Nisin Self-assembles to Interfere with Cellular Endocytosis for Ribosome-Mediated Anti-inflammatory Efficiency

Nisin, derived from <i>Streptococcus lactis</i>, is the only approved bacteriocin for food preservation. With wide application in multitudinous food, progressively increasing studies have focused on its anti-inflammatory activity, while its structure-effect relationship and molecular mechanism remain unclear. In this study, the anti-inflammatory efficiency and structural differences of two typical types of nisin, A and Z, were first compared based on a mouse model. The self-assembly behavior of nisin was uncovered, and the characteristics of the self-assembled nanoscale nisin were explored. Based on the transcriptomic analysis, the anti-inflammatory mechanisms of the ribosomal pathway activation of both nisin A and nisin Z were further analyzed, and the upregulation of <i>atp7b</i> and <i>entpd4</i> triggered by A and Z, respectively, and the consequent adenosine production levels elucidated the therapeutic differences. This study deepens the understanding of the structural and molecular mechanisms underlying the anti-inflammatory activity of nisin and provides an innovative horizon for the future application of nisin.