Laboratório de Farmacognosia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, (UFRGS), Porto Alegre, RS, Brazil.
Departamento de Bioquímica, UFRGS, Porto Alegre, RS, Brazil.
Comp Biochem Physiol C Toxicol Pharmacol. 2021 Jan;239:108874. doi: 10.1016/j.cbpc.2020.108874. Epub 2020 Aug 14.
Neuroinflammation has been associated to neurodegenerative disease development, with evidence suggesting that high levels of proinflammatory cytokines promote neuronal dysfunction and death. Therefore, it is necessary to study new compounds that may be used as adjuvant treatments of neurodegenerative diseases by attenuating the inflammatory response in the central nervous system (CNS). The aim of this study was to utilize the lipopolysaccharide (LPS) induction model of neuroinflammation to evaluate the modulation of inflammation by rosmarinic acid (RA) isolated from Blechnum brasiliense in adult zebrafish. First, we investigated the toxicity and antioxidant properties of fractionated B. brasiliense extract (ethyl acetate fraction- EAF) and the isolated RA in zebrafish embryos. Next, we developed a model of neuroinflammation induction by intraperitoneal (i.p.) injection of LPS to observe the RA modulation of proinflammatory cytokines. The median lethal concentration (LC) calculated was 185.2 ± 1.24 μg/mL for the ethyl acetate fraction (EAF) and 296.0 ± 1.27 μM for RA. The EAF showed free radical inhibition ranging from 23.09% to 63.44% at concentrations of 10-250 μg/mL. The RA presented a concentration-dependent response ranging from 18.24% to 47.63% at 10-250 μM. Furthermore, the RA reduced LPS induction of TNF-α and IL-1β levels, with the greatest effect observed 6 h after LPS administration. Thus, the data suggested an anti-inflammatory effect of RA isolated from B. brasiliense and reinforced the utility of the new model of neuroinflammation to test the possible neuroprotective effects of novel drugs or compounds.
神经炎症与神经退行性疾病的发展有关，有证据表明，高水平的促炎细胞因子会促进神经元功能障碍和死亡。因此，有必要研究新的化合物，通过减轻中枢神经系统（CNS）的炎症反应，作为神经退行性疾病的辅助治疗方法。本研究旨在利用脂多糖（LPS）诱导的神经炎症模型，评估从 Blechnum brasiliense 中分离得到的迷迭香酸（RA）对成年斑马鱼的炎症反应的调节作用。首先，我们研究了 Blechnum brasiliense 提取物（乙酸乙酯部分-EAF）和分离得到的 RA 在斑马鱼胚胎中的毒性和抗氧化特性。接下来，我们通过腹腔内（i.p.）注射 LPS 建立了神经炎症诱导模型，观察 RA 对促炎细胞因子的调节作用。计算得出的乙酸乙酯部分（EAF）的半数致死浓度（LC）为 185.2±1.24μg/mL，RA 的半数致死浓度（LC）为 296.0±1.27μM。EAF 在 10-250μg/mL 浓度范围内的自由基抑制率为 23.09%-63.44%。RA 在 10-250μM 浓度范围内呈浓度依赖性反应，范围为 18.24%-47.63%。此外，RA 降低了 LPS 诱导的 TNF-α和 IL-1β水平，在 LPS 给药后 6 小时观察到最大效果。因此，数据表明，从 Blechnum brasiliense 中分离得到的 RA 具有抗炎作用，并加强了新的神经炎症模型的实用性，以测试新型药物或化合物的潜在神经保护作用。
