ZDHHC12-dependent Nrf2 palmitoylation mediates the anti-ferroptotic and anti-inflammatory effects of artemisinin in mastitis.

Authors

Zeqiu Fan, Yang Luo, Zhenzhao Zhang, Feng Cheng, Kangle Yi, Wenjun Liu

Published in

Communications biology. Jul 16, 2026. Epub Jul 16, 2026.

Abstract

Artemisinin (ART) is known to alleviate inflammation in mastitis, but its effect on ferroptosis in mammary epithelial cells and the associated regulatory mechanisms has not been fully clarified. Here, we demonstrate that ART markedly attenuates inflammatory injury and ferroptosis in Staphylococcus aureus-induced mastitis models both in vivo and in vitro. ART treatment reduces iron accumulation and lipid peroxidation while restoring antioxidant capacity, accompanied by improved mitochondrial integrity. Mechanistically, ART upregulates the palmitoyltransferase ZDHHC12, which promotes palmitoylation of nuclear factor erythroid 2-related factor 2 (Nrf2) and facilitates its nuclear translocation. Activation of Nrf2 subsequently enhances heme oxygenase-1 (HO-1) signaling, leading to suppression of inflammation and ferroptosis. Collectively, these findings reveal that ART exerts protective effects against mastitis by activating the ZDHHC12/Nrf2/HO‑1 axis, highlighting ART as a potential therapeutic agent for mastitis through coordinated inhibition of inflammation and ferroptosis.

PMID:
42463850
Bibliographic data and abstract were imported from PubMed on 17 Jul 2026.

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