Da Silva Saulo L, Calgarotto Andrana K, Chaar Jamal S, Marangoni Sérgio
Campus Avançado de Divinópolis, Universidade Fed. de São João Del Rei, CEP 35501-296 Divinópolis, MG, Brazil.
Toxicon. 2008 Nov;52(6):655-66. doi: 10.1016/j.toxicon.2008.07.011. Epub 2008 Aug 5.
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 IC(50) 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 methoxyl 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.
野鸦椿（大风子科）在民间医学（巴西及所有拉丁美洲国家）中用于治疗多种病理过程，如炎症、癌症、微生物感染和蛇咬伤。研究表明，野鸦椿水提取物可抑制多种不同种类蛇毒（或分离出的磷脂酶A₂）引起的许多毒性作用，主要是矛头蝮属蛇毒。野鸦椿可抑制的毒性作用包括酶活性和肌毒性活性的抑制、水肿形成的减少以及注射致死剂量的矛头蝮蛇毒的大鼠存活率的提高。在本研究中，从野鸦椿水提取物中分离出四种鞣花酸衍生物，进行了表征，并测试了其对矛头蝮蛇毒总毒液和PLA₂（Asp 49 BthTX-II）作用的影响。分离出的化合物如下：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）值以及在致水肿和肌毒性活性中发现的IC₅₀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能力最低的物质。我们的结果表明，3位或3'位存在羟基（化合物A和B）会增加这些衍生物抑制这些毒性作用的能力。然而，3位或3'位存在甲氧基会降低但并未完全抑制化合物C和D抑制所有所研究毒性作用的能力。
