Unveiling the anti-inflammatory effect of <i>Perilla frutescens</i> essential oil by using multi-omics analysis in zebrafish model

Perilla frutescens essential oil (PFO) is a mixture of volatile compounds extracted from the aboveground part of Perilla frutescens (L.) Britt. Besides its pleasant aroma, PFO exhibits many biological activities, which have significant promise for the creation of functional foods. The present study aimed to reveal the anti-inflammatory effect of PFO in zebrafish tail fin amputation model by observing neutrophil migration. Our results showed that perilla ketone (42.41%) is the main component of PFO, and 3.0 μg/mL of PFO significantly inhibited neutrophils migration to the amputation site. In addition, PFO had the noticeably regulatory effect on the expression of tumor necrosis factor α, interleukin 6, and interleukin 1β. Multi-omics analysis identified two crucial genes (peptide YYa [pyya] and glula) and 20 significant metabolites affected by PFO, revealing that PFO intervenes in inflammatory response by regulating arginine biosynthesis, alanine, aspartate, and glutamate metabolism, glyoxylate and dicarboxylate metabolism, and neuroactive ligand–receptor interaction. Subsequent study showed that pyya and glula sequentially connected these metabolic pathways, and PFO could control the expression of these two crucial genes (P < 0.0001). These results serve as a significant reference for PFO’s worth in development and sensible utilization as a safe, healthy, and natural functional food in the future.