Effects of Artemisinin on Escherichia coli–Induced Mastitis in Bovine Mammary Epithelial Cells and Mice

SIMPLE SUMMARY: Bovine mastitis is a persistent and inflammatory reaction of the udder tissue that is usually caused by microbial infection, which can result in substantial losses due to reduced milk yield. Escherichia coli is considered a causative environmental pathogen and has been reported as a common cause of bovine mastitis worldwide. Because of its pathogenicity, Escherichia coli is always an important problem to the dairy industry worldwide and also poses a threat to food safety and public health, and with the widespread use of antibiotics, the resistance of Escherichia coli is increasing. Despite considerable research on bovine mastitis, the disease still remains one of the most prevalent and costly diseases of the dairy industry. The need to control mastitis is driven by multiple considerations, including milk quality, reductions in antimicrobial use, and animal welfare. Artemisinin is an antimalarial drug that was developed from a Chinese traditional herb, Qinghao. In recent years, other effects of artemisinin (including antitumor, anti-inflammatory, antifungal, etc.) have been increasingly discovered and applied. In this study, we demonstrated that artemisinin possesses a protective effect toward Escherichia coli–induced mastitis, thus providing a practical approach for the clinical control of mastitis. ABSTRACT: Bovine mastitis is an important disease affecting dairy farming, and it causes large economic losses to the dairy industry. Escherichia coli (E. coli) is considered to be a causative environmental pathogen and frequently enters into mammary glands, causing inflammation. Artemisinin is a highly effective malaria remedy and is not easy to develop drug resistance to. In recent years, other effects of artemisinin (including antitumor, anti-inflammatory, antifungal, etc.) have been increasingly discovered and applied. The current study aimed to investigate whether artemisinin could attenuate E. coli–induced inflammation. Through the E. coli mastitis model in MAC-T cells and mice, the protective effects of artemisinin were analyzed by CCK-8 (Cell Counting Kit-8), Western blot, and RT-qPCR. The results showed that artemisinin reversed the decrease of cell viability and upregulated TLR4 (toll-like receptor 4)/NF-κB (nuclear factor κB) and MAPK (mitogen activated protein kinase)/p38 signaling pathways, as well as restrained the expression of TNF-α, IL-6, and IL-1β mRNA caused by E. coli. Meanwhile, artemisinin also alleviated mammary tissue damage, reduced inflammatory cells’ infiltration, and decreased the levels of inflammatory factors in a mice mastitis model. This study demonstrated that artemisinin alleviated the inflammatory response of mouse mastitis and MAC-T cells induced by E. coli, thus providing a practical approach for the clinical control of mastitis.