Pharmacological mechanisms underlying the anti-ulcer activity of methanol extract and canthin-6-one of Simaba ferruginea A. St-Hil. in animal models
Pharmacological mechanisms underlying the anti-ulcer activity of methanol extract and canthin-6-one of Simaba ferruginea A. St-Hil. in animal models
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DOI：
10.1016/j.jep.2011.01.009
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发表时间：
2011-04-12
影响因子：
5.4
通讯作者：
de Oliveira Martins, Domingos Tabajara
中科院分区：
文献类型：
--
作者：
de Souza Almeida, Elisangela Saturnino;Cechinel Filho, Valdir;de Oliveira Martins, Domingos Tabajara
相关性：Simaba ferrugulae A.圣希尔（Simaroubaceae）是巴西Cerrado的典型亚灌木，其根茎普遍用作治疗胃溃疡、腹泻和发热的输液或汤剂。研究目的：评价Simaba ferrugelae的甲醇提取物及其生物碱canthin-6-one的抗溃疡作用的药理学机制。材料和方法：用甲醇浸提铁马豆根茎，得到甲醇提取物（MESf），从中得到氯仿级分。对Canthin-6-one生物碱（Cant）进行纯化，然后从氯仿级分（CFSf）中分离。通过HPLC鉴定分离的Cant。分别在小鼠和大鼠中使用乙醇和吲哚美辛诱导的溃疡模型测定抗溃疡测定。为了确定MESf和Cant的可能作用机制，在抗溃疡剂处理之前用L-NAME预处理动物，并确定溃疡诱导和一氧化氮（NO）水平，以评估NO参与胃保护作用。丙二醛（MDA）、髓过氧化物酶（MPO）、促炎细胞因子：白细胞介素8（IL-8）和肿瘤坏死因子-α的测定还根据先前描述的方法进行肿瘤坏死因子（TNF-α）和前列腺素E-2（PGE（2））的测定。结果表明，MESf和Cant在乙醇中的抗溃疡作用，诱导的溃疡部分通过增加保护性内源性NO的产生来介导，因为在用L-NAME预处理的动物中MESf和Cant的抗溃疡活性降低。在吲哚美辛诱导的溃疡中，MESf和Cant预处理显示胃组织中MPO和MDA水平降低，从而表明抗氧化机制参与胃保护作用。Cant也能降低消炎痛溃疡大鼠血浆IL-8水平，但MESf不能，表明抑制这种细胞因子有助于Cant的胃保护作用。然而，MESf和Cant对粘膜PGE（2）水平没有影响，表明这些药物的胃保护作用不依赖于PGE（2）的调节。本研究中使用MESf和Cant获得的结果增加了对其抗溃疡作用模式所涉及的药理学机制的见解。结果表明，Cant是造成这些影响的化合物之一。这些发现对于未来开发强效、安全和有效的抗溃疡剂具有极其重要的意义。MESf和Cant在胃保护中的功效表明，Simaba ferrugulose可能是一种有前途的抗溃疡草药，此外还证实了这种植物在本研究中对胃溃疡模型的广泛使用。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Relevance: Simaba ferruginea A. St-Hil. (Simaroubaceae) is a subshrub typical of the Brazilian Cerrado, whose rhizomes are popularly used as infusion or decoction for the treatment of gastric ulcers, diarrhea and fever.Aim of the study: To evaluate the pharmacological mechanism(s) of action of the antiulcer effects of the methanol extract of Simaba ferruginea and its alkaloid canthin-6-one.Materials and methods: Rhizome of Simaba ferruginea was macerated with methanol to obtain the methanol extract (MESf) from which was obtained, the chloroform fraction. Canthin-6-one alkaloid (Cant) was purified and then isolated from the chloroform fraction (CFSf). The isolated Cant was identified by HPLC. Anti-ulcer assays were determined using ethanol and indomethacin-induced ulcer models in mice and rats respectively. In order to determine the probable mechanisms of actions of MESf and Cant animals were pretreated with L-NAME prior to anti-ulcer agent treatments and ulcer induction and nitric oxide (NO) level determined in order to assess NO involvement in the gastroprotective effects. Assays of malondialdehyde (MDA), myeloperoxidase (MPO), pro-inflammatory cytokines: interleukin 8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E-2 (PGE(2)) were also carried out according to previously described methods.Results: The results indicate that the antiulcerogenic effects of MESf and Cant in ethanol-induced ulcer is mediated in part through increase in the production of protective endogenous NO as the antiulcerogenic activity of MESf and Cant was reduced in animals pre-treated with L-NAME. In indomethacin-induced ulcer pre-treatment with MESf and Cant showed reduction in the levels of MPO and MDA in the gastric tissue, thus indicating the participation of the antioxidant mechanisms on the gastroprotective effects. The plasma levels of IL-8 in ulcerated rats with indomethacin were also reduced by Cant, but not by MESf, indicating that inhibition of this cytokine contributes to the gastroprotective effect of Cant However MESf and Cant had no effect on the mucosal membrane levels of PGE(2), indicating that the gastroprotective effects of these agents is independent of PGE(2) modulation.Conclusion: The results obtained in this study with MESf and Cant added insights into the pharmacological mechanisms involved in their mode of antiulcer action. The results indicate that Cant is one of the compounds responsible for these effects. Such findings are of extreme importance in the strive for future development of potent, safer and effective antiulcer agent. The efficacy of MESf and Cant in gastroprotection shows that Simaba ferruginea might be a promising antiulcer herbal medicine, in addition to confirming the popular use of this plant against gastric ulcer models utilised in this study. (C) 2011 Elsevier Ireland Ltd. All rights reserved.