Fig. 1
The role of SLC7A11-GSH-GPX4 axis in natural products—modulated ferroptosis in respiratory diseases. The modulations of ferroptosis by natural products in respiratory diseases are orchestrated through various mechanisms, prominently via GPX4-related pathways. These pathways crucially influence lipid peroxidation, an essential process in ferroptosis. Natural products up-regulate Nrf2 gene expression, stimulating its downstream target HO-1 and enhancing SLC7A11 protein expression. Consequently, GPX4 is activated either directly or indirectly, inhibiting ferroptosis. Moreover, multiple targets are involved in regulating the SLC7A11/GPX4 axis, including the activation of system Xc− , which facilitates GSH synthesis and GPX4 activation to modulate ferroptosis. On the contrary, ACSL4 overexpression catalyzes the oxidation of PUFAs into lipid hydroperoxides. These hydroperoxides are then converted into non-toxic lipid alcohols through GPX4 activation. In the context of the immune response, Interleukin IL-17 hinders GPX4, leading to induced ferroptosis. Notations: Black Arrow (↓): Indicates promotion. Red Rough Arrow (⟂): Indicates inhibition. Green Arrow: Indicates a decrease. Red Arrow: Indicates a increase.