Bruno Matheus Facchin, Tainá Larissa Lubschinski, Yeo Jim Kinoshita Moon, Paula Giarola Fragoso de Oliveira, Bianca Klafke Beck, Ziliani da Silva Buss, Luiz Antonio Escorteganha Pollo, Maique Weber Biavatti, Louis Pergaud Sandjo, Eduardo Monguilhott Dalmarco
{"title":"评估 1,4-二氢吡啶衍生物的抗炎作用。","authors":"Bruno Matheus Facchin, Tainá Larissa Lubschinski, Yeo Jim Kinoshita Moon, Paula Giarola Fragoso de Oliveira, Bianca Klafke Beck, Ziliani da Silva Buss, Luiz Antonio Escorteganha Pollo, Maique Weber Biavatti, Louis Pergaud Sandjo, Eduardo Monguilhott Dalmarco","doi":"10.1111/fcp.12945","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Introduction</h3>\n \n <p>Inflammation is a physiological event that protects the organism against different factors that lead to loss of tissue homeostasis. Dihydropyridine (DHP) derivatives are heterocyclic compounds known for their different biological activities, including anti-inflammatory activities.</p>\n </section>\n \n <section>\n \n <h3> Objective</h3>\n \n <p>To evaluate the anti-inflammatory activity of 1,4-dihydropyridine (1,4-DHP) derivatives using anti-inflammatory models in vitro, in RAW264.7 cells induced by lipopolysaccharide (LPS) and in vivo using the acute lung injury (ALI) model in mice.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Fifteen compounds derived from 1,4-DHP were tested in RAW264.7 cells for their cytotoxic effect and cell viability. Thereafter, only the six compounds that showed the highest cell viability were tested for the production or inhibition of the pro-inflammatory cytokine interleukin 6 (IL-6). The best compound (compound 4) was tested for its anti-inflammatory effects in vitro and in vivo, showing inhibition of nitric oxide (NO), pro-inflammatory cytokines, increased phagocytic activity, and an increase in IL-10 in vitro. In in vivo tests, compound 4 also reduces the levels of NO, myeloperoxidase (MPO) activity, leukocyte migration, and exudation, as well as reducing the levels of tumor necrosis factor-alpha (TNF-α) and IL-6 and preventing the loss in the lung architecture.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>This compound showed important anti-inflammatory activity, with a significant ability to reduce the production of pro-inflammatory mediators and increase the phagocytic activity of macrophages and anti-inflammatory mediator secretion (IL-10). These findings led us to hypothesize that this compound can repolarize the macrophage response to an anti-inflammatory profile (M2). Moreover, it was also able to maintain its anti-inflammatory activity in vivo experiments.</p>\n </section>\n </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2023-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Evaluation of the anti-inflammatory effect of 1,4-dihydropyridine derivatives\",\"authors\":\"Bruno Matheus Facchin, Tainá Larissa Lubschinski, Yeo Jim Kinoshita Moon, Paula Giarola Fragoso de Oliveira, Bianca Klafke Beck, Ziliani da Silva Buss, Luiz Antonio Escorteganha Pollo, Maique Weber Biavatti, Louis Pergaud Sandjo, Eduardo Monguilhott Dalmarco\",\"doi\":\"10.1111/fcp.12945\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Introduction</h3>\\n \\n <p>Inflammation is a physiological event that protects the organism against different factors that lead to loss of tissue homeostasis. 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The best compound (compound 4) was tested for its anti-inflammatory effects in vitro and in vivo, showing inhibition of nitric oxide (NO), pro-inflammatory cytokines, increased phagocytic activity, and an increase in IL-10 in vitro. In in vivo tests, compound 4 also reduces the levels of NO, myeloperoxidase (MPO) activity, leukocyte migration, and exudation, as well as reducing the levels of tumor necrosis factor-alpha (TNF-α) and IL-6 and preventing the loss in the lung architecture.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>This compound showed important anti-inflammatory activity, with a significant ability to reduce the production of pro-inflammatory mediators and increase the phagocytic activity of macrophages and anti-inflammatory mediator secretion (IL-10). These findings led us to hypothesize that this compound can repolarize the macrophage response to an anti-inflammatory profile (M2). 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Evaluation of the anti-inflammatory effect of 1,4-dihydropyridine derivatives
Introduction
Inflammation is a physiological event that protects the organism against different factors that lead to loss of tissue homeostasis. Dihydropyridine (DHP) derivatives are heterocyclic compounds known for their different biological activities, including anti-inflammatory activities.
Objective
To evaluate the anti-inflammatory activity of 1,4-dihydropyridine (1,4-DHP) derivatives using anti-inflammatory models in vitro, in RAW264.7 cells induced by lipopolysaccharide (LPS) and in vivo using the acute lung injury (ALI) model in mice.
Results
Fifteen compounds derived from 1,4-DHP were tested in RAW264.7 cells for their cytotoxic effect and cell viability. Thereafter, only the six compounds that showed the highest cell viability were tested for the production or inhibition of the pro-inflammatory cytokine interleukin 6 (IL-6). The best compound (compound 4) was tested for its anti-inflammatory effects in vitro and in vivo, showing inhibition of nitric oxide (NO), pro-inflammatory cytokines, increased phagocytic activity, and an increase in IL-10 in vitro. In in vivo tests, compound 4 also reduces the levels of NO, myeloperoxidase (MPO) activity, leukocyte migration, and exudation, as well as reducing the levels of tumor necrosis factor-alpha (TNF-α) and IL-6 and preventing the loss in the lung architecture.
Conclusion
This compound showed important anti-inflammatory activity, with a significant ability to reduce the production of pro-inflammatory mediators and increase the phagocytic activity of macrophages and anti-inflammatory mediator secretion (IL-10). These findings led us to hypothesize that this compound can repolarize the macrophage response to an anti-inflammatory profile (M2). Moreover, it was also able to maintain its anti-inflammatory activity in vivo experiments.
期刊介绍:
Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including:
Antimicrobial, Antiviral Agents
Autonomic Pharmacology
Cardiovascular Pharmacology
Cellular Pharmacology
Clinical Trials
Endocrinopharmacology
Gene Therapy
Inflammation, Immunopharmacology
Lipids, Atherosclerosis
Liver and G-I Tract Pharmacology
Metabolism, Pharmacokinetics
Neuropharmacology
Neuropsychopharmacology
Oncopharmacology
Pediatric Pharmacology Development
Pharmacoeconomics
Pharmacoepidemiology
Pharmacogenetics, Pharmacogenomics
Pharmacovigilance
Pulmonary Pharmacology
Receptors, Signal Transduction
Renal Pharmacology
Thrombosis and Hemostasis
Toxicopharmacology
Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.