Journal Article Epublish
PubMed: 40416644 DOI: 10.1177/15593258251335814
Apigenin Inhibits Cell Ferroptosis by Activating the PI3K/Akt Pathway and Alleviates Renal Injury Caused by Hypertension.
Dose Response 23(2):15593258251335814
Authors: Haina Zhang, Yanhua Cao, Liting Jiao, Jianwei Wan
Affiliations
- Department of General Medicine, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People's Republic of China.
- Department of Pharmacy, Shanghai University of Medicine and Health Science Affiliated Zhoupu Hospital, Shanghai, People's Republic of China.
Abstract
Objectives: We aimed to explore the protective role of apigenin (API) and its underlying mechanisms in angiotensin II (Ang II)-induced hypertensive renal injury using both in vivo and in vitro models. Methods: In this study, we developed an Ang II-induced hypertensive renal injury mouse model and a recombinant IFN-γ-triggered murine podocyte clone 5 (MPC5) model in vitro. Results: API treatment reduced serum creatinine (Scr), blood urea nitrogen (BUN), and serum cystatin C (Cys-C) levels in Ang II-infused mice (all, P < .001). API reduced renal fibrosis and the expression of related molecules, including collagen I, collagen IV, fibronectin, transforming growth factor beta 1 (TGF-β1), and α-smooth muscle actin (α-SMA) (all, P < .001). The p-P13 K and p-Akt protein expression levels were improved by API treatment. API decreased the apoptotic rate, malondialdehyde (MDA) content, and mitochondrial ferrous iron, while increasing superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), which were reversed by treatment with the PI3K/Akt pathway inhibitor LY294002 (all, P < .001). In addition, API treatment reduced the expression of glutathione peroxidase 4 (GPX4) while enhancing SLC7A11 and ACSL4 expression, which was reversed by LY294002 treatment (all, P < .001). Conclusion: Our experimental data suggest that API inhibits cell ferroptosis by activating the PI3K/Akt pathway and alleviates renal injury caused by hypertension.
MeSH
Cells, Glutathione Peroxidase, Hypertension, Serum, Collagen, Ferroptosis, Apigenin, Peroxidase, Therapeutics, Glutathione, Blood Urea Nitrogen