Atractylodin inhibits ferroptosis in sepsis‑induced acute gastrointestinal injury via SIRT3/PRDX3

Gastrointestinal injury (GI) is a significant concern in various medical contexts, particularly in patients undergoing antiplatelet therapy, experiencing trauma, or dealing with the effects of medications. The present study investigated the effect of atractylodin, a bioactive compound derived from <i>Atractylodes lancea</i> (Thunb.) DC., traditionally used in medicinal applications. A sepsis animal model was established through cecal ligation and perforation. Mice were treated with atractylodin, with or without silencing of NAD‑dependent protein deacetylase sirtuin‑3 (SIRT3), via transfection with adeno‑associated virus (AAV) vectors. Atractylodin markedly improved mitochondrial function <i>in vivo</i>, as evidenced by increased mitochondrial‑related proteins via western blot analysis (TOM20) and increased mitochondrial membrane potential, as observed via JC‑1 staining. In addition, atractylodin treatment inhibited apoptosis. Together, these changes regulated mitochondrial dysfunction. Moreover, atractylodin improved the prognosis of sepsis‑induced ferroptosis in the stomach and colon tissues. Atractylodin markedly activated SIRT3 while suppressing the expression of ac‑peroxiredoxin‑3 (PRDX3). Notably, the knockdown of SIRT3 diminishes the inhibitory effect of atractylodin on ferroptosis, when AAV‑short hairpinSIRT3 was injected into the stomach and colon tissues of C57 BL/6 mice. Further, atractylodin may have attenuated GI development by preventing mitochondrial dysfunction through the SIRT3/PRDX3 pathway. Hence, protection against mitochondrial dysfunction using atractylodin may be a promising therapeutic strategy against sepsis‑induced acute GI.