评估 1,4-二氢吡啶衍生物的抗炎作用。

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY
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
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引用次数: 0

摘要

导言炎症是一种生理现象,可保护机体免受导致组织失去平衡的各种因素的影响。二氢吡啶(DHP)衍生物是一种杂环化合物,具有不同的生物活性,包括抗炎活性:目的:利用体外抗炎模型,在脂多糖(LPS)诱导的 RAW264.7 细胞中评估 1,4-二氢吡啶(1,4-DHP)衍生物的抗炎活性;利用体内急性肺损伤(ALI)模型,在小鼠体内评估 1,4-二氢吡啶(1,4-DHP)衍生物的抗炎活性:在 RAW264.7 细胞中测试了 15 种 1,4-DHP 衍生化合物的细胞毒性作用和细胞活力。之后,仅对细胞活力最高的 6 种化合物进行了促炎细胞因子白细胞介素 6 (IL-6) 的产生或抑制测试。对最佳化合物(化合物 4)的体外和体内抗炎效果进行了测试,结果表明其抑制了一氧化氮(NO)、促炎细胞因子、提高了吞噬活性,并增加了体外 IL-10 的含量。在体内试验中,化合物 4 还能降低一氧化氮、髓过氧化物酶(MPO)活性、白细胞迁移和渗出的水平,降低肿瘤坏死因子-α(TNF-α)和 IL-6 的水平,防止肺部结构的损失:该化合物具有重要的抗炎活性,能显著减少促炎介质的产生,提高巨噬细胞的吞噬活性和抗炎介质(IL-10)的分泌。这些发现使我们推测,这种化合物能将巨噬细胞的反应重新极化为抗炎特征(M2)。此外,它还能在体内实验中保持其抗炎活性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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来源期刊
CiteScore
5.30
自引率
6.90%
发文量
111
审稿时长
6-12 weeks
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.
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