Study on the Gastroprotective Mechanism of Atractylodes Japonica Koidz. Ex Kitam Against Acetic Acid-Induced Gastric Ulcer in Rats by Metabolomics

Ethnopharmacological relevance: Atractylodes japonica Koidz. ex Kitam. (A. japonica, Chinese name: Guan-Cangzhu, Japanese name: Byaku-jutsu), a perennial herb, which is mainly distributed in northeast area of China, it has the effect of invigorating the spleen and drying dampness, sweating and relieving exterior syndrome, and often used to treat digestive diseases such as gastric ulcer(GU). However, the mechanism of its potential protective action against GU remains unclear.The aim of the study: The aim of this study was to investigate the gastroprotective effects of A. japonica on acetic acid-induced GU rats.Materials and methods: The rat model of gastric ulcer was simulated by acetic acid method. The pathological changes of gastric tissues were evaluated by hematoxylin-eosin (H&E) stain, the levels of Epidermal Growth Factor (EGF), Epidermal Growth Factor Receptor (EGFR), Nuclear Factor Kappa-B (NF-κB), Interleukin-1β (IL-1β), Interleukin-10 (IL-10), Na+-K+-ATPase (NKA) in serum and gastric tissues were determined by enzyme-linked immunosorbent assay (Elisa), and the mRNA expressions of EGFR, NF-κBp65, IkappaBalpha (IκBα) and Zonula Occludens-1 (ZO-1) in gastric tissues were determined by real-time reverse transcription polymerase chain reaction (RT-PCR), and the efficacy was observed. Then, plasma metabolomic analysis was performed by UPLC-MS/MS to screen the specific potential biomarkers, metabolic pathways and to explore the possible mechanisms.Results: The results revealed that A. japonica significantly improved the pathological damage of gastric tissues, increased the expression levels of anti-inflammatory factors, decreased the expression levels of proinflammatory factors and restored the levels of factors associated with ulcer healing. Metabolomic analysis identified 10 potential differential metabolites and enriched 7 related metabolic pathways.Conclusion: These findings contribute to the understanding of the potential mechanism of A. japonica to improve acetic acid-induced GU, and will be of great importance for the development and clinical application of A. japonica.