Integrating network pharmacology and in vivo experimentation to investigate the antiulcer mechanism of Coix lacryma-jobi

Coix lacryma-jobi L., Poaceae, is traditionally used for the treatment of gastrointestinal disorders, yet its gastroprotective and ulcer-healing properties remain poorly explored. This study, integrating network pharmacology, in vivo assays, and molecular docking, demonstrates that the hydroalcoholic extract of C. lacryma jobi exerts its effects through convergent antioxidant, anti-inflammatory, and cytoprotective pathways. In ethanol-induced acute gastric injury, extract of C. lacryma jobi (100 mg/kg) prevented the depletion of reduced glutathione levels and decreased myeloperoxidase activity. Histological and histochemical analyses confirmed preservation of gastric mucosal structure. In addition, the reversal of extract of C. lacryma jobi protective effects by pretreatment with N-ethylmaleimide, indomethacin, and Nω-nitro-l-arginine methyl ester (l-NAME) indicates the involvement of sulfhydryl groups, prostaglandins, and nitric oxide pathways in its gastroprotective mechanism. In chronic acetic acid–induced ulcer, extract of C. lacryma jobi not only reduced the ulcerated area but also produced clear histological improvement, characterized by re‑epithelialization, reorganization of mucosal layers, and partial restoration of glandular architecture. These activities are likely related to decreased levels of reduced glutathione, lipid hydroperoxides, and diminished myeloperoxidase activity. Network pharmacology analyses indicated that the bioactive constituents of extract of C. lacryma jobi primarily exert their effects by modulating inflammatory signaling pathways. Mass spectrometry identified polyphenols, among which quercetin and kaempferol exhibited the highest binding affinity to myeloperoxidase and to IL-1β in docking simulations. Furthermore, no evidence of toxicity was observed in vivo and in silico assays for extract of C. lacryma jobi and its bioactive compounds. Collectively, these findings demonstrate that extract of C. lacryma jobi exerts multi-target gastroprotective and healing effects, supporting its potential as a natural antiulcer agent.