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来自黄花远志(A.W. Bennett)的7-异戊烯氧基-6-甲氧基香豆素调节p38丝裂原活化蛋白激酶和核因子κB信号通路,抑制角叉菜胶诱导的小鼠胸膜炎模型中的炎症反应。

7-prenyloxi-6-methoxycoumarin from Polygala sabulosa A.W. Bennett Regulates p38 MAPK and NF-kB Pathways Inhibiting the Inflammation Induced by Carrageenan in the Mouse Model of Pleurisy.

作者信息

Dos Santos Nascimento Marcus Vinicius Pereira, Arruda-Silva Fábio, Luz Ana Beatriz G, Venzke Dalila, Queiroz Gustavo S, Mendes Beatriz G, Fernandes-Ribeiro Eduardo R, Fröde Tânia S, Pizzolatti Moacir G, Dalmarco Eduardo M

机构信息

Department of Clinical Analyses, Centre of Health Sciences, Federal University of Santa Catarina, Campus Universitário - Trindade, 88040-970, Florianopolis, SC, Brazil.

出版信息

Inflamm Allergy Drug Targets. 2015;14(1):37-46. doi: 10.2174/1871528114666151005125120.

Abstract

CONTEXT

Polygala sabulosa, popularly known as "timutu-pinheirinho," has been used in Brazilian folk medicine for the treatment of bowel and kidney disorders and as an expectorant.

OBJECTIVE

Evaluate the anti-inflammatory effects of the crude extract (CE), acetonic fraction (Ac), and the main compound, 7-prenyloxi-6-methoxycoumarin (PC) on a mouse model of carrageenan-induced pleurisy.

MATERIALS AND METHODS

A mouse model of carrageenan-induced pleurisy was used to investigate the effects of P. sabulosa CE, Ac and PC on leukocyte migration, exudate formation, activities of myeloperoxidase (MPO), and adenosine-deaminase (ADA), levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and nitric oxide (NO). In addition, the effect of the plant material on lung histology was also evaluated. The effects of PC on the TNF-α, IL-1β and NO synthase 2 (NOS2) mRNA expression, were also investigated. Finally, the effect of PC on the nuclear factor-kappa B (NF-κB) and p38 mitogen-activated protein kinase (p38 MAPK) was also evaluated.

RESULTS

CE, Ac and PC reduced inflammation in the pleural cavity and lungs. This effect was evidenced by reduction on all inflammatory parameters evaluated; the exception being the inability of the CE to inhibit exudate formation. In isolation, PC showed reduction on mRNA levels of TNF-α, IL-1β and NOS2, and on activation of the NF-κB and p38 MAPK pathways.

CONCLUSION

The presented results show that P. sabulosa has significant anti-inflammatory activity, as does its main compound, PC. Moreover, the results suggest that PC exerts its effects mainly by inhibited the NF-κB and p38 MAPK pathways.

摘要

背景

远志(Polygala sabulosa),俗称“timutu-pinheirinho”,在巴西民间医学中用于治疗肠道和肾脏疾病以及作为祛痰剂。

目的

评估粗提物(CE)、丙酮提取物(Ac)以及主要化合物7-异戊烯氧基-6-甲氧基香豆素(PC)对角叉菜胶诱导的小鼠胸膜炎模型的抗炎作用。

材料与方法

采用角叉菜胶诱导的小鼠胸膜炎模型,研究远志CE、Ac和PC对白细胞迁移、渗出物形成、髓过氧化物酶(MPO)和腺苷脱氨酶(ADA)活性、肿瘤坏死因子-α(TNF-α)、白细胞介素1β(IL-1β)和一氧化氮(NO)水平的影响。此外,还评估了该植物材料对肺组织学的影响。研究了PC对TNF-α、IL-1β和一氧化氮合酶2(NOS2)mRNA表达的影响。最后,还评估了PC对核因子-κB(NF-κB)和p38丝裂原活化蛋白激酶(p38 MAPK)的影响。

结果

CE、Ac和PC减轻了胸腔和肺部的炎症。所有评估的炎症参数均降低证明了这种作用;唯一的例外是CE无法抑制渗出物形成。单独使用时,PC降低了TNF-α、IL-1β和NOS2的mRNA水平,以及NF-κB和p38 MAPK途径的激活。

结论

所呈现的结果表明,远志具有显著的抗炎活性,其主要化合物PC也是如此。此外,结果表明PC主要通过抑制NF-κB和p38 MAPK途径发挥作用。

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