RESUMEN
OBJECTIVE: The aim of this study was to investigate the anti-inflammatory effects of the crude extract (CE), derived fraction, and isolated compounds from Calea pinnatifida leaves in a mouse model of pulmonary neutrophilia. METHODS: The CE and derived fractions, hexane, ethyl acetate, and methanol, were obtained from C. pinnatifida leaves. The compounds 3,5- and 4,5-di-O-E-caffeoylquinic acids were isolated from the EtOAc fraction using chromatography and were identified using infrared spectroscopic data and nuclear magnetic resonance (1H and 13C NMR). Leukocytes count, protein concentration of the exudate, myeloperoxidase (MPO) and adenosine deaminase (ADA), and nitrate/nitrite (NO x ), tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1ß), and interleukin-17A (IL-17A) levels were determined in the pleural fluid leakage after 4 h of pleurisy induction. We also analyzed the effects of isolated compounds on the phosphorylation of both p65 and p38 in the lung tissue. RESULTS: The CE, its fractions, and isolated compounds inhibited leukocyte activation, protein concentration of the exudate, and MPO, ADA, NO x , TNF-α, IL-1ß, and IL-17A levels. 3,5- and 4,5-di-O-E-caffeoylquinic acids also inhibited phosphorylation of both p65 and p38 (P < 0.05). CONCLUSION: This study demonstrated that C. pinnatifida presents important anti-inflammatory properties by inhibiting activated leukocytes and protein concentration of the exudate. These effects were related to the inhibition of proinflammatory mediators. The dicaffeoylquinic acids may be partially responsible for these anti-inflammatory properties through the inhibition of nuclear transcription factor kappa B and mitogen-activated protein kinase pathways.
Asunto(s)
Asteraceae/química , Inflamación/tratamiento farmacológico , Trastornos Leucocíticos/tratamiento farmacológico , Enfermedades Pulmonares/tratamiento farmacológico , Neutrófilos/efectos de los fármacos , Extractos Vegetales/farmacología , Adenosina Desaminasa/metabolismo , Animales , Antiinflamatorios/farmacología , Carragenina , Modelos Animales de Enfermedad , Femenino , Inflamación/inducido químicamente , Interleucina-17/metabolismo , Interleucina-1beta/metabolismo , Trastornos Leucocíticos/inducido químicamente , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Enfermedades Pulmonares/inducido químicamente , Ratones , Nitratos/química , Nitritos/química , Peroxidasa/metabolismo , Fosforilación , Pleuresia/tratamiento farmacológico , Ácido Quínico/análogos & derivados , Ácido Quínico/química , Factor de Transcripción ReIA/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Ilex paraguariensis is a native plant from Southern America, where it is used as a beverage. In traditional medicine, it is used to treat many diseases including inflammation. However, we do not yet know precisely how this effect occurs. We therefore evaluated its anti-inflammatory effect in a murine model of pleurisy. The standardized CE, BF and ARF fractions, Caf, Rut and CGA were able to reduce leukocyte migration, exudate concentration, MPO and ADA activities and NOx levels. Moreover, I. paraguariensis also inhibited the release of Th1/Th17 pro-inflammatory cytokines, while increasing IL-10 production and improving the histological architecture of inflamed lungs. In addition, its major compounds decreased p65 NF-κB phosphorylation. Based on our results, we can conclude that I. paraguariensis exerts its anti-inflammatory action by attenuating the Th1/Th17 polarization in this model. This fact suggests that the use of this plant as a beverage can protect against Th1/Th17 inflammatory diseases.