Nisin A elevates adenosine to achieve anti-inflammatory activity.

Inflammation is a ubiquitous physiological status that exists during the occurrence, development and prognosis of numerous diseases. Clinical anti-inflammatory drugs mainly include antibiotics, antivirals, non-steroids and corticosteroids, and the treatments are often accompanied by side effects, including nausea, abdominal pain, allergy, nerve injury and organ dysfunction. Current studies have focused on continuously exploring efficient anti-inflammatory natural components with high biosafety, while nisin, a natural bioactive anti-microbial peptide produced by Lactococcus, has been reported to have anti-inflammatory activity via its superior anti-bacterial abilities. Several recent studies have focused on the potent direct anti-inflammation of nisin, whereas its effects and the corresponding mechanism still remain unclear. The cellular and Caenorhabditis elegans (C. elegans) models were constructed in this study to evaluate the anti-inflammatory effects of nisin A both in vitro and in vivo, while the inflammatory mechanism was further uncovered based on omics analysis. This study reveals the direct anti-inflammatory activity of nisin A and elucidates the regulatory actions of nisin A on adenosine, followed by alteration of the sphingolipid signaling pathway and purine metabolism, enhancing the deep understanding of nisin A with its anti-inflammatory capacity, providing new ideas for future nisin A-based anti-inflammatory strategies.