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Beatriz Bermudez - One of the best experts on this subject based on the ideXlab platform.
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Mitraphylline inhibits lipopolysaccharide mediated activation of primary human neutrophils
Phytomedicine, 2016Co-Authors: Sergio Montserratde La Paz, Rocio De La Puerta, Angeles Fernandezarche, A Quilez, Francisco J G Muriana, M D Garciagimenez, Beatriz BermudezAbstract:Abstract Background Mitraphylline (MTP) is the major pentacyclic oxindolic alkaloid presented in Uncaria tomentosa. It has traditionally been used to treat disorders including arthritis, heart disease, cancer, and other inflammatory diseases. However, the specific role of MTP is still not clear, with more comprehensive studies, our understanding of this ancient herbal medicine will continue growing. Hypothesis/Purpose Some studies provided its ability to inhibit proinflamatory cytokines, such as TNF-α, through NF-κB-dependent mechanism. TNF-α primes neutrophils and modulates phagocytic and oxidative burst activities in inflammatory processes. Since, neutrophils represent the most abundant pool of leukocytes in human blood and play a crucial role in inflammation, we aimed to determine the ability of MTP to modulate neutrophil activation and differentially regulate inflammatory-related cytokines. Methods To determine the mechanism of action of MTP, we investigated the effects on LPS-activated human primary neutrophils responses including activation surface markers by FACS and the expression of inflammatory cytokines, measured by real time PCR and ELISA. Results Treatment with MTP reduced the LPS-dependent activation effects. Activated neutrophils (CD16+CD62L−) diminished after MTP administration. Moreover, proinflamatory cytokines (TNF-α, IL-6 or IL-8) expression and secretion were concomitantly reduced, similar to basal control conditions. Conclusion Taken together, our results demonstrate that MTP is able to elicit an anti-inflammatory response that modulates neutrophil activation contributing to the attenuation of inflammatory episodes. Further studies are need to characterize the mechanism by which MTP can affect this pathway that could provide a means to develop MTP as new candidate for inflammatory disease therapies.
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pharmacological effects of Mitraphylline from uncaria tomentosa in primary human monocytes skew toward m2 macrophages
Journal of Ethnopharmacology, 2015Co-Authors: Angeles Fernandezarche, A Quilez, M D Garciagimenez, Montserratde S La Paz, R De La Puerta, F J G Muriana, Beatriz BermudezAbstract:Abstract Ethnopharmacological relevance Uncaria tomentosa (Willdenow ex Roemer & Schultes) DC. (Rubiaceae) is a Peruvian thorny liana, commonly known as “cat׳s claw”, and traditionally used in folk medicine to deal with several inflammatory diseases. Mitraphylline (MTP) is the most abundant pentacyclic oxindolic alkaloid (POA) from U. Tomentosa and has been reported to modify the inflammatory response. Herein, we have sought to identify the mechanisms underlying this modulatory effect of MTP on primary human monocytes and its ability to regulate differentiation processes on human primary monocyte and monocyte-derived macrophages. Material and methods In vitro studies with human primary monocytes and monocyte-derived macrophages were performed. Monocytes and M0 macrophages were exposed to MTP (25 μM) and LPS (100 ng/mL). M0 macrophages were polarized to M1 and M2 phenotypes in the absence or presence of MTP. The activation state of monocytes/macrophages was assessed by flow cytometry, gene expression and protein analysis of different specific markers. Results In human primary monocytes, the incubation of MTP for 24 h reduced the number of classical (CD14 ++ CD16 − ) and intermediate (CD14 ++ CD16 + ) subsets when compared to untreated or LPS-treated cells. MTP also reduced the chemotactic capacity of human primary monocytes. In addition, MTP promoted the polarization of M0 macrophages toward an anti-inflammatory M2 phenotype, the abrogation of the release of pro-inflammatory cytokines such as TNFα, IL-6 or IL-1β, as well as the restoration of markers for M2 macrophages in LPS-treated M1 macrophages. Conclusions Our results suggest that MTP may be a key modulator for regulating the plasticity of monocytes/macrophages and the attenuation of the inflammatory response.
Ana Maria Soares Pereira - One of the best experts on this subject based on the ideXlab platform.
