Abstract
INTRODUCTION: Postoperative ileus (POI) is a common complication following abdominal surgery, with limited preventive and therapeutic strategies. Dajianzhong Decoction (DJZD), a classic formula in traditional Chinese medicine, has demonstrated clinical potential in alleviating POI, yet its underlying composition and molecular mechanisms remain to be systematically elucidated. METHODS: HPLC fingerprinting was performed on 30 batches of DJZD, and spectrum-effect correlation analysis was conducted by correlating fingerprint data with 5-HT secretion levels in RIN-14B cells. A rat POI model was established to compare the effects of preoperative preventive and postoperative therapeutic administration of DJZD on gastrointestinal motility. Serum untargeted metabolomics was employed to identify differentially expressed metabolites and analyze relevant metabolic pathways. RESULTS: Eleven key metabolite from DJZD were screened and confirmed, namely, ginsenoside Rg(1), ginsenoside Re, γ-Sanshool, 10-gingerol, ginsenoside Rb1, ginsenoside Rc, ginsenoside Rb3, ginsenoside Rb2, ginsenoside Rd, hydroxy-α-sanshool and hydroxy-β-sanshool. Among these conmponents, ginsenoside Rc and ginsenoside Rd were identified as the primary metabolites associated with DJZD's regulation of 5-HT secretion. Both preoperative and postoperative administration of DJZD significantly improved gastrointestinal motility in POI rats, with preoperative intervention showing more pronounced effects. Metabolomic analysis revealed that DJZD modulated several key pathways, including tryptophan metabolism, steroid hormone biosynthesis, and glycerophospholipid metabolism. CONCLUSION: DJZD alleviates POI through multi-component, multi-pathway mechanisms involving the modulation of intestinal 5-HT signaling and systemic metabolic reprogramming. This study provides a pharmacological basis for the clinical use of DJZD in POI and exemplifies the holistic regulatory characteristics of traditional Chinese medicine.