Old targets, new strategy: Apigenin-7-O- β-d-(-6″-p-coumaroyl)-glucopyranoside prevents endothelial ferroptosis and alleviates intestinal ischemia-reperfusion injury through HO-1 and MAO-B inhibition
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.PMID:35398494 | DOI:10.1016/j.freeradbiomed.2022.03.033
Source: Free Radical Biology and Medicine - Category: Biology Authors: Ying-Da Feng Wen Ye Wen Tian Jing-Ru Meng Meng Zhang Yang Sun Hui-Nan Zhang Shou-Jia Wang Ke-Han Wu Chen-Xu Liu Shao-Yuan Liu Wei Cao Xiao-Qiang Li Source Type: research