Artemisia vulgaris and sabinene ameliorate gastric ulceration and its recurrence through modulation of acid secretion, oxidative stress, and inflammatory cytokines: an in vivo and in silico study.
TL;DR
HEAv and sabinene exert gastroprotective and healing effects by modulating acid secretion, oxidative stress, and inflammatory cytokines, as suggested by in silico analyses.
Abstract
ETHNOPHARMACOLOGICAL
Importance
Artemisia vulgaris L., popularly known as mugwort, is traditionally used to treat gastric disturbances, yet the mechanistic basis of its antiulcer effects is largely unexplored.
Aim
OF THE STUDY The study evaluated the gastroprotective, healing, and anti-recurrence effects of the hydroalcoholic extract of A. vulgaris (HEAv) and its constituent sabinene, and their underlying pharmacological mechanisms.
Materials And Methods
Phytochemical analysis of HEAv used LC-MS, LC-MS/MS, and LC-ESI-IT-MSn. Gastroprotective activity of HEAv (3, 10, or 30 mg/kg) and sabinene (3 mg/kg) was assessed in ethanol- and piroxicam-induced ulcers, beyond pyloric ligation. Healing and recurrence were assessed via acetic acid-induced and IL-1β-triggered ulcers, the latter monitored by ultrasonography. Oxidative stress, inflammatory markers, histology, network pharmacology, and molecular docking/dynamics were evaluated, along with acute toxicity in mice.
Results
Chemical analysis identified 36 compounds in HEAv, predominantly phenolics and flavonoids. HEAv and sabinene showed gastroprotective effects, corroborated by mucosal protection and modulation of oxidative stress and inflammatory parameters. In addition, HEAv increased gastric pH, compared to omeprazole. Moreover, HEAv and sabinene reduced ulceration in both the healing and recurrence models, accompanied by increased GSH and CAT activity, and reduced LPO, MPO, and pro-inflammatory cytokines (IL-6 and IL-17A). No acute toxicity was observed. Network pharmacology identified inflammatory signaling as a key target of HEAv constituents, and docking and dynamic molecular assays confirmed favorable, stable interactions between phenolic compounds and sabinene with H+/K+-ATPase and IKKβ, supported by favorable MM-PBSA/MM-GBSA binding energies.
Conclusion
HEAv and sabinene exert gastroprotective and healing effects by modulating acid secretion, oxidative stress, and inflammatory cytokines, as suggested by in silico analyses. Nonetheless, further studies are warranted to validate the predicted molecular targets and to elucidate additional pharmacological pathways.