Mechanism of 1,25(OH)2D3 in the Treatment of Acute Lung Injury Based on UHPLC/Q-TOF MS-Based Metabolomics and Network Pharmacology

Background: Sepsis-induced acute lung injury (ALI), a high morbidity and mortality disease, still has no effective therapies. 1,25(OH) 2 D 3 is one of the indispensable nutrients in our body. The regulation mechanism of 1,25(OH) 2 D 3 in inflammation has been recognized gradually. Network pharmacology was used wildly to broaden the understanding of diseases and advance drug discovery. In this study, we used network pharmacology and metabolomics to generate the potential mechanism of 1,25(OH) 2 D 3 on acute lung injury. Methods: : We used metabolomics and network pharmacology to elucidate the therapeutic mechanism of 1,25(OH) 2 D 3 on acute lung injury. Serum samples, collected from mice with LPS-induced acute lung injury, were detected by UHPLC/Q-TOF MS to evaluate the differential metabolites from multiple metabolic pathways. Meanwhile, the H＆E staining, ELISA and QPCR were used to estimate the efficacy of 1,25(OH) 2 D 3 on acute lung injury. Results: : The results of animal experiments showed that 1,25(OH) 2 D 3 could mitigate severe pulmonary edema and inflammatory infiltration caused by LPS, and the treatment of 1,25(OH) 2 D 3 reduced the levels of inflammatory cytokines, interacted 25 related proteins and TNF signaling pathway, Toll-like receptor signaling pathway, PI3K-Akt signaling pathway. Conclusions: : The integrated methods coupled with UHPLC/Q-TOF MS and network pharmacology provided a new way to study the potential mechanism of 1,25(OH) 2 D 3 on acute lung injury, which may provide a possible solution for patients with clinical acute lung injury.