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unnatural spirocyclic oxindole alkaloids biosynthesis in uncaria guianensis
Scientific Reports, 2019Co-Authors: Adriana A Lopes, Bianca Chioca, Bruno Musquiari, Eduardo J Crevelin, Suzelei C Franca, Maria Fatima Das Gracas Fernandes Da Silva, Ana Maria Soares PereiraAbstract:Spiro-oxindole scaffolds have been studied due to their promising therapeutic potential. In the Amazon rainforest there are two important Uncaria species known as “cat’s claw”, which biosynthesize spirocyclic oxindole alkaloids; Uncaria tomentosa (Willd. ex Schult.) DC. and Uncaria guianensis (Aublet) Gmell. We carried out a precursor-directed biosynthesis approach with U. guianensis and successfully obtained oxindole alkaloid analogues with molecular mass corresponding to the addition of a methyl or fluorine group on the oxindole ring using tryptamine analogue precursors. Two of these novel oxindole alkaloid analogues (3b-7-methyl-isoMitraphylline and 3c-6-fluoro-isoMitraphylline) were isolated and characterized by NMR spectroscopy and ESI-QTOF-MS/MS. Having established a substrate feeding protocol for these plantlets, the biosynthetic route for Mitraphylline (1), rhynchophylline (2), isoMitraphylline (3) and isorhynchophylline (4) was also investigated using 13C-precursors (1-13C-D-glucose, 2-13C-tryptophan, 1-13C-DL-glyceraldehyde, and methyl-13C-D-methionine).
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genetic and chemical diversity of uncaria tomentosa willd ex schult dc in the brazilian amazon
PLOS ONE, 2017Co-Authors: Isabela Cristina Gomes Honório, Suzelei C Franca, Mariana Pires De Campos Telles, Ramilla Dos Santos Braga, Valéria Siero Conde Correa, José Alexandre Felizola Diniz Filho, Bianca Waléria Bertoni, Juliana S. Coppede, Ana Maria Soares PereiraAbstract:Uncaria tomentosa (Willd. ex Schult.) DC., a plant native to the Amazon region, is used widely in popular medicine and by the pharmaceutical industry because of its anti-inflammatory activity. However, the survival of this species is endangered by deforestation and indiscriminate collection, and a preservation plan is urgently required. The objectives of this study were to determine the genetic and chemical variability between and within eight populations of U. tomentosa from the Brazilian states of Acre, Para and Amapa, and to investigate possible correlations between genetic and geographical distances, and between geographical distances or altitude and the accumulation of bioactive oxindole alkaloids. Three sequence-related amplified polymorphism (SRAP) markers were employed to fingerprint genomic DNA, and the amounts of Mitraphylline and isoMitraphylline in leaf samples were established by high-performance liquid chromatography. Although significant divergence existed between the tested populations (FST = 0.246), the largest genetic diversity and the highest percentage of polymorphism (95.68%) was found within the population from Mâncio Lima, Acre. Gene flow was considered rather limited (Nm = 1.57), and no correlations between genetic and geographical distances were detected, suggesting that population structure followed an island model. Accumulations of Mitraphylline and isoMitraphylline varied in the range 32.94 to 0.57 and 3.75 to 0.36 mg g-1 dry weight, respectively. The concentration of isoMitraphylline was positively influenced by altitude, such that the population collected at the site with the highest elevation (Tarauaca, Acre) exhibited the greatest alkaloid content. SRAP markers were very efficient in fingerprinting genomic DNA from U. tomentosa populations and clearly showed that genetic variability within populations was greater than between populations. A conservation and management plan should prioritize the creation of germplasm banks to prevent the loss of existing genetic variability, particularly within alkaloid-rich populations such as those of Tarauaca.
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Mean concentrations of Mitraphylline and isoMitraphylline in populations of Uncaria tomentosa collected in the Amazon region of Brazil.
2017Co-Authors: Isabela Cristina Gomes Honório, Mariana Pires De Campos Telles, Ramilla Dos Santos Braga, Suzelei De Castro França, Juliana Da Silva Coppede, Valéria Siero Conde Correa, José Alexandre Felizola Diniz Filho, Bianca Waléria Bertoni, Ana Maria Soares PereiraAbstract:Mean concentrations of Mitraphylline and isoMitraphylline in populations of Uncaria tomentosa collected in the Amazon region of Brazil.
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High performance liquid chromatographic (HPLC) analyses of leaf extracts of three specimens of Uncaria tomentosa populations from the Amazon region of Brazil.
2017Co-Authors: Isabela Cristina Gomes Honório, Mariana Pires De Campos Telles, Ramilla Dos Santos Braga, Suzelei De Castro França, Juliana Da Silva Coppede, Valéria Siero Conde Correa, José Alexandre Felizola Diniz Filho, Bianca Waléria Bertoni, Ana Maria Soares PereiraAbstract:The chromatograms were obtained from specimens collected in: (A) Cruzeiro do Sul, AC, in which peaks labeled a and b correspond to Mitraphylline and isoMitraphylline, respectively; (B) Afuá, PA, in which the peak labeled b corresponds to isoMitraphylline;; (C) Mâncio Lima, AC, in which peaks a and b are absent. Standards (D) Mitraphylline and (E) isoMitraphylline.
