Correlation of the inhibitory activity of phospholipase A2 snake venom and the antioxidant activity of Colombian plant extracts

Abstract

RESUMO:Veneno de cobra continua a ser um problema importante de saúde em muitos países da América Latina. Apesar dos avanços na terapia antiveneno, os efeitos locais causados por fosfolipases A 2 miotóxica (PLA 2 ) presentes no veneno, ainda persistem. Em busca de alternativas para antagonizar a atividade da PLA 2 do veneno de Bothrops asper, foram selecionados 36 extratos pertencentes a dezessete famílias de plantas vasculares e briófitas. Uma inibição significativa da atividade enzimática de PLA 2 presente no veneno de B. asper foi observada em onze extratos. Além disso, a atividade antioxidante dos extratos foi avaliada. Os resultados evidenciaram uma correlação estatisticamente significativa entre os extratos com ação inibitória contra a PLA 2 e aqueles com atividade antioxidante. Também, a quantidade de fenóis foi avaliada e foi encontrada uma relação entre a atividade biológica e a presença dessas substâncias. Nove extratos foram testados contra uma fração do veneno rico em PLA 2 básica (Fx-V B. asper), resultando em um efeito inibitório na atividade desta fração da PLA 2 na faixa de 30-80%. Esta atividade foi apoiada pela inibição que esses extratos apresentaram na citotoxicidade causada pelo Fx-V B. asper sobre mioblastos C2C12 de músculo esquelético de murino. Os resultados podem indicar a minimização dos esforços na busca de inibidores da PLA 2 , com foco nas amostras com propriedades antioxidantes conhecidas.Unitermos: fosfolipase A 2 , veneno de cobra, Bothrops asper, extratos de plantas, antioxidantes, DPPH.ABSTRACT: Snakebite continues to be a significant health problem in many countries of Latin America. Even though, there has been an improvement in the antivenom therapy, the local effects caused by myotoxic phospholipases A 2 (PLA 2 ) present in the venoms, still persist. In search for alternatives to antagonize the PLA 2 activity of Bothrops asper's venom, 36 extracts belonging to seventeen families of vascular plants and bryophytes were screened. A significant inhibition of the enzymatic activity of PLA 2 present in B. asper's whole venom was seen in eleven of these extracts. In addition, the antioxidant activity of all the extracts was evaluated. The results evidenced a significant statistical correlation between extracts with an inhibitory effect against PLA 2 and those with an antioxidant activity. Moreover, the amount of phenols was quantified finding a relationship between the bioactivity and the presence of these compounds. Nine extracts were screened against a fraction of the venom rich in basic PLA 2 (Fx-V B. asper), exhibiting an inhibitory effect on PLA 2 activity of this fraction in a range of 30-80%. This activity was supported by the inhibition that these extracts presented on the cytotoxicity caused by Fx-V B. asper on murine skeletal muscle C2C12 myoblasts. The results obtained, could point to minimize efforts in the search of PLA 2 inhibitors by focusing in samples with known antioxidant properties.

CHARACTERIZATION OF THE MOST PROMISING FRACTION OF Swietenia macrophylla ACTIVE AGAINST MYOTOXIC PHOSPHOLIPASES A2 : IDENTIFICATION OF CATECHIN AS ONE OF THE ACTIVE COMPOUNDS

“…Fraction F5 was also evaluated against PLA 2 s present in B. asper venom, and dose-dependent activity was exhibited. These results are comparable to those reported by Pereañez et al [16], in which an inhibition level of 59.3 ± 3.5% was found for the crude extract of the leaves of S. macrophylla. Similarly, the total inhibition of the cytotoxic activity caused by a Lys49 PLA 2 , by fraction F5 was evidenced.…”

“…Likewise, different types of plantderived compounds, such as flavonoids, coumarins, and other phenolic metabolites, have shown promise in neutralizing the PLA 2 effects [12][13][14][15]. The species Swietenia macrophylla King (Meliaceae), also known as mahogany, was selected as a promising lead after screening thirty-six ethanolic leaf extracts, in a search for their neutralizing activity against Bothrops asper venom and PLA 2 isolated from the venom of Crotalus durissus cumanensis [16,17]. The tree is native to tropical America [18] and numerous biological properties have been reported for its leaves and twigs, including antidiabetic, tumor inhibition, anti-inflammatory, antifungal, antimalarial and insect antifeedant activities [19].…”

ACUTE ORAL TOXICITY FROM A FRACTION RICH IN PHENOLIC COMPOUNDS FROM THE LEAF EXTRACT OF Swietenia macrophylla KING IN A MURINE MODEL

“…In addition, this extract did not show toxicity to cultured muscle cells. In this same study, it was reported that polar fractions derived from the leaf ethanolic extract were rich in phenolic compounds (12,13), which are suggested to be involved in the inhibitory activity of phospholipase A 2 as previously described (14). In a subsequent study were a bioassay-guided fractionation was carried out with the ethanolic leaf extract of S. macrophylla, the activity of several fractions against PLA 2 s from B. atrox, B. asper and C. durissus cumanensis in vitro and in vivo were evaluated.…”

Medicinal Plants for the Treatment of Local Tissue Damage Induced by Snake Venoms: An Overview from Traditional Use to Pharmacological Evidence

“…In fact, many medicinal plants with antiophidic activity also possess significant anti-inflammatory activity in vivo [ 83 , 96 , 107 – 110 ]. Following the same reasoning, some plants with antioxidant activity also possess significant antiophidic effects [ 95 , 96 , 104 , 111 ]. In fact, some authors suggest that molecules with antioxidant and/or anti-inflammatory effects could be interesting along with antivenom therapy, helping to reduce the occurrence of secondary/long term complication due to snakebites [ 112 ].…”