EGCG-NPs inhibition HO-1-mediated reprogram iron metabolism against ferroptosis after subarachnoid hemorrhage

• Published in: Redox biology Vol. 70; p. 103075
• Main Authors: Huang, Liyong, Wang, Xue, Zheng, Yanning, Lang, Dongcen, Wang, Jian, Yan, Shuaiguo, Chen, Ying
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2024; Elsevier
• Subjects: Catechin - analogs & derivatives; Catechin - pharmacology; Catechin - therapeutic use; EGCG; Ferroptosis; Heme oxygenase-1; Humans; Iron; Iron metabolism; Research Paper; Subarachnoid hemorrhage; Subarachnoid Hemorrhage - drug therapy; Ferroptosis; Iron metabolism; Subarachnoid hemorrhage; EGCG; Heme oxygenase-1
• ISSN: 2213-2317; 2213-2317
• DOI: 10.1016/j.redox.2024.103075

Subarachnoid hemorrhage (SAH), a devastating disease with a high mortality rate and poor outcomes, tightly associated with the dysregulation of iron metabolism and ferroptosis. (-)-Epigallocatechin-3-gallate (EGCG) is one of major bioactive compounds of tea catechin because of its well-known iron-chelating and antioxidative activities. However, the findings of iron-induced cell injuries after SAH remain controversial and the underlying therapeutic mechanisms of EGCG in ferroptosis is limited. Here, the ability of EGCG to inhibit iron-induced cell death following the alleviation of neurological function deficits was investigated by using in vivo SAH models. As expected, EGCG inhibited oxyhemoglobin (OxyHb)-induced the over-expression of HO-1, which mainly distributed in astrocytes and microglial cells. Subsequently, EGCG blocked ferrous iron accumulation through HO-1-mediated iron metabolic reprogramming. Therefore, oxidative stress and mitochondrial dysfunction was rescued by EGCG, which resulted in the downregulation of ferroptosis and ferritinophagy rather than apoptosis after SAH. As a result, EGCG exerted the superior therapeutic effects in the maintenance of iron homeostasis in glial cells, such as astrocytes and microglial cells, as well as in the improvement of functional outcomes after SAH. These findings highlighted that glial cells were not only the iron-rich cells in the brain but also susceptible to ferroptosis and ferritinophagy after SAH. The detrimental role of HO-1-mediated ferroptosis in glial cells can be regarded as an effective therapeutic target of EGCG in the prevention and treatment of SAH.