenos do Tipo Caurano/isolamento & purificação , Diterpenos do Tipo Caurano/uso terapêutico , Cromatografia Gasosa-Espectrometria de Massas , Masculino , Camundongos , Camundongos Endogâmicos ICR , Conformação Molecular , Neuralgia/induzido quimicamente , Neuralgia/tratamento farmacológico , Neuralgia/patologia , Componentes Aéreos da Planta/química , Componentes Aéreos da Planta/metabolismo , Extratos Vegetais/uso terapêutico , Microextração em Fase Sólida , EstereoisomerismoRESUMO
Breast cancer can be classified into molecular subtypes. Tumors overexpressing HER2 protein are more aggressive and metastatic; hence, patients have a poor prognosis. Anti-HER2 strategies, such as the monoclonal antibody Trastuzumab (Tz), have therefore been developed. Despite this progress, not all patients respond to the treatment. Retinoic acid (RA) has been proposed as an adjuvant treatment of breast carcinoma because of its ability to inhibit cell growth. We evaluated the effect of Tz in combination with RA on the viability, adhesion, migration, invasion and expression of migration-related proteins in SKBR3 and BT-474 human breast cancer cells. MTT, pharmacological interaction analysis, immunofluorescence, adhesion/migration/invasion and Western blot assays were performed. The coadministration of both drugs synergistically decreased cell survival. Tz+RA significantly decreased adhesion/migration/invasion in both cell types. Tz+RA strongly reduced FAK and HER2 expression and induced nuclear FAK translocation. In addition, a granular distribution of HER2 receptor was observed after the combined treatment. In conclusion, the coadministration of both drugs in patients with this type of cancer could contribute to the improvement of their prognosis and reduce the adverse effects of therapy because the applied Tz doses would be lower due to the adjuvant effect of RA.
RESUMO
The aim of this work was to design, synthesize and characterize the potential anti-nociceptive and anti-inflammatory activities of a new series of bioisosteres and hybrids from known non-steroidal anti-inflammatory drugs (NSAIDs). The compounds 4-(acetylamino)phenyl (2S)-2-(6-methoxy-2-naphthyl)propanoate (GUF-1) and 4-(acetylamino)phenyl 2-(R,S)-(4-isobutylphenyl)propanoate (GUF-2) were synthesized as hybrids (also known as heterodimers); whereas those named 2-(R,S)-(4-isobutylphenyl)-N-1H-tetrazol-5-ylpropanamide (GUF-3), (2S)-2-(6-methoxy-2-naphthyl)-N-1H-tetrazol-5-ylpropanamide (GUF-4), [2-(R,S)-N-hydroxy-2-[4-(2-methylpropyl)phenyl]propanamide] (GUF-5), and (2S)-N-hydroxy-2-(6-methoxy-2-naphthyl)propanamide (GUF-6) were synthesized as bioisosteres of the NSAIDs paracetamol, ibuprofen, and naproxen, respectively. All these compounds were characterized by spectroscopic and spectrometric analysis. Antinociceptive activity of GUF-1 to GUF-6 was evaluated using the formalin test in rats. Pharmacological responses of GUF-1, GUF-2 (hybrids), and GUF-5 (bioisostere) demonstrated significant antinociceptive effects; thus these compounds were assayed in an inflammation test like carrageenan-induced paw oedema in rats. Complete molecular docking of cyclooxygenase and the GUF-1 and GUF-2 hybrids showed high docking scores, compared to the reference drugs. Our data demonstrate that compounds GUF-1, GUF-2, and GUF-5 possesses antinociceptive and antiinflammatory activities resembling and improving those known for the traditional NSAIDs, paracetamol, naproxen and ibuprofen.
