Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, Hubei, PR China.
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, Hubei, PR China.
Int Immunopharmacol. 2018 Nov;64:140-150. doi: 10.1016/j.intimp.2018.08.023. Epub 2018 Aug 31.
Barbaloin is the major anthraquinone compound that is isolated from the leaf exudates of Aloe vera and is often used as a bittering agent in alcoholic beverages. Here, we investigated the potential protective role of barbaloin in a mouse model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) and clarified the underlying mechanism in vitro. Histological analysis showed that barbaloin exhibited a certain protective effect on LPS-induced ALI. To further elucidate the mechanisms underlying the actions of barbaloin, LPS-stimulated macrophages were used in this study. The results showed that barbaloin decreased the phosphorylation levels of IκBα and NF-κB p65, leading to a reduction in the expression of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6). Furthermore, barbaloin also reduced the levels of intracellular reactive oxygen species (ROS) similarly to the antioxidant N‑acetyl‑l‑cysteine (NAC), which alone repressed the LPS-induced phosphorylation of phosphoinositide 3-kinase (PI3K) and AKT. Additionally, a pharmacological inhibitor of PI3K/AKT, LY294002, also restrained the phosphorylation levels of IκBα and NF-κB p65 and thereby decreased the expression of pro-inflammatory cytokines. Together, these results show that barbaloin possesses a protective effect on LPS-induced ALI via suppressing the release of pro-inflammatory cytokines through the ROS-mediated PI3K/AKT/NF-κB pathway.
芦荟大黄素是从库拉索芦荟叶渗出液中分离得到的主要蒽醌类化合物，常被用作酒精饮料的苦味剂。在这里，我们研究了芦荟大黄素在脂多糖（LPS）诱导的急性肺损伤（ALI）小鼠模型中的潜在保护作用，并在体外阐明了其潜在机制。组织学分析表明，芦荟大黄素对 LPS 诱导的 ALI 具有一定的保护作用。为了进一步阐明芦荟大黄素作用的机制，本研究使用 LPS 刺激的巨噬细胞。结果表明，芦荟大黄素降低了 IκBα 和 NF-κB p65 的磷酸化水平，导致促炎细胞因子（TNF-α、IL-1β 和 IL-6）的表达减少。此外，芦荟大黄素还能像抗氧化剂 N-乙酰-L-半胱氨酸（NAC）一样降低细胞内活性氧（ROS）的水平，NAC 单独抑制 LPS 诱导的磷酸肌醇 3-激酶（PI3K）和 AKT 的磷酸化。此外，PI3K/AKT 的药理学抑制剂 LY294002 也抑制了 IκBα 和 NF-κB p65 的磷酸化水平，从而减少了促炎细胞因子的表达。综上所述，这些结果表明，芦荟大黄素通过 ROS 介导的 PI3K/AKT/NF-κB 途径抑制促炎细胞因子的释放，对 LPS 诱导的 ALI 具有保护作用。
