Departamento de Bioquímica, Escuela de Química Biológica, Facultad de Ciencias Químicas y Farmacia, Universidad de San Carlos de Guatemala, Guatemala.
Departamento de Bioquímica, Escuela de Química Biológica, Facultad de Ciencias Químicas y Farmacia, Universidad de San Carlos de Guatemala, Guatemala.
J Ethnopharmacol. 2022 Jan 30;283:114710. doi: 10.1016/j.jep.2021.114710. Epub 2021 Oct 6.
Snakebite envenoming is a public health problem of high impact in Central America. Bothrops asper, known as barba amarilla, terciopelo, and equis, is the snake species responsible for most snakebites in Central America. In this region, there is a long-standing tradition on the use of plants in the management of snakebites, especially in indigenous communities. Ethnomedical use of Eryngium foetidum L., Neurolaena lobata (L.) Cass. and Pimenta dioica (L.) Merr. to treat snakebite envenoming has been reported in Belice, Guatemala, Nicaragua, and Costa Rica. Extracts of the leaves of these plants have shown anti-venom activities in in vitro assays in previous studies.
To assess the ability of organic fractions from these three plants to inhibit enzymatic activities associated with toxicity of the venom of B. asper, and to study, by docking analysis, the interaction of metalloproteinase and phospholipases A (PLA) from B. asper venom with secondary metabolites previously described in these plants.
Organic fractions were obtained from these three plant species and their ability to neutralize proteolytic, PLA and in vitro coagulant activities of B. asper venom was assessed. A phytochemical analysis was carried out in these fractions. The interaction of secondary metabolites previously described in these plants with three toxins from B. asper venom (a metalloproteinase, a PLA and a PLA homologue) was investigated by docking analysis.
The inhibitory activity of plants was mainly concentrated in their polar fractions. Acetonic fraction from P. dioica was the most active against PLA activity, while the acetonic fraction of E. foetidum completely inhibited the proteolytic activity of the venom. Coagulant activity was partially inhibited only by the acetone and ethyl acetate fractions of P. dioica. Phytochemical analysis of the most bioactive fractions identified flavonoids, saponins, essential oils, coumarins, alkaloids, tannins and sesquiterpene lactones. Docking analysis revealed high affinity interactions of several secondary metabolites of these plants with residues in the vicinity of the catalytic site of these enzymes and, in the case of PLA homologue myotoxin II, in the hydrophobic channel.
Various fractions from these plants have inhibitory activity against enzymatic actions of B. asper venom which are directly associated with toxicological effects. Docking analysis showed structural evidence of the interaction of secondary metabolites with three toxins. These observations provide support to the potential of these plants to inhibit relevant toxic components of this snake venom.
蛇咬伤中毒是中美洲一个具有高度公共卫生影响的问题。矛头蝮，又称黄吻矛头蝮、绒矛头蝮和马岛矛头蝮，是中美洲大多数蛇咬伤的罪魁祸首。在该地区，植物在蛇咬伤治疗中的应用有着悠久的传统，尤其是在土著社区。在伯利兹、危地马拉、尼加拉瓜和哥斯达黎加，人们曾报道过用皱叶酸模、大花奎藜和丁香治疗蛇咬伤中毒。在以前的研究中，这些植物的叶提取物在体外试验中显示出抗蛇毒活性。
评估这三种植物的有机部位抑制矛头蝮毒液相关毒性的酶活性的能力，并通过对接分析研究矛头蝮毒液中的金属蛋白酶和磷脂酶 A（PLA）与这些植物中先前描述的次生代谢物的相互作用。
从这三种植物中提取有机部位，并评估其对矛头蝮毒液的蛋白水解、PLA 和体外凝血活性的中和能力。对这些部位进行了植物化学分析。通过对接分析研究了这些植物中先前描述的次生代谢物与矛头蝮毒液中的三种毒素（一种金属蛋白酶、一种 PLA 和一种 PLA 同源物）的相互作用。
植物的抑制活性主要集中在极性部位。丁香的丙酮部位对 PLA 活性的抑制作用最强，而皱叶酸模的丙酮部位完全抑制了毒液的蛋白水解活性。只有丁香的丙酮和乙酸乙酯部位部分抑制了凝血活性。最具生物活性的部位的植物化学分析鉴定出黄酮类、皂苷、挥发油、香豆素、生物碱、单宁和倍半萜内酯。对接分析显示，这些植物的几种次生代谢物与这些酶的催化位点附近的残基以及 PLA 同系物肌毒素 II 的疏水性通道具有高亲和力相互作用。
这些植物的各种部位对矛头蝮毒液的酶促作用具有抑制活性，这些作用与毒理学效应直接相关。对接分析显示了次生代谢物与三种毒素相互作用的结构证据。这些观察结果为这些植物抑制这种蛇毒的相关毒性成分提供了支持。