Assuntos
Acetaminofen/síntese química , Anti-Inflamatórios não Esteroides/síntese química , Ibuprofeno/síntese química , Simulação de Acoplamento Molecular/métodos , Naproxeno/síntese química , Medição da Dor/efeitos dos fármacos , Acetaminofen/metabolismo , Acetaminofen/farmacologia , Animais , Anti-Inflamatórios não Esteroides/metabolismo , Anti-Inflamatórios não Esteroides/farmacologia , Sítios de Ligação/fisiologia , Inibidores de Ciclo-Oxigenase/síntese química , Inibidores de Ciclo-Oxigenase/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Ibuprofeno/metabolismo , Ibuprofeno/farmacologia , Imageamento Tridimensional/métodos , Naproxeno/metabolismo , Naproxeno/farmacologia , Medição da Dor/métodos , Ratos , Ratos WistarRESUMO
The purpose of this research was to examine the preclinical efficacy of a decoction from the roots of Acourtia thurberi as a hypoglycemic, antihyperglycemic, and antihyperalgesic agent using well-known experimental models in mice. Acute oral administration of A. thurberi decoction did not produce toxic effects in mice, according to the Lorke procedure. A. thurberi decoction (31.6-316.2 mg/kg, p.âo.) decreased blood glucose levels during acute hypoglycemic and the oral glucose tolerance and oral sucrose tolerance tests, both in normoglycemic and hyperglycemic animals. Phytochemical analysis of A. thurberi roots led to the isolation of perezone (1), a mixture of α-pipitzol (2) and ß-pipitzol (3), and 8-ß-D-glucopyranosyloxy-4-methoxy-5-methyl-coumarin (4). A pharmacological evaluation of compounds 1-4 (3.2-31.6 mg/kg) using the same assays revealed their hypoglycemic and antihyperglycemic actions. Finally, local administration of A. thurberi decoction (31.6-316.2 µg/paw) and compounds 1-4 (3.2-31.6 µg/paw) produced significant inhibition on the licking time during the formalin test in healthy and hyperglycemic mice, demonstrating their antinociceptive and antihyperalgesic potential, respectively. Altogether, these results could be related to the use of A. thurberi for treating diabetes and painful complaints in contemporary Mexican folk medicine. A suitable UPLC-ESI/MS method was developed and successfully applied to quantify simultaneously compounds 1 and 4 in A. thurberi decoction.
Assuntos
Asteraceae/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/induzido quimicamente , Modelos Animais de Doenças , Humanos , Masculino , Medicina Tradicional , México , Camundongos , Camundongos Endogâmicos ICR , Niacinamida/efeitos adversos , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Estreptozocina/efeitos adversosRESUMO
Benzomalvin A (1), quinolactacins A1 (2), A2 (3) and B (4), quinolonimide (5), asperphenamate (6), and a new halogenated polyhydroxyanthraquinone, namely 2-chloro-6-[2'(S)-hydroxypropyl]-1,3,8-trihydroxy-anthraquinone (7), were isolated from an organic extract obtained from the solid culture of Penicillium spathulatum B35. Compounds 2 and 3 were isolated as an epimeric mixture, and compound 4 as a racemate. The structure of 7 was elucidated using 1D and 2D NMR, combined with computational methods (density functional theory). Compound 1, the mixture of 2 and 3, racemate 4, and compound 6 inhibited the yeast α-glucosidase in a concentration-dependent fashion with IC50 values of 383.2, 273.3, 57.3, and 8.3 µM, respectively. The α-glucosidase inhibitory properties of 1 were confirmed in vivo with an oral sucrose tolerance test in normal and hyperglycemic mice (p < 0.05). Furthermore, docking studies predicted that the most stable conformers of 1 bind to yeast and mammalian α-glucosidases with a higher affinity than acarbose. Finally, 1 also showed antihyperalgesic activity when tested in the formalin assay in hyperglycemic mice (p < 0.05).
