Hordenine Alleviates\nLipopolysaccharide-Induced Mastitis\nby Suppressing Inflammation and Oxidative Stress, Modulating Intestinal\nMicrobiota, and Preserving the Blood–Milk Barrier

Mastitis\nis a common mammalian disease occurring in the\nmammary\ntissue and poses a major threat to agriculture and the dairy industry.\nHordenine (HOR), a phenylethylamine alkaloid naturally extracted from\nmalt, has various pharmacological effects, but its role in mastitis\nis unknown. The aim of this study was to investigate the role of HOR\nand its underlying mechanism in a lipopolysaccharide (LPS)-induced\ninflammatory response model of mouse mammary epithelial cells (EpH4-Ev)\nand mouse mastitis model. The experimental results showed that HOR\nattenuated LPS-induced mammary tissue damage (from 3.75 ± 0.25\nto 1.75 ± 0.25) and restored the integrity of the blood–milk\nbarrier. Further mechanistic studies revealed that HOR inhibited LPS-induced\noveractivation of the TLR4-MAPK/NF-κB signaling pathway and\nactivated the AMPK/Nrf2/HO-1 signaling pathway. Additionally, HOR\naltered the composition of the intestinal microbiota in mice, ultimately\nreducing the extent of inflammatory injury (from 3.33 ± 0.33\nto 0.67 ± 0.33) and upregulating the expression of tight junction\nproteins (ZO-1, occludin, and claudin-3). The findings of this study\nprovide a theoretical basis in the rational use of HOR for the prevention\nand treatment of mastitis and the maintenance of mammalian mammary\ngland health.