Effects of Rutaecarpine on Chronic Atrophic Gastritis Through Nucleotide-binding Oligomerization Domain-like Receptors and Inflammasomes

Abstract

Objective: Chronic atrophic gastritis (CAG) is a complex and burdensome disease. However, side effects and compliance issues cannot be ignored due to the long treatment cycle. Numerous studies have confirmed the effectiveness of rutaecarpine (RUT) for treating digestive dysfunction. However, the potential mechanism of action of RUT in the context of CAG treatment remains unclear. This study aimed to explore the therapeutic effects and mechanisms of RUT in 1-methyl-3-nitro-1-nitrosoguanidine-induced CAG using network pharmacology, metabolomics, and traditional pharmacological approaches. Materials and Methods: Pathological tests and ELISA assays were used to observe the therapeutic effects of RUT treatment on CAG. Differential metabolites were identified using ultra-high-performance liquid chromatography-tandem mass spectrometry, and metabolism-related target genes were enriched. The same target genes were identified between RUT and CAG diseases. The intersectional target genes were uploaded to Cytoscape for enrichment, and the nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway was selected to validate the mechanisms of the study. Finally, cell pyroptosis status was evaluated using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, and the expressions of associated proteins of the NOD-like receptor signaling pathway were assessed by Western blotting and immunohistochemistry. Results: RUT alleviated gastric mucosal damage and significantly downregulated indicators associated with inflammation and gastric atrophy. A total of 29 intersection target genes was identified, and core pathways were obtained. The NOD-like receptor signaling pathway and pyroptosis status were selected to validate the mechanisms of RUT treatment in CAG rats. The expression of NOD-related proteins and downstream factors was downregulated in the RUT group. Conclusions: RUT exerts a pharmacological effect on relieving gastric damage in CAG rats by inhibiting NOD-like receptors and inflammasomes.

Keywords

• chronic atrophic gastritis
• inflammasome
• nucleotide-binding oligomerization domain-like receptors
• pyroptosis
• rutaecarpine