Quercetin as an inhibitor of snake venom secretory phospholipase A2
Quercetin as an inhibitor of snake venom secretory phospholipase A2
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DOI：
10.1016/j.cbi.2010.10.016
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发表时间：
2011-01-15
影响因子：
5.1
通讯作者：
Toyama, Marcos Hikari
中科院分区：
文献类型：
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作者：
Cotrim, Camila Aparecida;Buzzo de Oliveira, Simone Cristina;Toyama, Marcos Hikari
黄酮类化合物是从植物提取物中分离出来的多酚类化合物，具有抗炎、抗癌和心血管保护作用，近几十年来被广泛应用于医药领域。在本研究中，我们研究了黄酮类槲皮素对硬骨鱼分泌型磷脂酶A2(SPLA2)的影响，sPLA2是参与花生四烯酸从磷脂膜中释放的重要蛋白质。用槲皮素对蛋白质进行化学修饰，通过圆二色谱证明蛋白质的二级结构发生了改变。此外，Quercetin能够抑制sPLA2的酶活性和某些药理活性，包括其抗菌活性、诱导血小板聚集的能力和肌肉毒性约40%，但不能降低sPLA2的炎症和神经毒性活性。这些结果表明，蛋白质中存在两个药理位点，一个与酶位点相关，另一个与酶位点不同。我们还进行了分子对接，以更好地了解Quercetin和sPLA2之间可能的相互作用。我们的对接数据表明存在氢键、极性相互作用和疏水相互作用，这表明其他具有类似结构的黄酮类化合物可以与sPLA2结合。有必要进一步研究类黄酮类化合物作为sPLA2抑制剂的潜在用途。(C)2010爱思唯尔爱尔兰有限公司。保留所有权利。
As polyphenolic compounds isolated from plants extracts, flavonoids have been applied to various pharmaceutical uses in recent decades due to their anti-inflammatory, cancer preventive, and cardiovascular protective activities. In this study, we evaluated the effects of the flavonoid quercetin on Crotalus durissus terrificus secretory phospholipase A2 (sPLA2), an important protein involved in the release of arachidonic acid from phospholipid membranes. The protein was chemically modified by treatment with quercetin, which resulted in modifications in the secondary structure as evidenced through circular dichroism. In addition, quercetin was able to inhibit the enzymatic activity and some pharmacological activities of sPLA2, including its antibacterial activity, its ability to induce platelet aggregation, and its myotoxicity by approximately 40%, but was not able to reduce the inflammatory and neurotoxic activities of sPLA2. These results suggest the existence of two pharmacological sites in the protein, one that is correlated with the enzymatic site and another that is distinct from it. We also performed molecular docking to better understand the possible interactions between quercetin and sPLA2. Our docking data showed the existence of hydrogen-bonded, polar interactions and hydrophobic interactions, suggesting that other flavonoids with similar structures could bind to sPLA2. Further research is warranted to investigate the potential use of flavonoids as sPLA2 inhibitors. (C) 2010 Elsevier Ireland Ltd. All rights reserved.