INTRODUCTION: This study aimed to systematically compare the therapeutic efficacy of Citri Exocarpium Rubrum (CER) and Citri Grandis Exocarpium (CGE) in a rat model of Functional Dyspepsia (FD), and to explore the potential material basis and mechanisms underlying their differential effects. METHODS: A rat FD model was established via a 21-day protocol of irregular feeding, tail clamping, and forced swimming. Animals were then treated with three extract types (aqueous, ethanol, volatile oil) of CER or CGE for 14 days (n=8 per group). Therapeutic effects were assessed by gastric emptying rate, small intestinal propulsion rate, and serum levels of motilin, gastrin, and somatostatin. Chemical profiling of the aqueous extracts was performed using UPLC-Q-TOFMS, and network pharmacology predicted bioactive components, core targets, and key pathways. RESULTS: All CER extracts significantly alleviated FD symptoms, with the aqueous extract (JS) showing the most comprehensive efficacy, improving all motility and hormonal parameters. In contrast, CGE extracts produced only partial or non-significant improvements. Chemical analysis revealed CER's unique enrichment in polymethoxyflavones and limonoids, which were scarce in CGE. DISCUSSION: Network pharmacology predicted that these distinct components in the CER coregulate a network centered on targets such as OPRM1 and PTGS1, significantly enriching pathways related to the neuroactive ligand-receptor interaction and the serotonergic synapse-key systems in brain-gut axis regulation. CGE's mechanism appeared more associated with broad inflammatory pathways. This study's findings are limited to a rat model and require further validation. CONCLUSION: CER, particularly its aqueous extract, demonstrates superior efficacy over CGE in treating FD. This advantage is chemically attributed to its abundance of polymethoxyflavones and limonoids and is predicted to involve multi-target modulation of the brain-gut axis, providing a scientific rationale for the preferential use of CER in FD management.
Liu et al. (Tue,) studied this question.