Self-Assembled Particles from Raw and Bran-Fried Atractylodes lancea Exert Spleen-Strengthening Effects via TFF1/NF-κB Pathway and Gut Microbiota Remodeling

Background:Atractylodes lancea (AR) is a commonly used spleen-strengthening herb, but its clinical application is limited by the poor bioavailability of its active components. We found that AR spontaneously forms self-assembled particles during decoction, and bran-frying may further optimize this process to enhance its therapeutic efficacy against spleen deficiency syndrome (SDS). Objective: This study aimed to determine whether bran-frying enhances the efficacy of AR by forming more stable self-assembled particles with improved delivery performance, and to clarify the dual mechanisms by which these particles alleviate SDS through regulation of the TFF1/NF-κB pathway and modulation of the gut microbiota. Results: Compared with raw AR self-assembled particles (ARSs), bran-fried AR self-assembled particles (ARFs) exhibited higher atractylodin loading (1.17% vs. 0.96%), smaller particle sizes, and greater absolute zeta potential. ARFs also showed significantly higher cumulative release of all four active components, with atractylodin release approximately six-fold that of ARSs. Both particles significantly reduced intestinal inflammatory cytokine levels, restored barrier-associated molecular markers, and downregulated TFF1/NF-κB p65 protein expression. Via 16S rRNA sequencing, it was revealed that the self-assembled particles reversed SDS-induced gut dysbiosis, characterized by increased abundance of beneficial Dubosiella and decreased abundance of pathogenic Escherichia-Shigella. Fecal microbiota transplantation and antibiotic depletion experiments further verified the regulatory role of self-assembled particles on the gut microbiota. Conclusions: Both raw and bran-fried AR can form self-assembled particles, and bran-frying enhances their biological characteristics. The self-assembled particles exert spleen-strengthening effects through dual mechanisms involving regulation of the TFF1/NF-κB pathway and modulation of the gut microbiota.