Antiplasmodial activity of Punica granatum L. fruit rind
Antiplasmodial activity of Punica granatum L. fruit rind
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DOI：
10.1016/j.jep.2009.06.025
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发表时间：
2009-09-07
影响因子：
5.4
通讯作者：
Bosisio, Enrica
中科院分区：
文献类型：
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作者：
Dell'Agli, Mario;Galli, Germana V.;Bosisio, Enrica
研究目的：太阳晒干的石榴属植物（Punica granatum L., Punicaceae）（Pg）的未成熟果皮目前在印度奥里萨邦用作草药制剂（OMARIA），用于治疗和预防疟疾。本研究的目的是：(1)在体外评估抗疟植物的甲醇提取物、单宁富集部分和化合物/代谢物的抗疟原虫活性，(2)估计Pg提取物的疗效，(3)探索抗疟原虫化合物的作用机制。还研究了鞣花单宁代谢产物尿石素的抗疟原虫活性。材料与方法：体外研究采用氯喹敏感（D10）和耐药（W2）菌株，体内研究采用啮齿动物疟疾模型伯氏疟原虫- balb /c小鼠。利用重组plasmepins 2和4研究了Pg化合物对疟原虫血红蛋白代谢的干扰。结果：Pg甲醇提取物（Pg- meoh）对D10和W2菌株的体外抑制作用IC50分别为4.5和2.8 μ g/ml。该活性与富含单宁（Pg-FET， IC50分别为2.9和1.5 μ g/ml）的部位有关，其中可以鉴定出果蕊苷（29.1%）、果蕊苷、鞣花酸（13.4%）及其苷。Pg-MeOH提取物和Pg-FET对Plasmepsin 2均有抑制作用（IC50分别为7.3和3.0 μ g/ml），这可以部分解释其抗寄生虫作用。相反，尿石素是无活性的。Pg-MeOH提取物和Pg-FET在小鼠模型中均无体内药效。结论：体外研究支持Pg作为抗疟药物的应用。对体内阴性结果的可能解释进行了讨论。2009爱思唯尔爱尔兰有限公司版权所有。
Aim of the study: Sun-dried rind of the immature fruit of Punica granatum L. (Punicaceae)(Pg) is presently used as a herbal formulation (OMARIA) in Orissa, India, for the therapy and prophylaxis of malaria. The aims of this study were (i) to assess in vitro the antiplasmodial activity of the methanolic extract, of a tannin enriched fraction and of compounds/metabolites of the antimalarial plant, (ii) to estimate the curative efficacy of the Pg extracts and (iii) to explore the mechanism of action of the antiplasmodial compounds. Urolithins, the ellagitannin metabolites, were also investigated for antiplasmodial activity.Materials and methods: Chloroquine-susceptible (D10) and -resistant (W2) strains of Pf were used for in vitro studies and the rodent malaria model Plasmodium berghei-BALB/c mice was used for in vivo assessments. Recombinant plasmepsins 2 and 4 were used to investigate the interference of Pg compounds with the metabolism of haemoglobin by malaria parasites.Results: The Pg methanolic extract (Pg-MeOH) inhibited parasite growth in vitro with a IC50 of 4.5 and 2.8 mu g/ml, for D10 and W2 strain, respectively. The activity was found to be associated to the fraction enriched with tannins (Pg-FET, IC50 2.9 and 1.5 mu g/ml) in which punicalagins (29.1%), punicalins, ellagic acid (13.4%) and its glycoside could be identified. Plasmepsin 2 was inhibited by Pg-MeOH extract and by Pg-FET (IC50 7.3 and 3.0 mu g/ml), which could partly explain the antiparasitic effect. On the contrary, urolithins were inactive. Both Pg-MeOH extract and Pg-FET did not show any in vivo efficacy in the murine model.Conclusions: The in vitro studies support the use of Pg as antimalarial remedy. Possible explanations for the negative in vivo results are discussed. (C) 2009 Elsevier Ireland Ltd. All rights reserved.