Integrated analysis of transcriptomics and proteomics reveals the ameliorative effect of processed Aucklandiae Radix on functional dyspepsia.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Processed Aucklandiae Radix (Wei Mu Xiang in Chinese, WMX), a processed product of the root of Aucklandia lappa Decne., is traditionally used to consolidate intestines and relieve diarrhea. It is clinically applied for treating diarrhea and abdominal pain caused by spleen and stomach deficiency-cold, characterized by its warm nature without causing dryness and its efficacy in regulating spleen and stomach function. However, its therapeutic mechanism concerning gastrointestinal motility in functional dyspepsia (FD) remains unclear. AIM OF THE STUDY: This study aimed to investigate the ameliorative effect of WMX on FD and to elucidate its potential mechanism of action based on integrated transcriptomic and proteomic analyses. MATERIALS AND METHODS: An FD mouse model was induced by iodoacetamide (IAA). Mice were divided into the following groups: Control, Model, Domperidone (positive control), and WMX low-, medium-, and high-dose groups. The general state of the mice was observed. Gastric emptying rate and intestinal propulsion rate were measured. Histopathological changes in the gastric antrum were assessed via HE staining. Serum levels of brain-gut peptides (MTL, Gastrin, GHRP-Ghrelin, VIP, SS, CCK) were detected by ELISA. Transcriptomics and proteomics technologies were employed, followed by validation using RT-qPCR and Western blotting, to systematically evaluate the efficacy of WMX and its impact on related signaling pathways. RESULTS: WMX significantly improved the general state of FD mice, promoted gastric emptying and intestinal propulsion, and reduced inflammatory cell infiltration in the gastric antrum tissue. Concurrently, WMX effectively modulated the FD-induced dysregulation of serum brain-gut peptide levels, increasing the levels of excitatory peptides (MTL, Gastrin, GHRP-Ghrelin) and decreasing the levels of inhibitory peptides (VIP, SS, CCK). Integrated transcriptomic and proteomic analysis revealed that the interventional effect of WMX was closely associated with immunoinflammatory regulation, identifying the NOD-like receptor signaling pathway as a key target. Experimental validation further confirmed that WMX significantly downregulated the gene and protein expression of key molecules within this pathway, including NOD1, RIPK2, ERK, IL-6, TNF-α, and IL-18. CONCLUSION: WMX ameliorates FD by regulating brain-gut peptide levels and suppressing the excessive inflammatory response mediated by the NOD1/RIPK2/ERK signaling pathway.