Formulation and biological evaluation of a Perilla frutescens seed oil nanoemulsion: A novel therapeutic agent for alleviating gut-liver axis inflammation

Background The gut-liver axis is integral to the pathophysiology of chronic liver inflammation and related metabolic inflammatory disease. Although Perilla frutescens seed oil (PFSO) possesses anti-inflammatory properties, its clinical application is limited by its poor stability and bioavailability. This study aimed to develop a PFSO-loaded nanoemulsion (PFSO-NE) to enhance its therapeutic efficacy. Methods The PFSO-NE was optimized using pseudoternary phase diagrams, and its physicochemical properties were thoroughly characterized. The therapeutic effects of PFSO-NE were assessed in lipopolysaccharide (LPS) mice using a combination of biochemical assays, histological examinations, quantitative PCR, 16S rDNA sequencing, and short-chain fatty acid (SCFA) analyses. Results PFSO-NE demonstrated a small particle size (32.77 nm), high encapsulation efficiency (93.02%), and enhanced stability. This led to a significant reduction in the levels of inflammatory cytokines, specifically TNF-α and IL-6, increased IL-10 levels, mitigated tissue damage, and modulated the gut microbiota by enriching beneficial bacteria, such as Lachnospiraceae, and elevating acetate concentrations. Conclusions PFSO-NE effectively attenuates inflammation in the gut-liver axis by enhancing bioavailability, modulating immune responses, and remodeling the gut microbiota, thereby providing preclinical evidence for PFSO-NE as a promising natural nanoformulation for the potential treatment of inflammatory diseases.