Natural Products as a Source for New Anti-Inflammatory and Analgesic Compounds through the Inhibition of Purinergic P2X Receptors

Made available in DSpace on 2015-09-21T17:25:30Z (GMT). No. of bitstreams: 2 license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) romulo_bezerra_etal_IOC_2013.pdf: 134441 bytes, checksum: d4f6fd4f106a4ff0b18c0b69e9fa9db5 (MD5) Previous issue date: 2013Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Comunicação Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Comunicação Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Comunicação Celular. Rio de Janeiro, RJ, Brasil.Natural products have reemerged in traditional medicine as a potential source of new molecules or phytomedicines to help with health disorders. It has been established that members of the P2X subfamily, ATP-gated ion channels, are crucial to the inflammatory process and pain signalization. As such, several preclinical studies have demonstrated that P2X2R, P2X3R, P2X4R and P2X7R are promising pharmacological targets to control inflammatory and pain disorders. Several studies have indicated that natural products could be a good source of the new specific molecules needed for the treatment of diseases linked to inflammation and pain disorders through the regulation of these receptors. Herein, we discuss and give an overview of the applicability of natural products as a source to obtain P2X receptors (P2XR) selective antagonists for use in clinical treatment, which require further investigation

Curine Inhibits Macrophage Activation and Neutrophil Recruitment in a Mouse Model of Lipopolysaccharide-Induced Inflammation

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2020-01-21T12:11:49Z No. of bitstreams: 1 Ribeiro-Filho j Curine Inhibits Tosins.pdf: 4153596 bytes, checksum: cc6b46647db9fe4e1ee57c25f4dcf6a8 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2020-01-21T12:21:53Z (GMT) No. of bitstreams: 1 Ribeiro-Filho j Curine Inhibits Tosins.pdf: 4153596 bytes, checksum: cc6b46647db9fe4e1ee57c25f4dcf6a8 (MD5)Made available in DSpace on 2020-01-21T12:21:53Z (GMT). No. of bitstreams: 1 Ribeiro-Filho j Curine Inhibits Tosins.pdf: 4153596 bytes, checksum: cc6b46647db9fe4e1ee57c25f4dcf6a8 (MD5) Previous issue date: 2019-01-03PRONEX/MCT, CNPq, FAPERJ and INCT-Câncer.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemias. Departamento de Análises Clínicas e Toxicologicas. Salvador, BA, Brasil.Universidade Federal da Paraíba. Laboratório de Imunofarmacologia. Departamento de Fisiologia e Patologia. João Pessoa, PB, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal da Paraíba. Laboratório de Fitoquímica. Departamento de Ciências Farmacêuticas. João Pessoa, PB, Brasil.Universidade Federal da Paraíba. Laboratório de Imunofarmacologia. Departamento de Fisiologia e Patologia. João Pessoa, PB, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Curine is a bisbenzylisoquinoline alkaloid (BBA) with anti-allergic, analgesic, and anti-inflammatory properties. Previous studies have demonstrated that this alkaloid is orally active at non-toxic doses. However, the mechanisms underlying its anti-inflammatory effects remain to be elucidated. This work aimed to investigate the effects of curine on macrophage activation and neutrophil recruitment. Using a murine model of lipopolysaccharide (LPS)-induced pleurisy, we demonstrated that curine significantly inhibited the recruitment of neutrophils in association with the inhibition of cytokines tumor necrosis factor (TNF-α), interleukin (IL)-1β, IL-6, monocyte chemotactic protein (CCL2/MCP-1) as well as leukotriene B4 in the pleural lavage of mice. Curine treatment reduced cytokine levels and the expression of iNOS in in vitro cultures of macrophages stimulated with LPS. Treatment with a calcium channel blocker resulted in comparable inhibition of TNF-α and IL-1β production, as well as iNOS expression by macrophages, suggesting that the anti-inflammatory effects of curine may be related to the inhibition of calcium-dependent mechanisms involved in macrophage activation. In conclusion, curine presented anti-inflammatory effects that are associated with inhibition of macrophage activation and neutrophil recruitment by inhibiting the production of inflammatory cytokines, LTB4 and nitric oxide (NO), and possibly by negatively modulating Ca2+ influx

