RESUMO
Patient-reported outcome (PRO) measures provide an important perspective on how patients feel and function that cannot be adequately captured by clinical measures. A PRO is any report that comes directly from a patient about a health condition or its treatment without interpretation of the patient's response by a clinician or anyone else.
Assuntos
Aprovação de Equipamentos/normas , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Satisfação do Paciente , United States Food and Drug Administration/tendências , Aprovação de Drogas/métodos , Humanos , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e Questionários , Estados UnidosRESUMO
UNLABELLED: This study was designed to determine if the Amazonian medicinal sangre de grado, confers benefit by suppressing the activation of sensory afferent nerves. METHODS: (i) vasorelaxation of rat mesenteric arteries in response to calcitonin gene-related peptide; (ii) rat paw edema in response to protease- activating peptide receptor 2-activating peptide; (iii) rat paw hyperalgesia in response to low-dose protease-activating peptide receptor 2-activating peptide or prostaglandin E2; (iv) gastric hyperemia in response luminal capsaicin; (v) a clinical trial of a sangre de grado balm in pest control workers. The parent botanical was fractionated for evaluation of potential active components. In preconstricted rat mesenteric arteries, highly diluted sangre de grado (1:10,000) caused a shift to the right of the calcitonin gene-related peptide dose-response curve (p < 0.01). Paw edema in response to protease-activating peptide receptor 2-activating peptide (500 microg) was reduced by as single topical administration sangre de grado balm (1% concentration, p < 0.01) for at least 6 h. Hyperalgesia induced by either low-dose protease-activating peptide receptor 2-activating peptide (50 microg) or prostaglandin E2 was prevented by sangre de grado balm. A fraction possessing analgesic and capsaicin antagonistic properties was isolated and high-performance liquid chromatography and gas chromatography-mass spectrometry analysis indicated that it was a proanthocyandin oligomer. In pest control workers, sangre de grado balm (Zangrado) was preferred over placebo, for the relief of itching, pain, discomfort, edema, and redness in response to wasps, fire ants, mosquitoes, bees, cuts, abrasions, and plant reactions. Subjects reported relief within minutes. We conclude that sangre de grado is a potent inhibitor of sensory afferent nerve mechanisms and supports its ethnomedical use for disorders characterized by neurogenic inflammation.
Assuntos
Inflamação Neurogênica/tratamento farmacológico , Fitoterapia , Extratos Vegetais/farmacologia , Animais , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Capsaicina/farmacologia , Edema/tratamento farmacológico , Feminino , Humanos , Hiperemia/tratamento farmacológico , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/fisiopatologia , Inflamação Neurogênica/fisiopatologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Endogâmicos F344 , Receptor PAR-2 , Receptores de Trombina/agonistas , Estômago/fisiopatologia , Vasodilatação/efeitos dos fármacosRESUMO
Cat's claw (Uncaria tomentosa) is a medicinal plant from the Amazon River basin that is widely used for inflammatory disorders and was previously described as an inhibitor of NF-kappaB. Cat's claw was prepared as a decoction (water extraction) of micropulverized bark with and without concentration by freeze-drying. Murine macrophages (RAW 264.7 cells) were used in cytotoxicity assays (trypan blue exclusion) in response to the free radical 1, 1-diphenyl-2-picrilhydrazyl (DPPH, 0.3 microM) and ultraviolet light (UV) light. TNFalpha production was induced by lipopolysaccharide (LPS 0.5 microg/ml). Cat's claw was an effective scavenger of DPPH; the EC(50) value for freeze-dried concentrates was significantly less than micropulverized (18 vs. 150 microg/ml, p <.05). Cat's claw (10 microg/ml freeze-dried) was fully protective against DPPH and UV irradiation-induced cytotoxicity. LPS increased TNFalpha media levels from 3 to 97 ng/ml. Cat's claw suppressed TNFalpha production by approximately 65-85% (p <.01) but at concentrations considerably lower than its antioxidant activity: freeze-dried EC(50) = 1.2 ng/ml, micropulverized EC(50) = 28 ng/ml. In conclusion, cat's claw is an effective antioxidant, but perhaps more importantly a remarkably potent inhibitor of TNFalpha production. The primary mechanism for cat's claw anti-inflammatory actions appears to be immunomodulation via suppression of TNFalpha synthesis.
Assuntos
Antioxidantes/farmacologia , Unha-de-Gato , Sobrevivência Celular/efeitos dos fármacos , Sequestradores de Radicais Livres , Macrófagos/fisiologia , Picratos , Extratos Vegetais/farmacologia , Plantas Medicinais , Fator de Necrose Tumoral alfa/biossíntese , Animais , Bepridil/análogos & derivados , Bepridil/farmacologia , Compostos de Bifenilo , Morte Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos da radiação , Radicais Livres , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Camundongos , Caules de Planta , Raios UltravioletaRESUMO
Sangre de grado is an Amazonian herbal medicine used to facilitate the healing of gastric ulcers and to treat gastritis, diarrhea, skin lesions, and insect stings. This study was designed to evaluate the gastrointestinal applications. Gastric ulcers were induced in rats by brief serosal exposure of the fundus to acetic acid (80%). Sangre de grado was administered in drinking water at 1:1,000 and 1:10,000 dilutions from the postoperative period to day 7. Guinea pig ileum secretory responses to capsaicin, electrical field stimulation, and the neurokinin-1 (NK-1) agonist [Sar(9),Met(O(2))(11)]substance P were examined in Ussing chambers. Sangre de grado facilitated the healing of experimental gastric ulcer, reducing myeloperoxidase activity, ulcer size, and bacterial content of the ulcer. The expression of proinflammatory genes tumor necrosis factor-alpha, inducible nitric oxide synthase (iNOS), interleukin (IL)-1beta, IL-6, and cyclooxygenase-2 was upregulated by ulcer induction but reduced by sangre de grado treatment, particularly iNOS and IL-6. In Ussing chambers, sangre de grado impaired the secretory response to capsaicin but not to electrical field stimulation or the NK-1 agonist. We conclude that sangre de grado is a potent, cost-effective treatment for gastrointestinal ulcers and distress via antimicrobial, anti-inflammatory, and sensory afferent-dependent actions.