Januário Ana H, Santos Simone L, Marcussi Silvana, Mazzi Maurício V, Pietro Rosemeire C L R, Sato Daisy N, Ellena Javier, Sampaio Suely V, França Suzelei C, Soares Andreimar M
Unidade de Biotecnologia, Universidade de Ribeirão Preto, UNAERP, Ribeirão Preto-SP, Brazil.
Chem Biol Interact. 2004 Dec 7;150(3):243-51. doi: 10.1016/j.cbi.2004.09.016.
Many plants are used in traditional medicine as active agents against various effects induced by snakebite. Few attempts have been made however to identify the nature of plant natural products with anti-ophidian properties. Baccharis trimera (Less) DC (Asteraceae), known in Brazil as carqueja, has been popularly used to treat liver diseases, rheumatism, diabetes, as well as digestive, hepatic and renal disorders. The active component was identified as 7alpha-hydroxy-3,13-clerodadiene-16,15:18,19-diolide, C20H28O5, (clerodane diterpenoid, Bt-CD). We report now the anti-proteolytic and anti-hemorrhagic properties against snake venoms of a Bt-CD inhibitor from B. trimera. Bt-CD exhibited full inhibition of hemorrhage and proteolytic activity caused by Bothrops snake venoms. The inhibitor was able to neutralize the hemorrhagic, fibrinogenolytic and caseinolytic activities of class P-I and III metalloproteases isolated from B. neuwiedi and B. jararacussu venoms. No inhibition of the coagulant activity was observed. Bt-CD also partially inhibited the edema induced by other crude venoms, metalloproteases, basic and acidic phospholipases A2. To further elucidate the inhibitory specificity of Bt-CD against metalloproteases isolated from snake venoms, a deeper understanding of its structure and function is necessary. Furthermore, the potential use of these inhibitors to complement anti-venom as an alternative treatment of snakebite envenomations needs to be evaluated in future studies.
许多植物在传统医学中被用作对抗蛇咬伤所引发的各种效应的活性剂。然而，几乎没有人尝试去鉴定具有抗蛇类特性的植物天然产物的性质。巴西称为carqueja的三裂叶酒神菊（Baccharis trimera (Less) DC，菊科），一直被广泛用于治疗肝脏疾病、风湿病、糖尿病以及消化、肝脏和肾脏疾病。其活性成分被鉴定为7α-羟基-3,13-克罗烷二烯-16,15:18,19-二内酯，C20H28O5，（克罗烷二萜，Bt-CD）。我们现在报告一种来自三裂叶酒神菊的Bt-CD抑制剂对蛇毒的抗蛋白水解和抗出血特性。Bt-CD对具窍蝮蛇属蛇毒引起的出血和蛋白水解活性表现出完全抑制作用。该抑制剂能够中和从新维氏具窍蝮蛇和巴西具窍蝮蛇毒液中分离出的P-I和III类金属蛋白酶的出血、纤维蛋白原溶解和酪蛋白溶解活性。未观察到对凝血活性的抑制作用。Bt-CD还部分抑制了其他粗毒液、金属蛋白酶、碱性和酸性磷脂酶A2诱导的水肿。为了进一步阐明Bt-CD对从蛇毒中分离出的金属蛋白酶的抑制特异性，有必要更深入地了解其结构和功能。此外，这些抑制剂作为抗蛇毒血清的补充用于替代治疗蛇咬伤中毒的潜在用途需要在未来的研究中进行评估。
