Isolation and characterization of ellagic acid derivatives isolated from Casearia sylvestris SW aqueous extract with anti-PLA2 activity
Isolation and characterization of ellagic acid derivatives isolated from Casearia sylvestris SW aqueous extract with anti-PLA2 activity
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DOI：
10.1016/j.toxicon.2008.07.011
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发表时间：
2008-11-01
期刊：
影响因子：
2.8
通讯作者：
Marangoni, Sergio
中科院分区：
文献类型：
--
作者：
Da Silva, Saulo L.;Calgarotto, Andrana K.;Marangoni, Sergio
Casearia sylvestris SW（Flacourtiaceae）在民间医学（巴西和所有拉丁美洲）中用于治疗几种病理过程，如炎症，癌症，微生物感染和蛇咬伤。研究表明，樟子松水提物对蛇毒（或磷脂酶A（2））的多种毒性作用均有抑制作用，其中以棘头蛇属（Bothrops genus）蛇毒作用最强。抑制酶活性和肌毒活性，减少水肿形成，提高注射致死量的肉毒毒素的大鼠的存活率，是其抑制作用的一部分。本研究从樟子松（C sylvestris）的水提物中分离、鉴定了4种鞣花酸衍生物，并测试了它们对Bothrops jararacussu总毒和PLA（2）（Asp 49 BthTX-Ⅱ）的作用。经分离得到下列化合物：鞣花酸（A），3 ′-O-甲基鞣花酸（B），3，3 ′-二-O-甲基鞣花酸（C），3-O-甲基-3 ′，4 ′-亚甲二氧基鞣花酸（D）。酶活性的抑制常数（Ki）以及在致水肿和肌毒性活性中发现的IC 50值表明鞣花酸是这些活性的最佳抑制剂，而化合物C和D是抑制这些相同作用的能力最低的物质。我们的结果表明，在3位或3'位（化合物A和B）存在羟基增加了这些衍生物抑制这些毒性作用的能力。然而，在3位或3'位的新乙氧基的存在降低了化合物C和D抑制所研究的所有毒性作用的能力，但没有完全抑制化合物C和D抑制所研究的所有毒性作用的能力。(c)2008爱思唯尔有限公司保留所有权利。
The Casearia sylvestris SW (Flacourtiaceae) is utilized in folk medicine (Brazil and all Latin American) to treat several pathologic processes as inflammation, cancer, microbial infection and snake bites. Studies showed that C sylvestris aqueous extract can inhibit many toxic effects caused by snake venoms (or caused by phospholipase A(2) isolated) from different species, mainly of Bothrops genus. Inhibition of enzymatic and myotoxic activities, decrease of edema formation and increase of the survival rate of rats injected with lethal doses of bothropic venoms are some toxic effects inhibited by C sylvestris. In this study, four ellagic acid derivatives from aqueous extracts of C sylvestris were isolated, characterized, and tested against effects from both total venom and PLA(2) (Asp 49 BthTX-II) from the venom of Bothrops jararacussu. The isolated compounds were as follows: ellagic acid (A), 3'-O-methyl ellagic acid (B), 3,3'-di-O-methyl ellagic acid (C), 3-O-methyl-3', 4'-methylenedioxy ellagic acid (D). The inhibition constant values (Ki) for enzymatic activity, as well the IC50 values found in the edematogenic and myotoxic activities, indicate that the ellagic acid is the best inhibitor of these activities, while compounds C and D are the substances with lowest capacity on inhibiting these same effects. Our results show that the presence of hydroxyls at position 3 or 3' (compounds A and B) increases the capacity of these derivatives on inhibiting these toxic effects. However, the presence of nuethoxyl groups at position 3 or 3' reduced, but did not completely inhibit the capacity of compounds C and D on inhibiting all the toxic effects studied. (c) 2008 Elsevier Ltd. All rights reserved.