Evaluation of Rhamnetin as an Inhibitor of the Pharmacological Effect of Secretory Phospholipase A2
Evaluation of Rhamnetin as an Inhibitor of the Pharmacological Effect of Secretory Phospholipase A2
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DOI：
10.3390/molecules22091441
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发表时间：
2017-09-01
期刊：
影响因子：
4.6
通讯作者：
Toyama, Marcos Hikari
中科院分区：
文献类型：
--
作者：
Belchor, Mariana Novo;Gaeta, Henrique Hessel;Toyama, Marcos Hikari
鼠李素 (Rhm)、3-O-甲基槲皮素 (3MQ) 和鼠李素 (Rhz) 是槲皮素的甲基化衍生物，常见于水果和蔬菜中，具有抗氧化和抗炎特性。磷脂酶 A2 (PLA2) 在急性炎症过程中发挥多种重要作用；因此，除了评估肌酸激酶（CK）水平和细胞毒性之外，本研究还旨在研究能够抑制这种酶的新化合物。将甲基化槲皮素与槲皮素 (Q) 进行比较，并与来自白腹草的分泌性 PLA2 (sPLA2) 一起孵育，以确定其抑制活性。使用与槲皮素一起孵育的 J774 细胞谱系进行细胞毒性研究。对瑞士雌性小鼠进行体内测试，以评估降低爪水肿的潜力和化合物的 CK 水平。使用圆二色性 (CD) 对 sPLA2 进行结构修饰。尽管 Q 和 Rhz 显示出更大的酶抑制潜力，但观察到高 CK。 Rhm 表现出 sPLA2 抑制潜力，无毒性，并且显着地降低了 CK 水平。 Rhm C 环上 3OH 的存在可能有助于其抗炎和对 sPLA2 的酶抑制，而 A 环的甲基化可能会增加 sPLA2 诱导的细胞活力和降低 CK 水平。这些结果表明，RHM 可以作为天然化合物用于开发新型抗炎药物。
Rhamnetin (Rhm), 3-O-methylquercetin (3MQ), and Rhamnazin (Rhz) are methylated derivatives of quercetin commonly found in fruits and vegetables that possess antioxidant and anti-inflammatory properties. Phospholipase A2 (PLA2) displays several important roles during acute inflammation; therefore, this study aimed at investigating new compounds able to inhibit this enzyme, besides evaluating creatine kinase (CK) levels and citotoxicity. Methylated quercetins were compared with quercetin (Q) and were incubated with secretory PLA2 (sPLA2) from Bothrops jararacussu to determine their inhibitory activity. Cytotoxic studies were performed by using the J774 cell lineage incubated with quercertins. In vivo tests were performed with Swiss female mice to evaluate decreasing paw edema potential and compounds' CK levels. Structural modifications on sPLA2 were made with circular dichroism (CD). Despite Q and Rhz showing greater enzymatic inhibitory potential, high CK was observed. Rhm exhibited sPLA2 inhibitory potential, no toxicity and, remarkably, it decreased CK levels. The presence of 3OH on the C-ring of Rhm may contribute to both its anti-inflammatory and enzymatic inhibition of sPLA2, and the methylation of ring A may provide the increase in cell viability and low CK level induced by sPLA2. These results showed that Rhm can be a candidate as a natural compound for the development of new anti-inflammatory drugs.