Qizhiweitong particles (QZWT), a classic Chinese herbal prescription derived from the
Sinisan decoction in Shang Han Za Bing Lun, has definitive clinical efficacy in treating Chronic Non-
atrophic Gastritis (CNG) in China. However, its mechanism of action at the metabolic level remains unclear. The aim of this study was to explore the mechanisms of QZWT against CNG based on non-targeted metabolomics combined with network pharmacology and experimentally validated by
enzyme linked
immunosorbent assays (ELISA). First, CNG model rats were established by free drinking
ammonia water combined with
starvation and satiety disorder for 12 weeks. Taking gastric tissue as the object, ultra-high performance liquid chromatography tandem mass spectrometry based metabolomics and network pharmacology were conducted to identify the key compounds, core targets and pathways that mediate the effects of QZWT against CNG. Furthermore, the targets from network pharmacology and the metabolites from metabolomics were jointly analyzed to select crucial metabolism pathways by MetaScape. Finally, the key metabolic
enzymes and metabolites were experimentally validated by ELISA. The results indicated that there were 29 differential metabolites were identified and considered to be metabolic
biomarkers of QZWT in the treatment of CNG. Among them, 8 of the differential metabolites showed a significant reduction in the content of QZWT groups.
Arachidonic acid (AA) metabolic and
glycerophospholipid (GP) metabolic are the most crucial metabolic pathways for QZWT to treat CNG. QZWT regulated AA and GP metabolism by synergetic reducing the level of AA,
Phospholipid acid and
Lysophosphatidic acid and inhibiting the
enzyme activity of
prostaglandin endoperoxide synthase 1 and
prostaglandin endoperoxide synthase 2. And a compound-reaction-
enzyme-gene network of mechanism for QZWT against CNG was established. In conclusion, this study reveals the complicated mechanisms of QZWT against CNG. Our work presents a novel strategy to identify the potential mechanisms of pharmacological effects derived from a compound prescription of TCM.