Assuntos
Alcaloides/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Penicillium/química , alfa-Glucosidases/metabolismo , Alcaloides/química , Alcaloides/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Masculino , Camundongos Endogâmicos ICR , Modelos Moleculares , Estrutura MolecularRESUMO
O presente trabalho tem como objetivo discutir a importância do terapeuta infantil manter dentro de si uma visão binocular, que priorize tanto a escuta do mundo interno de seu pequeno paciente, mas também as interferências do inconsciente familiar e materno na sintomatologia infantil e no setting analítico. Partindo da perspectiva de que o mundo interno do infance se constrói também, embora não somente, pela demanda inconsciente dos pais, será ainda propósito deste artigo demonstrar como, neste caso clínico, a sintomatologia da criança foi influenciada por conflitivas inconscientes maternas e pela modalidade de cuidado parental presente nesta família.(AU)
This study aims to discuss the importance for a child therapist to keep a binocular vision which both prioritizes listening to the inner world of his/her little patient and the interferences of the family and maternal unconscious in the child symptomatology and in the analytic setting. From the perspective that the infant's inner world is also, although not only, built by the parental unconscious demand, the further purpose of this study is to demonstrate how, in this clinical case, the symptoms of the child were influenced by maternal unconscious conflicts and by the parental care modality existing in such family.(AU)
El presente trabajo tiene como objetivo discutir la importancia del terapeuta infantil mantener dentro de si una visión binocular que priorice tanto la escucha del mundo interno de su pequeño paciente, pero también las interferencias del inconsciente familiar y materno en la sintomatología infantil en el setting analítico. Partiendo de la perspectiva de que el mundo interno del infante se construye también, aunque no solamente, por la demanda inconsciente de los padres, va a ser todavía propósito de este artículo demonstrar cómo, en este caso clínico, la sintomatología del niño ha sido influenciada por conflictivas inconscientes maternas y por la modalidad de cuidado parental presente en esta familia.(AU)
Assuntos
Ludoterapia , Psicologia da Criança , Relações FamiliaresRESUMO
O presente trabalho tem como objetivo discutir a importância do terapeuta infantil manter dentro de si uma visão binocular, que priorize tanto a escuta do mundo interno de seu pequeno paciente, mas também as interferências do inconsciente familiar e materno na sintomatologia infantil e no setting analítico. Partindo da perspectiva de que o mundo interno do infance se constrói também, embora não somente, pela demanda inconsciente dos pais, será ainda propósito deste artigo demonstrar como, neste caso clínico, a sintomatologia da criança foi influenciada por conflitivas inconscientes maternas e pela modalidade de cuidado parental presente nesta família...
This study aims to discuss the importance for a child therapist to keep a binocular vision which both prioritizes listening to the inner world of his/her little patient and the interferences of the family and maternal unconscious in the child symptomatology and in the analytic setting. From the perspective that the infant's inner world is also, although not only, built by the parental unconscious demand, the further purpose of this study is to demonstrate how, in this clinical case, the symptoms of the child were influenced by maternal unconscious conflicts and by the parental care modality existing in such family...
El presente trabajo tiene como objetivo discutir la importancia del terapeuta infantil mantener dentro de si una visión binocular que priorice tanto la escucha del mundo interno de su pequeño paciente, pero también las interferencias del inconsciente familiar y materno en la sintomatología infantil en el setting analítico. Partiendo de la perspectiva de que el mundo interno del infante se construye también, aunque no solamente, por la demanda inconsciente de los padres, va a ser todavía propósito de este artículo demonstrar cómo, en este caso clínico, la sintomatología del niño ha sido influenciada por conflictivas inconscientes maternas y por la modalidad de cuidado parental presente en esta familia...
