Bruna Cestari Azevedo1, Lucas Junqueira Freitas Morel1, Fábio Carmona2, Thiago Mattar Cunha2, Silvia Helena Taleb Contini1, Piero Giuseppe Delprete3, Fernando Silva Ramalho2, Eduardo Crevelin4, Bianca Waléria Bertoni1, Suzelei Castro França1, Marcos Carvalho Borges2, Ana Maria Soares Pereira5. 1. Departamento de Biotecnologia em Plantas Medicinais, Universidade de Ribeirão Preto, Av. Costábile Romano 2201, 14096-900 Ribeirão Preto, SP, Brazil. 2. Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, Monte Alegre, 14049-900 Ribeirão Preto, SP, Brazil. 3. Herbier de Guyane, Institut de Recherche pour le Développement, 275 Route de Montabo, BP 90165, 97323 Cayenne Cedex, French Guiana. 4. Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, Monte Alegre, 14049-900 Ribeirão Preto, SP, Brazil. 5. Departamento de Biotecnologia em Plantas Medicinais, Universidade de Ribeirão Preto, Av. Costábile Romano 2201, 14096-900 Ribeirão Preto, SP, Brazil. Electronic address: apereira@unaerp.br.
Abstract
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 200 mg kg-1, respectively, reduced respiratory elastance and tissue damping and elastance. ABE and ALE reduced the number of eosinophils in BAL, while ALE at 200 mg 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 100 mg 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.
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 200 mg kg-1, respectively, reduced respiratory elastance and tissue damping and elastance. ABE and ALE reduced the number of eosinophils in BAL, while ALE at 200 mg 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 100 mg 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.
Authors: Bruna C Azevedo; Mariana Roxo; Marcos C Borges; Herbenya Peixoto; Eduardo J Crevelin; Bianca W Bertoni; Silvia H T Contini; Adriana A Lopes; Suzelei C França; Ana M S Pereira; Michael Wink Journal: Molecules Date: 2019-09-10 Impact factor: 4.411
Authors: Mackeler Ramos Polassi; Thales de Sá Oliveira; Ana Calheiros de Carvalho; Lívia Soman de Medeiros Medeiros; Thiago André Moura Veiga; Carlos Frederico de Oliveira Graeff; Alejandra Hortencia Miranda González; Maria Cristina Marcucci; Simone Dos Santos Grecco; Paulo Henrique Perlatti D'Alpino Journal: ScientificWorldJournal Date: 2021-06-15