Geniposide Possesses the Protective Effect on Myocardial Injury by Inhibiting Oxidative Stress and Ferroptosis via Activation of the Grsf1/GPx4 Axis

• DOI: 10.3389/fphar.2022.879870
• Publication Date: 2022-05-05T04:59:53Z
• Authors: Yuehong Shen; Xindong Wang; Xinyu Shen; Yue Wang; Shulin Wang; Yunyun Zhang; Xiaoming Yao; Yijiao Xu; Ming Sang; Jiamin Pan; Yu Qin; Qian Zhou; Jianping Shen
• Keywords: GPX4

Reactive oxygen species (ROS) produced in the ischemic myocardium can induce cardiomyocyte injury and death, resulting cardiac remodeling. Ferroptosis, known as a newly type of cell death caused by iron-dependent oxidative stress, which is an essential mechanism cardiomyocytes. However, it unclear whether stress products further ferroptosis aggravate injury. Geniposide (GEN), major active component Gardenia jasminoides J. Ellis , possesses natural antioxidant activity cardioprotective effect. Herein, we evaluated role myocardial protective effect GEN on ferroptosis. We first detected iron overload, massive ROS, lipid peroxidation ferric ammonium citrate (FAC)-treated cardiomyocytes, were typical characteristics The overload-induced aggravated injury, significantly alleviated treatment. Similar phenotypic changes consistently discovered hydrogen peroxide (H 2 O )-induced cells, reversed treatment well. Interestingly, RNA-binding protein Grsf1, directly upregulated Gpx4 at translational level, was activated following specific knockdown Grsf1 increased their sensitivity to weakened H -treated Moreover, reduced overload infarction (MI) rats, thereby fighting against Collectively, our study revealed pathogenesis associated with ischemia, indicated anti-ferroptosis effects preventing activating Grsf1/GPx4 axis, serving potential therapeutic target.