Assuntos
Humanos , Relações Familiares , Ludoterapia , Psicologia da CriançaRESUMO
The aim of this study was to investigate the endogenous opioid participation in the antinociceptive effect of R. officinalis aerial parts in experimental models of visceral, inflammatory and gout arthritis nociception. Acid-acetic induced writhing and formalin tests as well as the pain-induced functional impairment model in the rat (PIFIR) assay were studied. Antinociceptive doses of R. officinalis via oral, alone and in presence of an opioid antagonist were evaluated in comparison to the reference analgesic drug tramadol (31.6 and 50mg/kg i.p., in mice and rats, respectively). The antinociceptive effect of R. officinalis at a 300mg/kg dosage was significantly reverted in presence of 1.0mg/ kg s.c. of naloxone in writhing and formalin tests. Concerning PIFIR model, significant antinociceptive response produced for 1000 and 3000mg/kg was not inhibited in presence of 1.0 or 3.16mg/kg, s.c. of naloxone. In the antinociceptive effect of tramadol, naloxone produced partial inhibition in all models tested. These results suggest that antinociceptive and anti-inflammatory activities of R. officinalis aerial parts involve endogenous opioids, but activation of these mediators depends on the experimental model and the physiological process of the induced nociception.
El objetivo de este estudio fue investigar la participación de los opioides endógenos en el efecto antinociceptivo producido por un extracto preparado con las partes aéreas de Rosmarinus officinalis en modelos experimentales de nocicepción visceral, inflamatoria y tipo artritis gotosa. Para la inducción de nocicepción visceral e inflamatoria se utilizaron los modelos de estiramiento abdominal "writhing" y de formalina intraplantar al 1 %, respectivamente, en ratones. A su vez, para la nocicepción de tipo artritis gotosa se utilizó el modelo de disfunción inducida por ácido úrico al 20% intraarticular en ratas conocido como PIFIR (por sus siglas en inglés). Dosis antinociceptivas de R. officinalis vía oral se evaluaron solas y en presencia del antagonista de opioides endógenos naloxona. Adicionalmente, dicho efecto se comparó con el fármaco analgésico de referencia tramadol (31.6 y 50mg/kg i.p., en ratones y ratas, respectivamente). El efecto antinociceptivo de R. officinalis significativo en la dosis de 300mg/kg se revirtió en presencia de 1mg/kg s.c. de naloxona en las pruebas de estiramiento abdominal y formalina. En cuanto al modelo PIFIR, la respuesta antinociceptiva producida por 1000 y 3000mg/kg no se inhibió en presencia de 1 o 3.16mg/kg, s.c. de naloxona. En el efecto de tramadol, opioide atípico, la naloxona produjo inhibición parcial de la respuesta antinociceptiva en todos los modelos probados. Los resultados sugieren que la actividad antinociceptiva producida por el extracto de las partes aéreas de R. officinalis involucra al sistema de opioides endógenos, pero la presencia de estos mediadores depende del tipo de estímulo y del proceso fisiológico involucrado en la nocicepción inducida.
RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Rosemary is a species used worldwide as a common spice, but also in folk medicine for their therapeutic properties against abdominal pain. The rationale of this study was to examine the involvement of triterpenes and to compare their effectiveness in the antinociceptive effect of an ethanol extract of Rosmarinus officinalis L. (Lamiaceae). MATERIAL AND METHODS: Fractionation and HPLC analyses allowed the identification of a mixture of micromeric (121 mg/g), oleanolic (64 mg/g) and ursolic (83 mg/g) acids as partial antinociceptive responsible in an ethyl acetate fraction of R. officinalis by using the acetic acid-induced abdominal constrictions model in mice. RESULTS: These triterpenes individually evaluated produced a significant and dose-dependent antinociceptive response with similar potency as follows: ED50=1.1 mg/kg (0.9-1.3 mg/kg), 2.1 mg/kg (1.6-2.6 mg/kg) and 1.6 mg/kg (1.1-2.1 mg/kg), respectively, by using the intraperitoneal (i.p.) route of administration in mice. Their maximal antinociceptive efficacy resembled that produced by ketorolac (10 mg/kg, i.p.), a common clinic analgesic. CONCLUSION: Our results provide evidence that these triterpenes participate in the antinociceptive activity of R. officinalis. In addition, each individual triterpene showed a similar potency to that observed with ketorolac, a non-steroidal anti-inflammatory drug, in this experimental model.