Curine, an Alkaloid Isolated from Chondrodendron platyphyllum Inhibits Prostaglandin E2 in Experimental Models of Inflammation and Pain

Made available in DSpace on 2015-05-27T13:39:52Z (GMT). No. of bitstreams: 2 license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) andrea_calheirosetal_IOC_2014.pdf: 179135 bytes, checksum: 2fd469793ee7706daa823c19306c4119 (MD5) Previous issue date: 2014Universidade Federal da Paraíba. Departamento de Fisiologia e Patologia. Laboratório de Imunofarmacologia. João Pessoa, PB, Brasil .Universidade Federal da Paraíba. Departamento de Fisiologia e Patologia. Laboratório de Imunofarmacologia. João Pessoa, PB, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal da Paraíba. Departamento de Fisiologia e Patologia. Laboratório de Imunofarmacologia. João Pessoa, PB, Brasil .Universidade Federal da Paraíba. Departamento de Fisiologia e Patologia. Laboratório de Psicofarmacologia. João Pessoa, PB, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal da Paraíba. Departamento de Fisiologia e Patologia. Laboratório de Psicofarmacologia. João Pessoa, PB, Brasil.Universidade Federal da Paraíba. Departamento de Ciências Farmacêuticas. Laboratório de Fitoquímica. João Pessoa, PB, Brasil.Curine is a bisbenzylisoquinoline alkaloid that is isolated from Chondrodendron platyphyllum, a plant that is used to treat malaria, inflammation, and pain. Recent reports have demonstrated the antiallergic effects of curine at nontoxic doses. However, its anti-inflammatory and analgesic properties remain to be elucidated. This study investigated the anti-inflammatory and analgesic effects of curine in mice. We analyzed the effects of an oral treatment with curine in the formation of paw edema, vascular permeability, abdominal contortion, licking behavior, and hyperalgesia using different inflammatory stimuli. Curine significantly inhibited the formation of paw edema by decreasing vascular permeability, inhibited the acetic acid-induced writhing response, inhibited the licking behavior during inflammation but not during the neurogenic phase of the formalin test, and inhibited carrageenan-induced hyperalgesia. Finally, curine inhibited prostaglandin E2 production in vitro without affecting cyclooxygenase-2 expression. The effects of curine treatment were similar to the effects of indomethacin, but were different from the effects of morphine treatment, suggesting that the analgesic effects of curine do not result from the direct inhibition of neuronal activation but instead depend on anti-inflammatory mechanisms that, at least in part, result from the inhibition of prostaglandin E2 production. In conclusion, curine presents anti-inflammatory and analgesic effects at nontoxic doses and has the potential for use in anti-inflammatory drug development

Pannexin-1 Blockage Assay in U937 Cells.

<p>U937 cells were plated in opaque 96-well plates following the subsequent treatments: a) Cells plus PI [50 nM]; b) cells plus Triton X-100 [0.1%] plus PI [50 nM]; c) cells plus ATP [5 mM] plus PI [50 nM]; d) cells plus BBG [100 nM] plus PI [50 nM]; e) cells plus Carbenoxolone [100 μM] plus PI [50 nM]; f) cells plus Mefloquine [1 μM] plus PI [50 nM]; g) cells plus AZ11645373 [10 μM] plus PI [50 nM]; h) cells plus BBG [100 nM] plus ATP [5 mM] plus PI [50 nM]; i) cells plus Carbenoxolone [100 μM] plus PI [50 nM] plus ATP [5 mM]; j) Cell plus Mefloquine [1 μM] plus ATP [5 mM] plus PI [50 nM]; l) cells plus AZ11645373 [10 μM] plus PI [50 nM] plus ATP [5 mM]. Date represents mean ± S.D of three independent experiments in triplicate. The result was analyzed using the Kruskal-Wallis, followed by Dunns post-hoc analysis; * p<0.05.</p

