Wuxi School of Medicine, Jiangnan University, PR China; School of Food Science and Technology, Jiangnan University, PR China.
Department of Anesthesiology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, PR China.
Int Immunopharmacol. 2021 Jan;90:107187. doi: 10.1016/j.intimp.2020.107187. Epub 2020 Nov 25.
Sophoricoside (SOP), an isoflavone glycoside isolated from seed of Sophora japonica L., has been reported to have various pharmacological activities, including anti-cancer, anti-allergy and anti-inflammation. However, the effect of SOP on lipopolysaccharides (LPS)-acute lung injury (ALI) is completely unclear. Here, we found that SOP pretreatment significantly ameliorated LPS-induced pathological damage, tissue permeability, neutrophil infiltration and the production of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in a murine model of ALI. Besides, SOP reduced the production of pro-inflammatory mediators such as iNOS, NO and inflammatory cytokines including TNF-α, IL-1β and IL-6 in LPS-stimulated RAW264.7 cells and bone marrow derived macrophages. Interestingly, treatment with SOP exhibited no effect on the activation of NF-κB and MAPKs in macrophages but prominently accelerated the expression and nuclear translocation of Nrf2. By using ML385, a specific Nrf2 inhibitor, we found that inhibition of Nrf2 abolished the inhibitory effect of SOP on LPS-induced iNOS expression, NO production as well as pro-inflammatory cytokine generation. SOP also activated AMPK, an upstream protein of Nrf2, under LPS stimuli. Furthermore, we demonstrated that the accelerated expression of Nrf2 induced by SOP was reversed by interference with the AMPK inhibitor Compound C. Taken together, our results suggested that SOP attenuated LPS-induced ALI in AMPK/Nrf2 dependent manner and indicated that SOP might be a potential therapeutic candidate for treating ALI/ARDS.
槐糖苷（SOP）是从槐属植物种子中分离得到的一种异黄酮糖苷，具有多种药理活性，包括抗癌、抗过敏和抗炎作用。然而，SOP 对脂多糖（LPS）-急性肺损伤（ALI）的作用尚不清楚。在这里，我们发现 SOP 预处理可显著改善 LPS 诱导的小鼠 ALI 模型中的病理损伤、组织通透性、中性粒细胞浸润和促炎细胞因子（TNF-α、IL-1β 和 IL-6）的产生。此外，SOP 减少了 LPS 刺激的 RAW264.7 细胞和骨髓来源的巨噬细胞中促炎介质如 iNOS、NO 和炎症细胞因子 TNF-α、IL-1β 和 IL-6 的产生。有趣的是，SOP 对巨噬细胞中 NF-κB 和 MAPKs 的激活没有影响，但明显加速了 Nrf2 的表达和核易位。使用 ML385，一种特定的 Nrf2 抑制剂，我们发现抑制 Nrf2 消除了 SOP 对 LPS 诱导的 iNOS 表达、NO 产生以及促炎细胞因子产生的抑制作用。SOP 还在 LPS 刺激下激活了 Nrf2 的上游蛋白 AMPK。此外，我们证明 SOP 加速表达的 Nrf2 可被 AMPK 抑制剂 Compound C 干扰所逆转。总之，我们的结果表明，SOP 通过 AMPK/Nrf2 依赖性方式减轻 LPS 诱导的 ALI，并表明 SOP 可能是治疗 ALI/ARDS 的潜在治疗候选物。