Assuntos
Dor Abdominal/tratamento farmacológico , Analgésicos/uso terapêutico , Extratos Vegetais/uso terapêutico , Rosmarinus , Triterpenos/uso terapêutico , Dor Abdominal/induzido quimicamente , Dor Abdominal/fisiopatologia , Ácido Acético , Analgésicos/análise , Animais , Masculino , Camundongos , Nociceptividade/efeitos dos fármacos , Fitoterapia , Componentes Aéreos da Planta/química , Extratos Vegetais/análise , Plantas Medicinais , Triterpenos/análiseRESUMO
Hesperidin occurs in greatest concentration in plants from the Rutaceae and Lamiaceae families. In human nutrition it contributes to the integrity of blood vessels and its deficiency in the diet has been linked to abnormal capillary leakiness as well as pain. In this study, the bioflavonoid hesperidin was identified as an active compound in an ethanol extract of the Rosmarinus officinalis aerial parts tested in the pain-induced functional impairment model in the rat (PIFIR) as an assay of inflammatory and chronic nociception similar to that observed in clinical gout. Hesperidin produced a dose-dependent and significant response with an ED25=1666.72 mg/kg in comparison to an ED25=302.90 mg/kg for the extract or an ED25=0.47 mg/kg for the reference drug ketorolac in the PIFIR model. Although the antinociceptive response of R. officinalis was reverted in presence of the opioid antagonist naloxone (10 mg/kg, s.c.) and the 5HT(1A) antagonist WAY100635 (0.12 mg/kg, s.c.), the hesperidin response was not modified by naloxone (10 mg/kg), WAY100635 (0.12 mg/kg), bicuculline (1 mg/kg, s.c.), flumazenil (10 mg/kg, i.p.) or caffeine (1 mg/kg, s.c.). Nevertheless, it was reduced in presence of capsazepine (10 or 20 mg/kg, s.c.) suggesting the participation of the TRPV1 receptor, which was reinforced when hesperidin significantly reduced the capsaicin-induced nociceptive response. A synergistic interaction was also observed when antinociceptive doses of hesperidin were combined with those of ketorolac producing 15 combinations mainly in additive and supra-additive responses. These results provide evidence for the antinociceptive activity of hesperidin and demonstrate synergistic response when combined with ketorolac, possibly by involvement of the TRPV1 receptor, suggesting their clinical potential in pain therapy.
Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Gota/tratamento farmacológico , Hesperidina/uso terapêutico , Cetorolaco/uso terapêutico , Dor/tratamento farmacológico , Animais , Capsaicina/farmacologia , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Masculino , Dor/induzido quimicamente , RatosRESUMO
Annonas are consumed as fresh fruits, but are also widely used in folk medicine for treating pain and other ailments. Antinociceptive properties of the Annona diversifolia ethanol crude extract were tested using the pain-induced functional impairment model in rat (PIFIR) and the writhing test in mice. The ethanol extract caused a 25% recovery of limb function in rats; this response was significant and dose-dependent. Furthermore, this extract produced a similar antinociceptive response (ED(50)=15.35 mg/kg) to that of the reference drug tramadol (ED(50)=12.42 mg/kg) when evaluated in the writhing test in mice. Bio-guided fractionation yielded hexane and acetone active fractions from which the presence of palmitone and flavonoids was respectively detected. Palmitone produced an antinociceptive response with an ED(50)=19.57 mg/kg in the writhing test. Antinociceptive responses from ethanol extract and tramadol were inhibited in the presence of either naloxone (1mg/kg, s.c.)--an antagonist of endogenous opioids--or WAY100635 (0.8 mg/kg, s.c.)--a 5-HT(1A) serotonin receptor antagonist. These results provide evidence that A. diversifolia possesses antinociceptive activity, giving support to their traditional use for treatment of spasmodic and arthritic pain. In addition, our results suggest the participation of endogenous opioids and 5-HT(1A) receptors in this antinociceptive response.
