With the increasing morbidity and mortality, intestinal
ischemia/reperfusion injury (IIRI) has attracted more and more attention, but there is no efficient
therapeutics at present. Apigenin-7-O-β-D-(-6″-p-coumaroyl)-glucopyranoside (APG) is a new
flavonoid glycoside isolated from Clematis tangutica that has strong
antioxidant abilities in previous studies. However, the pharmacodynamic function and mechanism of APG on IIRI remain unknown. This study aimed to investigate the effects of APG on IIRI both in vivo and in vitro and identify the potential molecular mechanism. We found that APG could significantly improve intestinal
edema and increase Chiu's score. MST analysis suggested that APG could specifically bind to
heme oxygenase 1 (HO-1) and
monoamine oxidase b (
MAO-B). Simultaneously, APG could attenuate ROS generation and Fe2+ accumulation, maintain mitochondria function thus inhibit ferroptosis with a dose-dependent manner. Moreover, we used
siRNA silencing technology to confirm that knocking down both HO-1 and
MAO-B had a positive effect on intestine. In addition, we found the HO-1 and
MAO-B inhibitors also could reduce endothelial cell loss and protect vascular endothelial after reperfusion. We demonstrate that APG plays a protective role on decreasing activation of HO-1 and
MAO-B, attenuating IIRI-induced ROS generation and Fe2+ accumulation, maintaining mitochondria function thus inhibiting ferroptosis.