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 HO for 2 h to establish an in vitro ALI model. Then, HO-stimulated A549 cells were treated with syringin to identify the biological role of syringin in ROS-induced ALI. Moreover, HO-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 HO-stimulated A549 lung epithelial cells by activating SIRT1/STAT6 signaling pathway. Syringin treatment inhibited the ferroptosis of HO-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 HO-induced A549 lung epithelial cell injury.

CONCLUSION

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