Objective To study the blood-entry active components and molecular mechanisms of Ferula sinkiangensis leaf aqueous extract (FSLAE) against alcoholic gastritis (AG), so as to provide a scientific basis for its medicinal development and the utilization of characteristic medicinal plant resources in Xinjiang. Methods Ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to characterize the in vitro chemical constituents of FSLAE and the blood-entry constituents of rats. The intersecting targets between blood-entry components of FSLAE and AG were screened by network pharmacology. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were applied to predict the core pathways, and molecular docking was performed to verify the binding activity of core components to key targets. The AG rat model was induced by 70% ethanol, control group, model group, FSLAE high-, medium-, low dose (150, 100, 50 mg/kg) groups and magnesium aluminum carbonate (31.5 mg/kg) group were set up, with 10 rats in each group, drugs were continuously given for 7 d. Pathological changes of gastric mucosa were observed by hematoxylin-eosin (HE) staining. Levels of tumor necrosis factor-α (TNF-α), interleukin-17A (IL-17A) and IL-6 in serum were detected by ELISA. Hepatic and pancreatic function as well as nutrition-related indicators were measured using an automatic biochemical analyzer. The expression of proteins related to the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway in gastric tissue was determined by Western blotting. Results A total of 191 in vitro chemical constituents were identified from FSLAE, among which 23 constituents were confirmed as blood-entry components, mainly including phenolic acids, coumarins, fatty acids, etc. The core active components were ferulic acid, isoferulic acid and 4-methylumbelliferone. Network pharmacology identified 148 intersecting targets between FSLAE and AG, which were significantly enriched in inflammation-related pathways such as TNF and JAK/STAT pathways, with STAT3, JAK2 and TNF as the core targets. Molecular docking verified that the binding energies of core components to core targets were all less than &8722;6 kcal/mol, indicating favorable binding activity. In vivo experiments results showed that FSLAE dose-dependently ameliorated gastric mucosal pathological injury and alleviated the lag in body weight gain in AG rats. FSLAE significantly downregulated levels of pro-inflammatory factors (TNF-α, IL-17A, IL-6) and abnormal hepatic and pancreatic function markers including alanine aminotransferase (ALT), aspartate aminotransferase (AST), amylase (AMY) and total bilirubin (TB) in serum (P < 0.05, 0.01, 0.001), upregulated levels of nutrition-related indicators such as albumin (ALB) and total protein (TP) (P < 0.05, 0.01), inhibited the phosphorylation levels of JAK2 and STAT3 in gastric tissue (P < 0.01, 0.001). Conclusion FSLAE exerts a gastroprotective effect against AG by inhibiting the excessive activation of JAK2/STAT3 signaling pathway and alleviating inflammatory responses via its blood-entry active components. Phenolic acids and coumarins serve as the core pharmacodynamic material basis.

Ferula sinkiangensis K. M. Shen leaf  /  blood-entry components  /  ferulic acid  /  isoferulic acid  /  4-methylumbelliferone  /  alcoholic gastritis  /  JAK2/STAT3 signaling pathway