Investigation of c-Fos/c-Jun Signaling Pathways in Periostracum Cicadae’s Inhibition of EMT in Gastric Tissue

Background/Objectives: Periostracum Cicadae (PC) is commonly used to treat chronic atrophic gastritis (CAG), but its underlying mechanisms are unclear. We investigated the therapeutic effects, active ingredients and molecular mechanisms of PC on CAG. Methods: We analyzed the components in the serum extract of PC by UHPLC-Q-Orbitrap-MS/MS. Then, we used rat and cell models to assess the impact of PC on CAG and employed network pharmacology and bioinformatics to predict key targets and active ingredients. Finally, we confirmed hub targets through experiments and molecular docking. Results: A total of 22 components were identified in the PC extract-containing serum using UHPLC-Q-Orbitrap MS/MS. Network pharmacology combined with molecular docking revealed that the protective effect was primarily mediated by three compounds: (Z)-akuammidine, chicoric acid, and columbianadin. And we revealed that c-Fos/c-Jun signaling pathways were crucial in therapy. PC extract-containing serum inhibited the vitality, migration, invasion, and multiplication of MC cells (model cells for CAG), induced apoptosis, and caused G0/G1 phase cell cycle arrest. The expression level of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β) and gastrin 17 (G17) in the serum of CAG rats increased, while the expression level of pepsinogen I (PG I) and pepsinogen II (PG II) decreased. After 12 weeks of PC administration, these conditions were significantly improved. PC not only reduced the levels of antigen KI-67 (Ki67) and tumor protein p53 (P53) but also enhanced SRY-box Transcription Factor (SOX2). Simultaneously, PC down-regulated the expression of N-cadherin and Vimentin while up-regulating that of E-cadherin. Conclusions: PC inhibited epithelial–mesenchymal transition (EMT) via the c-Fos/c-Jun signaling pathway, thereby providing therapeutic benefits for CAG. Our study elucidates the mechanisms and material basis of PC in treating CAG, providing experimental evidence to support its clinical application.