Time course of pulmonary burden in mice exposed to residual oil fly ash

Made available in DSpace on 2015-05-27T13:39:48Z (GMT). No. of bitstreams: 2 license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) andrea_calheiros2etal_IOC_2014.pdf: 1247651 bytes, checksum: 64f6743d18deb5398037d4d1c504f8cc (MD5) Previous issue date: 2014Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Fisiologia Respiratória. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Fisiologia Respiratória. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Fisiologia Respiratória. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Fisiologia Respiratória. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Departamento de Fisiologia e Farmodinâmica. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Radioisótopos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Departamento de Fisiologia e Farmodinâmica. Rio de Janeiro, RJ, Brasil.Universidade de São Paulo. Escola de Medicina. Departamento de Patologia. Laboratório Experimental de Poluição Atmosférica. São Paulo, SP, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Metabolismo Macromolecular Firmino Torres de Castro. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Investigação Pulmonar. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Fisiologia Respiratória. Rio de Janeiro, RJ, Brasil.Residual oil fly ash (ROFA) is a common pollutant in areas where oil is burned. This particulate matter (PM) with a broad distribution of particle diameters can be inhaled by human beings and putatively damage their respiratory system. Although some studies deal with cultured cells, animals, and even epidemiological issues, so far a comprehensive analysis of respiratory outcomes as a function of the time elapsed after exposure to a low dose of ROFA is wanted. Thus, we aimed to investigate the time course of mechanical, histological, and inflammatory lung changes, as well as neutrophils in the blood, in mice exposed to ROFA until 5 days after exposure. BALB/c mice (25 ± 5 g) were randomly divided into 7 groups and intranasally instilled with either 10 μL of sterile saline solution (0.9% NaCl, CTRL) or ROFA (0.2 μg in 10 μL of saline solution). Pulmonary mechanics, histology (normal and collapsed alveoli, mononuclear and polymorphonuclear cells, and ultrastructure), neutrophils (in blood and bronchoalveolar lavage fluid) were determined at 6 h in CTRL and at 6, 24, 48, 72, 96, and 120 h after ROFA exposure. ROFA contained metal elements, especially iron, polycyclic aromatic hydrocarbons (PAHs), and organochlorines. Lung resistive pressure augmented early (6 h) in the course of lung injury and other mechanical, histological and inflammatory parameters increased at 24 h, returning to control values at 120 h. Blood neutrophilia was present only at 24 and 48 h after exposure. Swelling of endothelial cells with adherent neutrophils was detected after ROFA instillation. No neutrophils were present in the lavage fluid. In conclusion, the exposure to ROFA, even in low doses, induced early changes in pulmonary mechanics, lung histology and accumulation of neutrophils in blood of mice that lasted for 4 days and disappeared spontaneously

OATP dose-response curve.

<p>J774.G8 cells were plated in opaque 96-well plates and treated with various concentrations of OATP from 0.048 to 400 μM. The data represent the means ± S.D. of three independent experiments in triplicate. The results were analyzed using the Kruskal-Wallis, followed by Dunns post-hoc analysis; * p<0.05.</p

ATP dose-response curve.

<p>J774.G8 cells were plated in opaque 96-well plates and treated with various concentrations of ATP from 0.321 to 25 mM in combination with PI [50 nM]. The data represent the means ± S.D. of three independent experiments in triplicate. The results were analyzed using the Kruskal-Wallis, followed by Dunns post-hoc analysis; * p<0.05.</p

BBG dose-response curve.

<p>J774.G8 cells were plated in opaque 96-well plates and treated with various concentrations of BBG from 0.048 to 100 μM in combination with PI [50 nM] and ATP [5 mM]. The data represent the means ± S.D. of three independent experiments in triplicate. The results were analyzed using the Kruskal-Wallis, followed by Dunns post-hoc analysis; * p<0.05.</p

IC₅₀ or EC₅₀ values for P2X7R agonists or antagonists using different methods.

<p>*IC₅₀ for natively expressed mP2X7R in J774.G8 cells.</p><p>**N.D. = Not determined</p><p>IC₅₀ or EC₅₀ values for P2X7R agonists or antagonists using different methods.</p