Assuntos
Analgésicos/farmacologia , Annona/química , Hidrocarbonetos/farmacologia , Cetonas/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Dose Letal Mediana , Camundongos , RatosRESUMO
AIM OF THE STUDY: Around the world, Tilia species have been used in traditional medicine for their properties as tranquilizer. Furthermore, Mexican species of Tilia have been grouped as Tilia americana var. mexicana, but their specific content in flavonoids is poorly described. In this study, inflorescences of Mexican Tilia were collected in three different regions of Mexico to compare their flavonoid content and anxiolytic-like response. MATERIALS AND METHODS: Flavonoid content was analyzed by using an HPLC-MS technique. For anxiolytic-like response, Tilia inflorescences extracts (from 10 to 300 mg/kg, i.p.) were tested in experimental models (open-field, hole-board and plus-maze tests, as well as sodium pentobarbital-induced hypnosis) in mice. RESULTS: HPLC-MS analysis revealed specific peaks of flavonoid composition demonstrating some differences in these compounds in flowers and bracts depending on the region of collection. No differences in the neuropharmacological activity among these samples of Tilia were found. Moreover, their effects were associated with quercetin and kaempferol glycosides. CONCLUSIONS: Dissimilarities in the flavonoid composition of Mexican Tilias might imply that these species must be re-classified in more than one species, not as a unique Tilia americana var. mexicana. Since quercetin and kaempferol aglycons demonstrated anxiolytic-like response and that no difference in the pharmacological evaluation was observed between these three Mexican Tilias, we suggest that this pharmacological effect of Tilia inflorescences involves these flavonoids occurrence independently of the kind of glycosides present in the samples reinforcing their use in traditional medicine in several regions of Mexico.
Assuntos
Ansiolíticos/análise , Ansiolíticos/farmacologia , Quempferóis/análise , Quempferóis/farmacologia , Quercetina/análise , Quercetina/farmacologia , Tilia/química , Animais , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Glicosídeos/análise , Glicosídeos/farmacologia , Hipnose Anestésica , Hipnóticos e Sedativos/análise , Hipnóticos e Sedativos/farmacologia , Inflorescência/química , Locomoção/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Medicina Tradicional , México , Camundongos , Pentobarbital/farmacologia , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Quercetina/análogos & derivados , Tempo de Reação/efeitos dos fármacos , Especificidade da Espécie , Espectrometria de Massas em TandemRESUMO
Tilia species are well known around the world for their properties in traditional medicine. Antinociceptive activity of hexane, methanol and aqueous extracts from Tilia americana var. mexicana inflorescences was evaluated in the pain-induced functional impairment model in rats (PIFIR). A preliminar 300 mg/kg dosage of aqueous extracts i.p., but not the same dose of methanol or hexane extract, produced an antinociceptive response in rats similar to that of tramadol (17.8 mg/kg i.p.). A dose-response curve from aqueous extract allowed the determination of ED(50) = 364.97 mg/kg in comparison to ED(50) = 10.35 mg/kg for tramadol in this model. A previous HPLC-DAD analysis corroborated by an HPLC-MS technique in this study demonstrated the flavonoid composition in this Tilia aqueous extract revealing the presence of glycosides mainly derived from quercetin. Thus, Tilia aqueous extract and quercetin were tested at 30 and/or 100 mg/kg dosages i.p. in the PIFIR and formalin models producing a significant and dose-dependent antinociceptive response resembling that produced by a total and a partial agonist of 5-HT(1A) receptors like 8-OH-DPAT (0.1 mg/kg, s.c.) and buspirone (5 mg/kg, i.p.), respectively. In all the treatments, antinociceptive response was inhibited in the presence of WAY 100635 (0.12 mg/kg, i.p.). Our results support the analgesic activity of T. americana var. mexicana inflorescences attributed by folk medicine; they also indicate that quercetin is partly responsible for this pharmacological activity that is likely mediated by serotonin 5-HT(1A) receptors.
