Eupatilin Attenuates Mastitis in Dairy Cows by Activating the NRF2 Pathway

Antibiotic treatment of mastitis in dairy cows can cause antibiotic residues and antimicrobial resistance, highlighting the urgent need for eco-friendly and sustainable alternatives. Here, we show that dairy cows with mastitis have severe inflammation, apoptosis, and oxidative stress in mammary tissue. Eupatilin (EU), a natural compound derived from Artemisia argyi, alleviated LPS-induced pathological damage in bovine mammary epithelial cells (BMECs) by enhancing the transcriptional activity of NRF2. Knockdown of NRF2 abolished the protective effects of EU against LPS-induced inflammation, apoptosis, and oxidative stress in BMECs, whereas overexpression of NRF2 did not further enhance these effects. Importantly, the protective effect of EU against LPS-induced mastitis in mice was fully reversed by pharmacological inhibition of NRF2. This work not only identifies NRF2 as a potential therapeutic target for combating mastitis but also identifies EU as a promising therapeutic agent and an effective non-antibiotic option for the prophylaxis and therapy of mastitis.