Syringin alleviates ROS-induced acute lung injury by activating SIRT1/STAT6 signaling pathway to inhibit ferroptosis

Introduction: Acute lung injury (ALI) is the critical respiratory condition. Syringin with anti-inflammatory and anti-oxidant properties can exhibit the lung protective effects. SIRT1 and STAT6 can exert protective roles against lung injury by inhibiting ferroptosis.

Methods: In the current study, A549 lung epithelial cells were treated with 200 μM H₂O₂ for 2 h to establish an in vitro ALI model. Then, H₂O₂-stimulated A549 cells were treated with syringin to identify the biological role of syringin in ROS-induced ALI. Moreover, H₂O₂-stimulated A549 cells were further treated with SIRT1 inhibitor EX527 or ferroptosis activator erastin to elucidate whether syringin could exert protective effects against ROS-induced ALI depending on SIRT1/STAT6 signaling-mediated ferroptosis inhibition.

Results: It was verified that syringin treatment improved the impaired viability and mitigated inflammatory response and oxidative stress of H₂O₂-stimulated A549 lung epithelial cells by activating SIRT1/STAT6 signaling pathway. Syringin treatment inhibited the ferroptosis of H₂O₂-stimulated A549 lung epithelial cells by activating SIRT1/STAT6 signaling pathway. Treatment with SIRT1 inhibitor EX527 or ferroptosis activator erastin both reversed the alleviating effect of syringin on H₂O₂-induced A549 lung epithelial cell injury.

Conclusion: To sum up, syringin treatment alleviates H₂O₂-induced lung epithelial cell injury by activating SIRT1/STAT6 signaling pathway to inhibit ferroptosis.