Assuntos
Medição da Dor/métodos , Dor/tratamento farmacológico , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Quercetina/uso terapêutico , Tilia , Animais , Área Sob a Curva , Artrite/diagnóstico , Artrite/etiologia , Comportamento Animal/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão/métodos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Interações Medicamentosas , Masculino , Dor/etiologia , Piperazinas/farmacologia , Piridinas/farmacologia , Ratos , Ratos Wistar , Antagonistas da Serotonina/farmacologiaRESUMO
Tilia species have been used as anxiolytics for many years. In a previous study anxiolytic-like effects of a hexane extract of Tilia americana var. mexicana inflorescences were observed in experimental models in mice. To get additional insights into the neuroactive actions of this particular Tilia species, in this study we report a bioactivity guided-fractionation of the extract and separation by column chromatographic methods to isolate three fatty acids and a triterpene identified as beta-sitosterol as major constituents. Our results revealed that the crude extract at 10 and 30 mg/kg I. P. and some pooled fractions at the same dosages potentiated sodium pentobarbital-induced sleeping time and caused a significant increase in the time spent at the open-arm sides in the plus-maze test. A reduction in the exploratory behavioral pattern manifested as ambulatory activity, as well as head dipping and rearing tests was also observed. Further fractionation and purification yielded four major fractions containing fatty acids and beta-sitosterol as the active compounds. A dose-response curve of beta-sitosterol in the range 1 to 30 mg/kg doses indicated that this compound produced an anxiolytic-like action from 1 to 10 mg/kg and a sedative response when the dose was increased to 30 mg/kg, these effects resemble those produced by diazepam (0.1 mg/kg). Our results suggest that hexane extract of Tilia americana var. mexicana produces depressant actions on the central nervous system, at least in part, because of the presence of beta-sitosterol and some fatty acids that remain to be identified.
Assuntos
Ansiolíticos/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Fitoterapia , Sitosteroides/farmacologia , Sono/efeitos dos fármacos , Tilia , Animais , Ansiolíticos/administração & dosagem , Ansiolíticos/uso terapêutico , Relação Dose-Resposta a Droga , Ácidos Graxos/administração & dosagem , Ácidos Graxos/farmacologia , Ácidos Graxos/uso terapêutico , Injeções Intraperitoneais , Masculino , Camundongos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Sitosteroides/administração & dosagem , Sitosteroides/uso terapêuticoRESUMO
The aim of this study was to investigate the behavioral effects of palmitone in the anti-anxiety response in experimental models in mice. In the elevated plus-maze test, palmitone (0.3, 1, 3, 10 and 30 mg/kg, I. P.) lengthened, from 50 % to 199 %, the time spent in the open arm region of the maze at all doses tested, as compared to the vehicle group ( P < 0.001). In relation to the rearing activity in the exploratory cylinder, palmitone significantly modified ( P < 0.05), in a dose-dependent manner, this activity by decreasing the number of rearings with an effective dose value (ED (50)) and 95 % confidence limits (CL (50)) of 0.79 (0.23 - 2.68) mg/kg. In addition, in the hole-board test, nose-poking was also significantly decreased ( P < 0.01) in a dose-dependent fashion [ED (50) (CL (50)) = 9.07 (4.51 - 18.26) mg/kg]. Moreover, palmitone at any dose caused no change in motor activity nor disruption in traction performance. In contrast, diazepam, used as reference drug, produced an anxiolytic effect with a significant and dose-dependent decrease in motor coordination accompanied by disruption of the traction performance. Behavioral studies suggest an anti-anxiety effect produced by palmitone, but its neuropharmacological profile differs from that observed for benzodiazepines such as diazepam.