biostudies-literatureUnknown14(1)Takashima MMastitis is an inflammatory disease affecting mammary tissues caused by bacterial infection that negatively affects milk quality and quantity. S-Allylmercaptocysteine (SAMC), a sulfur compound in aged garlic extract (AGE), suppresses lipopolysaccharide (LPS)-induced inflammation in mouse models and cell cultures. However, the mechanisms underlying this anti-inflammatory effect remain unclear. In this study, we demonstrated that oral administration of AGE suppressed the LPS-induced immune response in a mastitis mouse model and that SAMC inhibited LPS-induced interleukin-6 production and nuclear factor κB p65 subunit activation in HC11 mammary epithelial cells. Global phosphoproteomic analysis revealed that SAMC treatment downregulated 910 of the 1,304 phosphorylation sites upregulated by LPScientific reports29627https://www.ebi.ac.uk/biostudies/studies/S-EPMC11604973biostudies-literatureS-allylmercaptocysteine inhibits TLR4-mediated inflammation through enhanced formation of inhibitory MyD88 splice variant in mammary epithelial cells.PMC11604973Takashima MTerai HSuzuki JIKurita MZhao FQfalseS-allylmercaptocysteine inhibits TLR4-mediated inflammation through enhanced formation of inhibitory MyD88 splice variant in mammary epithelial cells.Mastitis is an inflammatory disease affecting mammary tissues caused by bacterial infection that negatively affects milk quality and quantity. S-Allylmercaptocysteine (SAMC), a sulfur compound in aged garlic extract (AGE), suppresses lipopolysaccharide (LPS)-induced inflammation in mouse models and cell cultures. However, the mechanisms underlying this anti-inflammatory effect remain unclear. In this study, we demonstrated that oral administration of AGE suppressed the LPS-induced immune response in a mastitis mouse model and that SAMC inhibited LPS-induced interleukin-6 production and nuclear factor κB p65 subunit activation in HC11 mammary epithelial cells. Global phosphoproteomic analysis revealed that SAMC treatment downregulated 910 of the 1,304 phosphorylation sites upregulated by LP2024-01-01T00:00:00Z2024 Nov2025-04-18T16:52:16.977Z2025-04-07T04:19:50.026ZS-EPMC116049733960952510.1038/s41598-024-81304-2