Isoglycyrrhizin protects mouse lungs against acute respiratory distress syndrome via regulation of AMPK/Nrf2/ARE pathway

Purpose: To study the effect of isoglycyrrhizin on LPS-mediated acute respiratory distress syndrome (ARDS) in a mouse model, as well as the associated mechanism of action.Methods: Ninety (90) wild-type C57BL/6 male mice were randomly assigned to 3 groups, viz, control, ARDS and isoglycyrrhizin groups. Pathological lesions in mice lungs were determined using H&E staining. The mRNA and protein expressions of inducible nitric oxide synthase (iNOS), heme oxygenase (HO-1), cyclooxygenase-2 (COX-2), AMP- dependent protein kinase (AMPK), serine/threonine proteinkinase (Akt), glycogen synthase kinase 3 (GSK3), nucleotide-binding domain-like receptor protein 3 (NLRP3), and Nrf2 were assayed using quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunoblotting, respectively.Results: The levels of mRNA and protein expressions of INO) and COX-2 were significantly upregulated in ARDS, when compared to control, but were markedly down-regulated by isoglycyrrhizin (p < 0.05). Similarly, exposure of ARDS mice to isoglycyrrhizin led to upregulations of mRNA and proteinlevels of Nrf2, NQO1, HO-1, GCLM, GCLC, p-GSK3, GSK3, p-AMPK, AMPK, p-Akt and AKT (p < 0.05). Moreover, isoglycyrrhizin significantly downregulated p-IκB and Nucl-p65 with respect to protein and mRNA levels, but upregulated IκBα expression. Histopathological examination revealed that pretreatment of ARDS mice with isoglycyrrhizin significantly reduced the number of infiltrating inflammatory cells, edema and ARDS score (p < 0.05).Conclusion: Isoglycyrrhizin protects mouse lungs against ARDS via regulation of AMPK/Nrf2/ARE pathway. Thus, this compound has potential for use in the treatment of ARDS.