RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria tomentosa (Willd. Ex Schult) DC is used by indigenous tribes in the Amazonian region of Central and South America to treat inflammation, allergies and asthma. The therapeutic properties of U. tomentosa have been attributed to the presence of tetracyclic and pentacyclic oxindole alkaloids and to phenolic acids. AIMS OF THE STUDY: To characterize aqueous bark extracts (ABE) and aqueous leaf extracts (ALE) of U. tomentosa and to compare their anti-inflammatory effects. MATERIALS AND METHODS: Constituents of the extracts were identified by ultra performance liquid chromatography-mass spectrometry. Anti-inflammatory activities were assessed in vitro by exposing lipopolysaccharide-stimulated macrophage cells (RAW264.7-Luc) to ABE, ALE and standard mitraphylline. In vivo assays were performed using a murine model of ovalbumin (OVA)-induced asthma. OVA-sensitized animals were treated with ABE or ALE while controls received dexamethasone or saline solution. Bronchial hyperresponsiveness, production of Th1 and Th2 cytokines, total and differential counts of inflammatory cells in the bronchoalveolar lavage (BAL) and lung tissue were determined. RESULTS: Mitraphylline, isomitraphylline, chlorogenic acid and quinic acid were detected in both extracts, while isorhyncophylline and rutin were detected only in ALE. ABE, ALE and mitraphylline inhibited the transcription of nuclear factor kappa-B in cell cultures, ALE and mitraphylline reduced the production of interleukin (IL)-6, and mitraphylline reduced production of tumor necrosis factor-alpha. Treatment with ABE and ALE at 50 and 200â¯mgâ¯kg-1, respectively, reduced respiratory elastance and tissue damping and elastance. ABE and ALE reduced the number of eosinophils in BAL, while ALE at 200â¯mgâ¯kg-1 reduced the levels of IL-4 and IL-5 in the lung homogenate. Peribronchial inflammation was significantly reduced by treatment with ABE and ALE at 50 and 100â¯mgâ¯kg-1 respectively. CONCLUSION: The results clarify for the first time the anti-inflammatory activity of U. tomentosa in a murine model of asthma. Although ABE and ALE exhibited distinct chemical compositions, both extracts inhibited the production of pro-inflammatory cytokines in vitro. In vivo assays revealed that ABE was more effective in treating asthmatic inflammation while ALE was more successful in controlling respiratory mechanics. Both extracts may have promising applications in the phytotherapy of allergic asthma.
Assuntos
Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Hiper-Reatividade Brônquica/tratamento farmacológico , Unha-de-Gato , Extratos Vegetais/uso terapêutico , Ácidos Carbocíclicos/análise , Ácidos Carbocíclicos/farmacologia , Ácidos Carbocíclicos/uso terapêutico , Alérgenos/imunologia , Animais , Antiasmáticos/análise , Antiasmáticos/farmacologia , Anti-Inflamatórios/análise , Anti-Inflamatórios/farmacologia , Asma/imunologia , Hiper-Reatividade Brônquica/imunologia , Líquido da Lavagem Broncoalveolar , Sobrevivência Celular/efeitos dos fármacos , Citocinas/imunologia , Modelos Animais de Doenças , Alcaloides Indólicos/análise , Alcaloides Indólicos/farmacologia , Alcaloides Indólicos/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Camundongos , Ovalbumina/imunologia , Fitoterapia , Casca de Planta , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Folhas de Planta , Células RAW 264.7RESUMO
Several compounds related with plant defense and pharmacological activities have been isolated from sugarcane. Straw phytotoxins and their possible mechanisms of growth inhibition are largely unknown. A bioassay-guided fractionation of the phytotoxic constituents leachated from a sugarcane straw led to the isolation of trans-ferulic (trans-FA), cis-ferulic (cis-FA), vanillic (VA) and syringic (SA) acids. The straw leachates and their identified constituents significantly inhibited root growth of lettuce and four weeds. VA was more phytotoxic to root elongation than FA and SA. The identified phenolic compounds significantly increased leakage of root cell constituents, inhibited dehydrogenase activity and reduced chlorophyll content in lettuce. VA and FA inhibited mitotic index while SA increased cell division. Additive (VA-FA and FA-SA) and synergistic (VA-SA) interactions on root growth were observed at the response level of EC(25). Although the isolated compounds differed in their relative phytotoxic activities, the observed physiological responses suggest that they have a common mode of action. HPLC analysis indicated that sugarcane straw can potentially release 1.43 (ratio 2:1, trans:cis), 1.14 and 0.14mmolkg(-1) (straw dry weight) of FA, VA and SA, respectively. As phenolic acids are often found spatially concentrated in the top soil layers under plant straws, further studies are needed to establish the impact of these compounds in natural settings.