Assuntos
Abrasão Química/métodos , Óleo de Cróton/administração & dosagem , Ceratolíticos/administração & dosagem , Fenóis/administração & dosagem , Envelhecimento da Pele/efeitos dos fármacos , Óleo de Cróton/química , Método Duplo-Cego , Estabilidade de Medicamentos , Face , Feminino , Humanos , Ceratolíticos/química , Fenóis/química , Fotografação , Pele/diagnóstico por imagem , Pele/efeitos dos fármacos , Tensoativos/administração & dosagem , Tensoativos/química , Resultado do TratamentoRESUMO
Pain and inflammation are complex clinical conditions that are present in a wide variety of disorders. Most drugs used to treat pain and inflammation have potential side effects, which makes it necessary to search for new sources of bioactive molecules. In this paper, we describe the ability of LASSBio-1586, an N-acylhydrazone derivative, to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In these experimental models, LASSBio-1586 significantly (p<0.05) reduced nociceptive behavior. Several methods of acute and chronic inflammation induced by different chemical (carrageenan, histamine, croton oil, arachidonic acid) and physical (cotton pellet) agents were used to evaluate the anti-inflammatory effect of LASSBio-1586. LASSBio-1586 exhibited potent anti-inflammatory activity in all tests (p<0.05). Study of the mechanism of action demonstrated the possible involvement of the nitrergic, serotonergic and histamine signaling pathways. In addition, a molecular docking study was performed, indicating that LASSBio-1586 is able to block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. In summary, LASSBio-1586 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug.
Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Edema/tratamento farmacológico , Hidrazonas/farmacologia , Nociceptividade/efeitos dos fármacos , Dor Nociceptiva/tratamento farmacológico , Ácido Acético , Analgésicos/síntese química , Animais , Anti-Inflamatórios não Esteroides/síntese química , Ácido Araquidônico/administração & dosagem , Carragenina/administração & dosagem , Óleo de Cróton/administração & dosagem , Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/síntese química , Dexametasona/farmacologia , Modelos Animais de Doenças , Edema/induzido quimicamente , Edema/metabolismo , Edema/patologia , Formaldeído , Membro Posterior , Histamina/administração & dosagem , Hidrazonas/síntese química , Indometacina/farmacologia , Inflamação , Masculino , Camundongos , Simulação de Acoplamento Molecular , NG-Nitroarginina Metil Éster/farmacologia , Dor Nociceptiva/induzido quimicamente , Dor Nociceptiva/metabolismo , Dor Nociceptiva/fisiopatologia , Ondansetron/farmacologia , Prostaglandinas/biossínteseRESUMO
The present study evaluated the effect of the crude extract of the leaves of Nectandra falcifolia (NEES) Castiglioni and its fractions in different experimental models of inflammation (paw edema, pleurisy, and ear edema). Carrageenan-induced edema of the paw and pleurisy were evaluated in Wistar rats (180-220 g), which were treated with different doses of the total extract (250, 500 mg.kg-1). Edema of the ear, induced by croton oil, and determination of myeloperoxidase activity were evaluated in Swiss mice (25-35 g). In this experiment, the crude extract of Nectandra falcifolia (Nf) (1.25, 2.5, 5.0, 7.5 mg) and the hexane, chloroform, ethyl-acetate and hydromethanol fractions (5.0 mg) were applied topically, immediately after application of the oil. The crude extract of Nf (500 mg.kg-1) significantly reduced edema of the paw compared to the control group. Similarly, at doses of 250 and 500 mg.kg-1 it significantly reduced the volume of pleural inflammatory exudate compared to the control animals. However, it did not change the number of migrated cells. At doses of 2.5, 5.0 and 7.5 mg, the crude extract significantly inhibited edema of the ear and the influx of neutrophils. The fractions from Nectandra falcifolia (hexane, chloroform, ethyl acetate and hydromethanol) also inhibited edema of the ear. Taken together, the results demonstrated that the crude extract and its fractions administered to animals orally or topically showed an anti-inflammatory effect.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Lauraceae/química , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Carragenina/administração & dosagem , Carragenina/toxicidade , Óleo de Cróton/administração & dosagem , Óleo de Cróton/toxicidade , Avaliação Pré-Clínica de Medicamentos/métodos , Orelha/patologia , Edema/induzido quimicamente , Edema/metabolismo , Edema/prevenção & controle , Membro Posterior/efeitos dos fármacos , Membro Posterior/patologia , Indometacina/farmacologia , Indometacina/uso terapêutico , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/prevenção & controle , Injeções Intradérmicas , Masculino , Óxido Nítrico/metabolismo , Peroxidase/metabolismo , Fitoterapia/métodos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Pleurisia/induzido quimicamente , Pleurisia/metabolismo , Pleurisia/prevenção & controle , Ratos , Ratos Wistar , Solventes/químicaRESUMO
