Aloin suppresses lipopolysaccharide-induced acute lung injury by inhibiting NLRP3/NF-κB via activation of SIRT1 in mice.
Immunopharmacol Immunotoxicol. 2020 Aug ;42(4):306-313. Epub 2020 May 18. PMID: 32419528
OBJECTIVE: The purpose of this study was to explore the protective effects and potential mechanisms of aloin on lipopolysaccharide (LPS)-induced acute lung injury (ALI).
METHODS: 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.
RESULTS: 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 expressionof SIRT1 and inhibition of SIRT1 by EX-527 reversed the protective effects of aloin.
CONCLUSIONS: 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.