Albanin G: A multi-target aminoacyl-tRNA synthetase inhibitor from the root bark of Morus alba and its anti-mastitis activity

Mastitis in cattle is a disease primarily caused by bacteria such as Streptococcus agalactiae and is considered a major source of contamination in the dairy industry. Therefore, there is an urgent need to explore new treatment methods, particularly through the use of natural products. In this study, seven flavonoid compounds were isolated from the bark of the Morus alba , and their antibacterial activity was evaluated against major pathogens associated with bovine mastitis, including Escherichia coli , Staphylococcus aureus , Streptococcus dysgalactiae , and Streptococcus agalactia e by the standard broth dilution method. Investigation reveals that Albanin G ( 7 ) possessed superior antibacterial activity against S. agalactiae , with a MIC value of 1.56 μg/mL, outperforming the control agent norfloxacin. Proteomics analysis, parallel reaction monitoring (PRM), and transcriptomic analysis showed that Albanin G ( 7 ) inhibited the aminoacyl-tRNA biosynthesis pathway by suppressing the activity of six aminoacyl-tRNA synthetases (aaRSs). Furthermore, in vitro phenotypic assays verified that Albanin G ( 7 ) suppressed protein synthesis, impaired biofilm formation and virulence factor production, and compromised cell membrane integrity and increased permeability. The mastitis mouse model revealed that Albanin G ( 7 ) effectively treated mastitis caused by S. agalactiae by significantly reducing oxidative stress and downregulating the pro-inflammatory cytokines TNF- α , IL-1 β , IL-6, and IL-8, and demonstrated good safety. Therefore, Albanin G ( 7 ) has the potential to serve as a candidate compound for the development of treatments for bovine mastitis, helping to reduce contamination in the dairy industry and contributing to the production of high-quality, safe dairy products.