Multi-platform analysis reveals the material basis and therapeutic mechanism of Chen Xiang Qu decoction piece in ameliorating functional dyspepsia in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Chen Xiang Qu (CXQ) is a traditional Chinese medicinal preparation originating from the Qing Dynasty and documented in multiple classical Chinese medical texts. Composed of agarwood, sandalwood, ginger-processed magnolia bark, and Massa Medicata Fermentata, it possesses the traditional efficacy of "regulating the liver and harmonizing the stomach, strengthening the spleen and eliminating food stagnation." Clinically, it is used to treat symptoms such as chest and abdominal distension and pain, belching, and vomiting caused by liver-stomach disharmony and spleen deficiency with dampness stagnation. AIMS OF THE STUDY: The present study aims to validate CXQ's traditional application in functional dyspepsia treatment, providing modern pharmacological evidence for its clinical application. METHODS: This study first employed UPLC-Q-TOF/MS technology to conduct a comprehensive chemical composition analysis of CXQ, establishing a material foundation for subsequent pharmacodynamic and mechanism investigations. Subsequently, a rat model of FD was developed through a combination of tail pinching, physical restraint, and irregular feeding. The effects of CXQ on gastrointestinal function were evaluated by measuring rat body weight, gastric retention rate, and small intestinal propulsion rate. Additionally, Western blot analysis was performed to analyze the protein levels. Furthermore, depressive-like behaviors in rats through sucrose preference and open field tests were examined. UPLC-QQQ-MS technology was employed to quantitatively detect monoamine neurotransmitter levels in brain tissue. Network pharmacology methods were employed to predict potential targets and signaling pathways, and validated by qPCR assay and Western blot. RESULTS: 116 chemical constituents in CXQ and 10 key components in the plasma and brain tissues of rats. CXQ significantly improved gastrointestinal motility disorders in FD rats by reducing the gastric retention rate and enhancing the small intestinal propulsion rate. CXQ also downregulated the protein overexpression of CCKBR and Nesfatin-1 in gastric tissue, and effectively alleviated depressive-like behaviors. Mechanistically, 21 intersecting targets were identified through network pharmacology screening. GO and KEGG enrichment analyses identified the TNF signaling pathway as a key mechanism for CXQ treatment. CXQ attenuated duodenal inflammatory responses in FD rats through the suppression of TNF-α, NF-κB, and IL-6 mRNA levels and p-NF-κB p65 protein expression in duodenal tissues. CONCLUSION: These data suggest that CXQ ameliorates FD by restoring gastrointestinal motility and alleviating depressive-like behaviors as well as low-grade duodenal inflammation through inhibition of the TNF-α/NF-κB/IL-6 inflammatory signaling axis.