alloin and Acute-Lung-Injury

The purpose of this study was to explore the protective effects and potential mechanisms of aloin on lipopolysaccharide (LPS)-induced acute lung injury (ALI).. Mice were pretreatment with aloin 1 h before LPS administration. The number of inflammatory cells and the levels of TNF-α and IL-1β was detected. The lung histopathological changes, wet/dry ratio, MPO activity, GSH, MDA, SOD, and the expression of NF-κB and NLRP3 inflammasome were measured.. The results showed that aloin significantly inhibited the number of total cells, neutrophils, and macrophages, as well as the levels of TNF-α and IL-1β in BALF induced by LPS. In addition, pretreatment with aloin also inhibited LPS-induced lung histopathological injuries, lung wet/dry ratio, MPO activity, and MDA content. The levels of GSH and SOD were decreased by LPS and treatment of aloin could increase the levels of GSH and SOD. To study the protective mechanisms of alion on LPS-induced ALI, the expression of SIRT1, NF-κB and NLRP3 inflammasome were tested. We found that aloin significantly inhibited the activation of NF-κB and NLRP3 inflammasome in ALI induced by LPS. Meanwhile, aloin was found to increase the expression of SIRT1 and inhibition of SIRT1 by EX-527 reversed the protective effects of aloin.. These results suggest that aloin exerts its protective effects on LPS-induced ALI by activation SIRT1, which subsequently results in the suppression of NF-κB and NLRP3 inflammasome.

Topics: Acute Lung Injury; Aloe; Animals; Dose-Response Relationship, Drug; Emodin; Female; Lipopolysaccharides; Macrophages; Mice; Mice, Inbred C57BL; Neutrophils; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Sirtuin 1

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.

Topics: Acute Lung Injury; Animals; Anthracenes; Anti-Inflammatory Agents; Lipopolysaccharides; Mice; Mice, Inbred BALB C; NF-kappa B; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Signal Transduction; Toll-Like Receptor 4