Silva Rosa H M, Lima Nathália de Fátima M, Lopes Alberto J O, Vasconcelos Cleydlenne C, de Mesquita José W C, de Mesquita Ludmilla S S, Lima Fernando C V M, Ribeiro Maria N de S, Ramos Ricardo M, Cartágenes Maria do Socorro de S, Garcia João B S
Experimental Study of Pain Laboratory, Department of Physiological Sciences, Federal University of MaranhãoSão Luís, Brazil.
Laboratory of Pharmacognosy, Department of Pharmacy, Federal University of MaranhãoSão Luís, Brazil.
Front Pharmacol. 2017 May 22;8:283. doi: 10.3389/fphar.2017.00283. eCollection 2017.
(L.) G. Mey. known vassourinha has antibacterial, antimalarial, hepatoprotective, antioxidative, analgesic, and anti-inflammatory, however, its antinociceptive action requires further studies. Aim of the study evaluated the antinociceptive activity of hydroalcoholic extract (EHBv) and ethyl acetate fraction (FAc) by and studies. assessment included the paw edema test, writhing test, formalin test and tail flick test. Wistar rats and Swiss mice were divided into 6 groups and given the following treatments oral: 0.9% NaCl control group (CTRL), 10 mg/kg memantine (MEM), 10 mg/kg indomethacin (INDO), 500 mg/kg EHBv (EHBv 500), 25 mg/kg FAc (FAc 25) and 50 mg/kg FAc (FAc 50). EHBv, FAc 25 and 50 treatments exhibited anti-edematous and peripheral antinociceptive effects. For assessment, compounds identified in FAc were subjected to molecular docking with COX-2, GluN1a and GluN2B. Ursolic acid (UA) was the compound with best affinity parameters (binding energy and inhibition constant) for COX-2, GluN1a, GluN2B, and was selected for further analysis with molecular dynamics (MD) simulations. In MD simulations, UA exhibited highly frequent interactions with residues Arg120 and Glu524 in the COX-2 active site and NMDA, whereby it might prevent COX-2 and NMDA receptor activation. Treatment with UA 10 mg/Kg showed peripheral and central antinociceptive effect. The antinociceptive effect of might be predominantly attributed to peripheral actions, including the participation of anti-inflammatory components. Ursolic acid is the main active component and seems to be a promising source of COX-2 inhibitors and NMDA receptor antagonists.
(L.) G. Mey. 已知的小叶锦葵具有抗菌、抗疟疾、肝脏保护、抗氧化、镇痛和抗炎作用，然而，其抗伤害感受作用需要进一步研究。本研究的目的是通过热板法和扭体法评估水醇提取物（EHBv）和乙酸乙酯馏分（FAc）的抗伤害感受活性。评估包括足爪水肿试验、扭体试验、福尔马林试验和甩尾试验。将Wistar大鼠和瑞士小鼠分为6组并给予以下口服治疗：0.9%氯化钠对照组（CTRL）、10 mg/kg美金刚（MEM）、10 mg/kg吲哚美辛（INDO）、500 mg/kg EHBv（EHBv 500）、25 mg/kg FAc（FAc 25）和50 mg/kg FAc（FAc 50）。EHBv、FAc 25和50处理表现出抗水肿和外周抗伤害感受作用。为了进行分子对接评估，将在FAc中鉴定出的化合物与COX-2、GluN1a和GluN2B进行分子对接。熊果酸（UA）是对COX-2、GluN1a、GluN2B具有最佳亲和力参数（结合能和抑制常数）的化合物，并被选择用于分子动力学（MD）模拟的进一步分析。在MD模拟中，UA在COX-2活性位点和NMDA中与残基Arg120和Glu524表现出高度频繁的相互作用，由此它可能阻止COX-2和NMDA受体激活。用10 mg/Kg UA处理表现出外周和中枢抗伤害感受作用。其抗伤害感受作用可能主要归因于外周作用，包括抗炎成分的参与。熊果酸是主要活性成分，似乎是一种有前景的COX-2抑制剂和NMDA受体拮抗剂来源。