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Validation data for Mitraphylline.
2017Co-Authors: Isabela Cristina Gomes Honório, Mariana Pires De Campos Telles, Ramilla Dos Santos Braga, Suzelei De Castro França, Juliana Da Silva Coppede, Valéria Siero Conde Correa, José Alexandre Felizola Diniz Filho, Bianca Waléria Bertoni, Ana Maria Soares PereiraAbstract:Validation data for Mitraphylline.
Ana Maria S. Pereira - One of the best experts on this subject based on the ideXlab platform.
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Genetic structure and chemical diversity in natural populations of Uncaria guianensis (Aubl.) J.F.Gmel. (Rubiaceae)
PLoS ONE, 2018Co-Authors: Isabela Cristina G. Honório, Piero G. Delprete, Frederico Henrique S. Costa, José Alexandre F. Diniz-filho, Juliana Coppede, Mariana Telles, Ramilla Braga, Valéria Correa, Suzelei França, Ana Maria S. PereiraAbstract:Uncaria guianensis is native to the Amazon and is used traditionally as an anti-inflammatory. Natural populations of the species have declined markedly in recent times because of strong anthropic pressure brought about by deforestation and indiscriminate collection. The aim of the present study was to assess the genetic and chemical diversity among eight natural populations of U. guianensis located in the Brazilian states of Acre, Amapá and Amazonas. A set of four primer combinations was employed in sequence-related amplified polymorphism (SRAP) amplifications of leaf DNA, and the fragments were analyzed in an LI-COR model 4300 DNA Analyzer. Genetic variability within the populations (81%) was substantially greater than that detected between them (19%). The highest percentage of polymorphic loci (90.21%) and the largest genetic variability were observed in the population located in Mazagão, Amapá. Genetic differentiation between populations was high (Fst = 0.188) and the studied populations formed three distinct genetic groups (K = 3). The population located in Assis Brasil, Acre, presented the highest average content of the Mitraphylline (0.60 mg/g dry weight,). However, Mitraphylline and isoMitraphylline not detected in most individuals in the studied populations, and it is questionable whether they should be considered as chemical markers of the species. The genetic data confirm the urgent need for conservation programs for U. guianensis, and for further studies aimed at ascertaining the genetic basis and heritability of alkaloid accumulation.
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Mean concentrations of Mitraphylline and isoMitraphylline in populations of Uncaria guianensis collected in the Amazonian region of Brazil.
2018Co-Authors: Isabela Cristina G. Honório, Suzelei C Franca, Valéria Siero Conde Correa, Piero G. Delprete, Juliana S. Coppede, Frederico Henrique S. Costa, Mariana P. C. Telles, Ramilla S. Braga, José Alexandre F. Diniz-filho, Ana Maria S. PereiraAbstract:Mean concentrations of Mitraphylline and isoMitraphylline in populations of Uncaria guianensis collected in the Amazonian region of Brazil.
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Mean concentrations of Mitraphylline (Mit) and isoMitraphylline (Iso) in populations of Uncaria guianensis collected in the Amazonian region of Brazil.
2018Co-Authors: Isabela Cristina G. Honório, Suzelei C Franca, Valéria Siero Conde Correa, Piero G. Delprete, Juliana S. Coppede, Frederico Henrique S. Costa, Mariana P. C. Telles, Ramilla S. Braga, José Alexandre F. Diniz-filho, Ana Maria S. PereiraAbstract:Mean concentrations of Mitraphylline (Mit) and isoMitraphylline (Iso) in populations of Uncaria guianensis collected in the Amazonian region of Brazil.
Montserratde S La Paz - One of the best experts on this subject based on the ideXlab platform.
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pharmacological effects of Mitraphylline from uncaria tomentosa in primary human monocytes skew toward m2 macrophages
Journal of Ethnopharmacology, 2015Co-Authors: Angeles Fernandezarche, A Quilez, M D Garciagimenez, Montserratde S La Paz, R De La Puerta, F J G Muriana, Beatriz BermudezAbstract:Abstract Ethnopharmacological relevance Uncaria tomentosa (Willdenow ex Roemer & Schultes) DC. (Rubiaceae) is a Peruvian thorny liana, commonly known as “cat׳s claw”, and traditionally used in folk medicine to deal with several inflammatory diseases. Mitraphylline (MTP) is the most abundant pentacyclic oxindolic alkaloid (POA) from U. Tomentosa and has been reported to modify the inflammatory response. Herein, we have sought to identify the mechanisms underlying this modulatory effect of MTP on primary human monocytes and its ability to regulate differentiation processes on human primary monocyte and monocyte-derived macrophages. Material and methods In vitro studies with human primary monocytes and monocyte-derived macrophages were performed. Monocytes and M0 macrophages were exposed to MTP (25 μM) and LPS (100 ng/mL). M0 macrophages were polarized to M1 and M2 phenotypes in the absence or presence of MTP. The activation state of monocytes/macrophages was assessed by flow cytometry, gene expression and protein analysis of different specific markers. Results In human primary monocytes, the incubation of MTP for 24 h reduced the number of classical (CD14 ++ CD16 − ) and intermediate (CD14 ++ CD16 + ) subsets when compared to untreated or LPS-treated cells. MTP also reduced the chemotactic capacity of human primary monocytes. In addition, MTP promoted the polarization of M0 macrophages toward an anti-inflammatory M2 phenotype, the abrogation of the release of pro-inflammatory cytokines such as TNFα, IL-6 or IL-1β, as well as the restoration of markers for M2 macrophages in LPS-treated M1 macrophages. Conclusions Our results suggest that MTP may be a key modulator for regulating the plasticity of monocytes/macrophages and the attenuation of the inflammatory response.