The essential oil of Croton zehntneri Pax et Hoffm. (EOCZ) contains anethole (42%) and estragole (46%), two isomers that share some chemical structural similarities with capsaicin. The present study investigated the cardiovascular effects of EOCZ and the role of capsaicin-sensitive sensory nerve fibres in the mediation of these effects in anaesthetized rats. 2. Intravenous bolus injection of EOCZ (1-20 mg/kg) elicited dose-dependent hypotension and bradycardia that were immediate and transient. Similar responses were also observed with anethole and estragole (both at 10 mg/kg). After cervical bivagotomy or perineural treatment of both cervical vagus nerves with capsaicin (250 mg/mL) to selectively block the conduction of sensory C-fibres, both cardiovascular responses to EOCZ (10 mg/kg) were abolished. 3. Like capsaicin, an epigastric retrograde intra-arterial injection of EOCZ (10 mg/kg, i.a.) into the femoral artery elicited a monophasic hypotensive response. This reflex response was blocked by either neonatal pretreatment with capsaicin (50 mg/kg, s.c.) or intrathecal injection of the substance P receptor antagonist RP 67580 (7.8 nmol, at the spinal level L5-L6), suggesting that it is mediated exclusively by substance P-containing primary afferent fibres. 4. The cardiovascular responses to EOCZ (10 mg/kg, i.v.) were also significantly reduced by the selective vallinoid TPRV1 receptor antagonist capsazepine (1 mg/kg, i.v.). 5. It is concluded that i.v. administration of EOCZ in anaesthetized rats elicits a capsaicin-like bradycardic and depressor reflex, which appears to be mediated by the activation of vallinoid TPRV1 receptors located on vagal sensory nerves. Like capsaicin, i.a. injection of EOCZ induces a spinally mediated sensory reflex.
Assuntos
Capsaicina/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Óleo de Cróton/farmacologia , Croton/química , Neurônios Aferentes/efeitos dos fármacos , Derivados de Alilbenzenos , Anestesia , Animais , Animais Recém-Nascidos , Anisóis/administração & dosagem , Anisóis/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Óleo de Cróton/administração & dosagem , Relação Dose-Resposta a Droga , Artéria Femoral , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Injeções Intra-Arteriais , Masculino , Fibras Nervosas Amielínicas/efeitos dos fármacos , Folhas de Planta/química , Ratos , Ratos Wistar , Canais de Cátion TRPV/efeitos dos fármacosRESUMO
Croton zehntneri is an aromatic plant native to Northeastern Brazil, where it is often used in folk medicine. In the present study the antinociceptive effects of the essential oil of Croton zehntneri (EOCz) were evaluated in mice. EOCz administered orally at doses of 100 and 300 mg/kg reduced paw licking time in the second phase of the formalin test from the control value of 41.61 + or - 8.62 to 12.01 + or - 7.97 and 6.57 + or - 3.42 s, respectively. During the first phase of the formalin test only 300 mg/kg induced a significant alteration (from 58.2 + or - 7.02, control, to 28.7 + or - 4.73 s). The number of contortions in response to intraperitoneal injections of acetic acid did not differ significantly between controls (80.6 + or - 9.01) and experimental (300 mg/kg body weight) animals (89.1 + or - 9.53 percent of the control numbers; P > or = 0.05, Student t-test). In the hot-plate test, EOCz at doses > or = 100 mg/kg significantly increased the latency time with respect to controls (11.2 + or - 0.80). At 100 and 300 mg/kg this increase persisted for 180 and 240 min, respectively. The data show that EOCz is effective as an antinociceptive agent
Assuntos
Animais , Masculino , Camundongos , Analgésicos/administração & dosagem , Óleo de Cróton/administração & dosagem , Dor , Administração Oral , Análise de Variância , Medição da Dor , Tempo de ReaçãoRESUMO
Croton zehntneri is an aromatic plant native to Northeastern Brazil, where it is often used in folk medicine. In the present study the antinociceptive effects of the essential oil of Croton zehntneri (EOCz) were evaluated in mice. EOCz administered orally at doses of 100 and 300 mg/kg reduced paw licking time in the second phase of the formalin test from the control value of 41.61 +/- 8.62 to 12.01 +/- 7.97 and 6.57 +/- 3.42 s, respectively. During the first phase of the formalin test only 300 mg/kg induced a significant alteration (from 58.2 +/- 7.02, control, to 28.7 +/- 4.73 s). The number of contortions in response to intraperitoneal injections of acetic acid did not differ significantly between controls (80.6 +/- 9.01) and experimental (300 mg/kg body weight) animals (89.1 +/- 9.53% of the control numbers; P > or =0.05, Student t-test). In the hot-plate test, EOCz at doses > or =100 mg/kg significantly increased the latency time with respect to controls (11.2 +/- 0.80). At 100 and 300 mg/kg this increase persisted for 180 and 240 min, respectively. The data show that EOCz is effective as an antinociceptive agent.
