de Oliveira Maria Talita Pacheco, Coutinho Diego de Sá, Guterres Sílvia Stanisçuaski, Pohlmann Adriana Raffin, Silva Patrícia Machado Rodrigues E, Martins Marco Aurélio, Bernardi Andressa
Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, Brazil.
Pharmaceutical Sciences Post-Graduation Program, College of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre 90035-003, Brazil.
Pharmaceutics. 2021 May 10;13(5):683. doi: 10.3390/pharmaceutics13050683.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are inflammatory and oxidative imbalance lung conditions with no successful pharmacological therapy and a high mortality rate. Resveratrol (RSV) is a plant-derived stilbene that presents anti-inflammatory and antioxidant effects. However, its therapeutic application remains limited due to its poor bioavailability, which can be solved by the use of nanocarriers. Previously, we demonstrated that nanoencapsulated RSV (RSV-LNC) pre-treatment, performed 4 h before lipopolysaccharide (LPS) stimulation in mice, increased its anti-inflammatory properties. In this study, we evaluated the anti-inflammatory and antioxidant effects, and lung distribution of RSV-LNCs administered therapeutically (6 h post LPS exposure) in a lung injury mouse model. The results showed that RSV-LNCs posttreatment improved lung function and diminished pulmonary inflammation. Moreover, RSV-LNC treatment enhanced the antioxidant catalase level together with a decrease in the oxidative biomarker in mouse lungs, which was accompanied by an increase in pulmonary Nrf2 antioxidant expression. Finally, the presence of RSV in lung tissue was significantly detected when mice received RSV-LNCs but not when they received RSV in its free form. Together, our results confirm that RSV nanoencapsulation promotes an increase in RSV bioavailability, enhancing its therapeutic effects in an LPS-induced lung injury model.
急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）是炎症性和氧化失衡的肺部疾病，目前尚无成功的药物治疗方法，死亡率很高。白藜芦醇（RSV）是一种植物来源的芪类化合物，具有抗炎和抗氧化作用。然而，由于其生物利用度差，其治疗应用仍然有限，而使用纳米载体可以解决这一问题。此前，我们证明在小鼠脂多糖（LPS）刺激前4小时进行纳米包封的RSV（RSV-LNC）预处理，可增强其抗炎特性。在本研究中，我们评估了在肺损伤小鼠模型中治疗性给予RSV-LNCs（LPS暴露后6小时）的抗炎和抗氧化作用以及在肺中的分布。结果表明，RSV-LNCs治疗后改善了肺功能并减轻了肺部炎症。此外，RSV-LNC治疗提高了抗氧化过氧化氢酶水平，同时降低了小鼠肺中的氧化生物标志物水平，这伴随着肺中Nrf2抗氧化剂表达的增加。最后，当小鼠接受RSV-LNCs时，在肺组织中可显著检测到RSV的存在，而当它们接受游离形式的RSV时则未检测到。总之，我们的结果证实RSV纳米包封提高了RSV的生物利用度，增强了其在LPS诱导的肺损伤模型中的治疗效果。