Piero G. Delprete - One of the best experts on this subject based on the ideXlab platform.
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Genetic structure and chemical diversity in natural populations of Uncaria guianensis (Aubl.) J.F.Gmel. (Rubiaceae)
PLoS ONE, 2018Co-Authors: Isabela Cristina G. Honório, Piero G. Delprete, Frederico Henrique S. Costa, José Alexandre F. Diniz-filho, Juliana Coppede, Mariana Telles, Ramilla Braga, Valéria Correa, Suzelei França, Ana Maria S. PereiraAbstract:Uncaria guianensis is native to the Amazon and is used traditionally as an anti-inflammatory. Natural populations of the species have declined markedly in recent times because of strong anthropic pressure brought about by deforestation and indiscriminate collection. The aim of the present study was to assess the genetic and chemical diversity among eight natural populations of U. guianensis located in the Brazilian states of Acre, Amapá and Amazonas. A set of four primer combinations was employed in sequence-related amplified polymorphism (SRAP) amplifications of leaf DNA, and the fragments were analyzed in an LI-COR model 4300 DNA Analyzer. Genetic variability within the populations (81%) was substantially greater than that detected between them (19%). The highest percentage of polymorphic loci (90.21%) and the largest genetic variability were observed in the population located in Mazagão, Amapá. Genetic differentiation between populations was high (Fst = 0.188) and the studied populations formed three distinct genetic groups (K = 3). The population located in Assis Brasil, Acre, presented the highest average content of the Mitraphylline (0.60 mg/g dry weight,). However, Mitraphylline and isoMitraphylline not detected in most individuals in the studied populations, and it is questionable whether they should be considered as chemical markers of the species. The genetic data confirm the urgent need for conservation programs for U. guianensis, and for further studies aimed at ascertaining the genetic basis and heritability of alkaloid accumulation.
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Aqueous extracts from Uncaria tomentosa (Willd. ex Schult.) DC. reduce bronchial hyperresponsiveness and inflammation in a murine model of asthma
Journal of Ethnopharmacology, 2018Co-Authors: Bruna Cestari Azevedo, Lucas Junqueira Freitas Morel, Fábio Carmona, Thiago Mattar Cunha, Silvia Helena Taleb Contini, Piero G. Delprete, Fernando Silva Ramalho, Eduardo Crevelin, Bianca Waléria Bertoni, Suzelei Castro FrançaAbstract: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.
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Mean concentrations of Mitraphylline and isoMitraphylline in populations of Uncaria guianensis collected in the Amazonian region of Brazil.
2018Co-Authors: Isabela Cristina G. Honório, Suzelei C Franca, Valéria Siero Conde Correa, Piero G. Delprete, Juliana S. Coppede, Frederico Henrique S. Costa, Mariana P. C. Telles, Ramilla S. Braga, José Alexandre F. Diniz-filho, Ana Maria S. PereiraAbstract:Mean concentrations of Mitraphylline and isoMitraphylline in populations of Uncaria guianensis collected in the Amazonian region of Brazil.
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Mean concentrations of Mitraphylline (Mit) and isoMitraphylline (Iso) in populations of Uncaria guianensis collected in the Amazonian region of Brazil.
2018Co-Authors: Isabela Cristina G. Honório, Suzelei C Franca, Valéria Siero Conde Correa, Piero G. Delprete, Juliana S. Coppede, Frederico Henrique S. Costa, Mariana P. C. Telles, Ramilla S. Braga, José Alexandre F. Diniz-filho, Ana Maria S. PereiraAbstract:Mean concentrations of Mitraphylline (Mit) and isoMitraphylline (Iso) in populations of Uncaria guianensis collected in the Amazonian region of Brazil.