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季节性对戈亚泽内酯含量以及对巴西土木香乙醇提取物的抗炎和抗高尿酸血症作用的影响。

The influence of seasonality on the content of goyazensolide and on anti-inflammatory and anti-hyperuricemic effects of the ethanolic extract of Lychnophora passerina (Brazilian arnica).

作者信息

de Albuquerque Ugoline Bruno César, de Souza Jacqueline, Ferrari Fernanda Cristina, Ferraz-Filha Zilma Schimith, Coelho Grazielle Brandão, Saúde-Guimarães Dênia Antunes

机构信息

Laboratório de Plantas Medicinais (LAPLAMED), CiPharma, Escola de Farmácia, Campus da Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais 35400-000, Brazil.

Laboratório de Controle de Qualidade, CiPharma, Escola de Farmácia, Campus da Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais 35400-000, Brazil.

出版信息

J Ethnopharmacol. 2017 Feb 23;198:444-450. doi: 10.1016/j.jep.2017.01.017. Epub 2017 Jan 12.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Lychnophora passerina (Mart ex DC) Gardn (Asteraceae), popularly known as Brazilian arnica, is used in Brazilian folk medicine to treat pain, rheumatism, bruises, inflammatory diseases and insect bites.

AIM OF THE STUDY

Investigate the influence of the seasons on the anti-inflammatory and anti-hyperuricemic activities of ethanolic extract of L. passerina and the ratio of the goyazensolide content, main chemical constituent of the ethanolic extract, with these activities.

MATERIALS AND METHODS

Ethanolic extracts of aerial parts of L. passerina were obtained from seasons: summer (ES), autumn (EA), winter (EW) and spring (EP). The sesquiterpene lactone goyazensolide, major metabolite, was quantified in ES, EA, EW and EP by a developed and validated HPLC-DAD method. The in vivo anti-hyperuricemic and anti-inflammatory effects of the ethanolic extracts from L. passerina and goyazensolide were assayed on experimental model of oxonate-induced hyperuricemia in mice, liver xanthine oxidase (XOD) inhibition and on carrageenan-induced paw edema in mice.

RESULTS

HPLC method using aqueous solution of acetic acid 0.01% (v/v) and acetonitrile with acetic acid 0.01% (v/v) as a mobile phase in a gradient system, with coumarin as an internal standard and DAD detection at 270nm was developed. The validation parameters showed linearity in a range within 10.0-150.0µg/ml, with intraday and interday precisions a range of 0.61-3.82. The accuracy values of intraday and interday analysis within 87.58-100.95%. EA showed the highest goyazensolide content. From the third to the sixth hour after injection of carrageenan, treatments with all extracts at the dose of 125mg/kg were able to reduce edema. Goyazensolide (10mg/kg) showed significant reduction of paw swelling from the second hour assay. This sesquiterpene lactone was more active than extracts and presented similar effect to indomethacin. Treatments with ES, EA and EP (125mg/kg) and goyazensolide (10mg/kg) reduced serum urate levels compared to hyperuricemic control group and were able to inhibit liver XOD activity. One of the mechanisms by which ES, EA, EP and goyazensolide exercise their anti-hyperuricemic effect is by the inhibition of liver XOD activity. Goyazensolide was identified as the main compound present in ES, EA, EW and EP and it is shown to be one of the chemical constituents responsible for the anti-inflammatory and anti-hyperuricemic effects of the ethanolic extracts.

CONCLUSION

The anti-inflammatory and anti-hyperuricemic activities of the ethanolic extracts from L. passerina were not proportionally influenced by the variation of goyazensolide content throughout the seasons. The involvement of goyazensolide on in vivo anti-inflammatory and anti-hyperuricemic activities of L.passerina extracts was confirmed, as well as the possibility of participation of other constituents on these effects. This study demonstrated that the aerial parts of L. passerina may be collected in any season for use as anti-inflammatory agent. For use in hyperuricemia, the best seasons for the collection are summer, autumn and spring. The ethanolic extract of L. passerina and goyazensolide can be considered promising agents in the therapeutic of inflammation, hyperuricemia and gout.

摘要

民族药理学相关性

灯笼草(Lychnophora passerina (Mart ex DC) Gardn,菊科),俗称巴西山金车,在巴西民间医学中用于治疗疼痛、风湿、瘀伤、炎症性疾病和昆虫叮咬。

研究目的

研究季节对灯笼草乙醇提取物抗炎和抗高尿酸血症活性的影响,以及乙醇提取物的主要化学成分戈亚泽内酯含量与这些活性之间的关系。

材料与方法

从夏季(ES)、秋季(EA)、冬季(EW)和春季(EP)采集灯笼草地上部分的乙醇提取物。采用开发并验证的高效液相色谱-二极管阵列检测法(HPLC-DAD)对ES、EA、EW和EP中的倍半萜内酯戈亚泽内酯(主要代谢产物)进行定量。在小鼠氧嗪酸钾诱导的高尿酸血症实验模型、肝黄嘌呤氧化酶(XOD)抑制实验以及角叉菜胶诱导的小鼠足跖肿胀实验中,测定灯笼草乙醇提取物和戈亚泽内酯的体内抗高尿酸血症和抗炎作用。

结果

建立了一种HPLC方法,以0.01%(v/v)乙酸水溶液和含0.01%(v/v)乙酸的乙腈为流动相,在梯度系统中,以香豆素为内标,在270nm处进行DAD检测。验证参数显示在10.0 - 150.0µg/ml范围内呈线性,日内和日间精密度范围为0.61 - 3.82。日内和日间分析的准确度值在87.58 - 100.95%之间。EA的戈亚泽内酯含量最高。在注射角叉菜胶后的第三至第六小时,所有提取物125mg/kg剂量的处理均能减轻水肿。戈亚泽内酯(10mg/kg)在第二小时的实验中显示出足跖肿胀显著减轻。这种倍半萜内酯比提取物更具活性,且呈现出与吲哚美辛相似的效果。与高尿酸血症对照组相比,ES、EA和EP(125mg/kg)以及戈亚泽内酯(10mg/kg)的处理降低了血清尿酸水平,并能够抑制肝XOD活性。ES、EA、EP和戈亚泽内酯发挥其抗高尿酸血症作用的机制之一是抑制肝XOD活性。戈亚泽内酯被确定为ES、EA、EW和EP中存在的主要化合物,并且被证明是乙醇提取物抗炎和抗高尿酸血症作用的化学成分之一。

结论

灯笼草乙醇提取物的抗炎和抗高尿酸血症活性并未受到整个季节中戈亚泽内酯含量变化的成比例影响。证实了戈亚泽内酯参与了灯笼草提取物的体内抗炎和抗高尿酸血症活性,以及其他成分参与这些作用的可能性。本研究表明,灯笼草地上部分可在任何季节采集用作抗炎剂。对于高尿酸血症的应用,最佳采集季节是夏季、秋季和春季。灯笼草乙醇提取物和戈亚泽内酯可被认为是治疗炎症、高尿酸血症和痛风的有前景的药物。

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