Rabelo Thallita Kelly, Guimarães Adriana Gibara, Oliveira Marlange Almeida, Gasparotto Juciano, Serafini Mairim Russo, de Souza Araújo Adriano Antunes, Quintans-Júnior Lucindo José, Moreira José Cláudio Fonseca, Gelain Daniel Pens
Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, ICBS, UFRGS, Porto Alegre, RS, Brazil.
Departamento de Educação em Saúde, UFS, Lagarto, SE, Brazil.
Int Immunopharmacol. 2016 Oct;39:97-105. doi: 10.1016/j.intimp.2016.07.016. Epub 2016 Jul 25.
Shikimic acid (SA) is present in a wide variety of plants and microorganisms used in traditional and folk medicine and also is an essential starting material for the synthesis of the antiviral drug Oseltamivir (Tamiflu®). Some pharmacological actions observed in SA-enriched products include antioxidant and anti-inflammatory activities. Here, we investigated the anti-inflammatory and antinociceptive actions of isolated SA.
RAW 264.7 macrophage cells were treated with bacterial LPS (1μg/mL) and the effect of SA on the modulation of cell viability, nitric oxide (NO) production, TNF-α, and IL-1β content and MAPK (ERK1/2 and p38) activation was evaluated. Besides, the anti-hyperalgesic actions of SA on in vivo model of mechanical hyperalgesia induced by carrageenan (CG), dopamine (DA), TNF-α and prostaglandin (PGE2) were assessed.
In RAW 264.7 cells, SA suppressed LPS-induced decrease in cell viability and nitrite accumulation to control values and inhibited up-regulation of TNF-α (65%) and IL-1β (39%). These effects may be mediated at least in part by inhibition of LPS-induced ERK 1/2 (22%) and p38 (17%) phosphorylation. In mice, SA at 50, 100, and 200mg/kg decreased formalin-induced nociceptive behavior (around 50%) and inhibited the inflammatory nociception induced by TNF-α and PGE2 (50 to 75% each). Moreover, SA (100 and 200mg/kg) significantly attenuated the mechanical hyperalgesia induced by CG and DA (25 to 40% each).
These results indicate that SA presents anti-inflammatory actions with potential for development of drugs to treat pro-inflammatory and painful conditions.
莽草酸（SA）存在于传统和民间医学中使用的多种植物和微生物中，也是合成抗病毒药物奥司他韦（达菲®）的重要起始原料。在富含SA的产品中观察到的一些药理作用包括抗氧化和抗炎活性。在此，我们研究了分离出的SA的抗炎和镇痛作用。
用细菌脂多糖（1μg/mL）处理RAW 264.7巨噬细胞，评估SA对细胞活力调节、一氧化氮（NO）产生、肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）含量以及丝裂原活化蛋白激酶（MAPK，细胞外信号调节激酶1/2（ERK1/2）和p38）激活的影响。此外，评估了SA对角叉菜胶（CG）、多巴胺（DA）、TNF-α和前列腺素（PGE2）诱导的机械性痛觉过敏体内模型的抗痛觉过敏作用。
在RAW 264.7细胞中，SA抑制了脂多糖诱导的细胞活力下降和亚硝酸盐积累至对照值，并抑制了TNF-α（65%）和IL-1β（39%）的上调。这些作用可能至少部分是通过抑制脂多糖诱导的ERK 1/2（22%）和p38（17%）磷酸化介导的。在小鼠中，50、100和200mg/kg的SA降低了福尔马林诱导的伤害性反应（约50%），并抑制了TNF-α和PGE2诱导的炎性痛觉过敏（各50%至75%）。此外，SA（100和200mg/kg）显著减轻了CG和DA诱导的机械性痛觉过敏（各25%至40%）。
这些结果表明，SA具有抗炎作用，有开发治疗炎症性和疼痛性疾病药物的潜力。
