MS/MS-based molecular networking for exploring the chemical diversity of Chiliadenus montanus (Vahl.) brullo and Chiliadenus candicans (Delile) brullo and their anti-ulcer potential via modulation of Nrf2/ICAM-1 in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Chiliadenus montanus and Chiliadenus candicans are two closely related species that are traditionally used for treating gastric ailments and peptic ulcers; however, their therapeutic efficacy lacks scientific validation.

AIM OF THE STUDY: This study aims to investigate the gastroprotective potential of both species through comprehensive metabolite profiling, in-vivo biological evaluation, and molecular docking studies.

METHODS

Methylene chloride: methanol (1:1) and 70% methanolic extracts from the aerial parts of both C. montanus and C. candicans are subjected to ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) analysis. After this, the gastroprotective efficacy of the extracts is evaluated in an ethanol-induced gastric ulcer model in rats at 200 and 400 mg/kg. Histopathological examination of gastric tissue for all extracts and molecular docking study for the most active extract was established.

RESULTS

UPLC-HRMS/MS allowed for the annotation of 217 metabolites, with only 30 metabolites previously reported in the studied species, and one potentially new compound annotated as dihydroxy costic acid O- caffeic acid hexoside, reported for the first time. Both plant extracts significantly attenuate ulcer indices and mitigate gastric inflammation through modulation of the Nrf2/ICAM-1 signaling pathway. Additionally, the extracts demonstrate potent antioxidant and anti-inflammatory activities.

CONCLUSION

Both C. montanus and C. candicans show outstanding ulcer protective potential; these effects are attributed to high content of cinnamic acid derivatives, flavonoids, and terpenoid constituents as shown through LC/MS analysis. These findings provide scientific evidence for its traditional use as an herbal tea in the treatment of gastric ulcers by Bedouins in Saint Catherine.