Work

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

Year: 2026

Type: article

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.

Source: Communications Biology

DOI: 10.1038/s42003-026-10677-z

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

Institutions: Guangxi University, Hunan Academy of Agricultural Sciences, China Agricultural University, Shenzhen Medical Academy of Research and Translation

Language: English

Topic: Genomics, phytochemicals, and oxidative stress

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,190