Assuntos
Analgésicos/administração & dosagem , Óleo de Cróton/administração & dosagem , Dor/tratamento farmacológico , Administração Oral , Análise de Variância , Animais , Avaliação Pré-Clínica de Medicamentos , Masculino , Camundongos , Medição da Dor , Tempo de ReaçãoRESUMO
Espécies do gênero Copaifera (Leguminosae) são nativas de regiões tropicais da América Latina e África. No Brasil, seu óleo-resina é amplamente utilizado em medicina popular como antiinflamatório, antisséptico e cicatrizante. No presente trabalho, avaliou-se, em uma primeira fase, a atividade antiinflamatória em modelo experimental agudo das seguintes amostras de óleo-resina: comercial, gentilmente cedida pela empresa Pronatus, Copaifera reticulata, C. multijuga e C. paupera. As amostras foram administradas pela via oral, sendo selecionada, das amostras identificadas botanicamente, a C. reticulata por apresentarem maior atividade. A amostra comercial também foi ensaiada no modelo experimental acima...
Assuntos
Animais , Ratos , Camundongos , Alcaloides/análise , Anti-Inflamatórios/uso terapêutico , Diterpenos/toxicidade , Medicina Herbária , Nistatina/administração & dosagem , Óleo de Cróton/administração & dosagem , Óleos de Plantas/química , Plantas Medicinais/toxicidade , Resinas/química , Sesquiterpenos/toxicidade , Cromatografia Gasosa , Espectrometria de Massas , Testes de ToxicidadeRESUMO
A sequential histologic, ultrastructural and immuno pathologic study was carried out in the Selye's inflammatory pouch model to observe extracellular matrix and cellular changes during granulation tissue formation. Besides changes involving different components of the connective tissue, it was observed that collagen resorption occurred under a biphasic process. At an early phase (3rd to 15th day), in which exudative inflammatory changes predominated, signs of collagen synthesis and degradation were seen simultaneously. Extracellular breakdown and internalization of collagen fragments within fibroblasts and myofibroblasts were observed. Later on (30th to 60th day), changes affecting collagen had a different ultrastructural appearance. Collagen fragmentation, focal "lytic" and "electron dense" changes occurred in the extracellular space specially at the periphery of fibroblasts, myofibroblasts and smooth muscle cells. Collagen degradation, thus seems to be a continuous process in granulation tissue, occurring with different morphologies at different times.
Assuntos
Colágeno/metabolismo , Tecido de Granulação/metabolismo , Animais , Óleo de Cróton/administração & dosagem , Matriz Extracelular/metabolismo , Matriz Extracelular/ultraestrutura , Feminino , Fibroblastos/metabolismo , Fibroblastos/ultraestrutura , Tecido de Granulação/citologia , Tecido de Granulação/ultraestrutura , Injeções Subcutâneas , Masculino , Microscopia Eletrônica , Músculo Liso/citologia , Músculo Liso/metabolismo , Músculo Liso/ultraestrutura , RatosRESUMO
O comportamento do gerbil (Meriones unguiculatus) como modelo em oncologia experimental é estudado. Aplicaçöes tópicas de 3-metilcolantreno (MC), sobre a pele do dorso, induziram pailomas, carcinomas epidermoides, carcinomas basocelulares e lesöes hiperpigmentadas semelhantes ao nevus azul. Ao contr rio, somente lesöes pigmentadas foram observadas nos animais tratados com MC (iniciaçäo) associado ao óleo de croton (promoçäo). Além disoo, fibrossarcomas e um linfoma foram induzidos com injeçöes subcutâneas de MC.