Metabolite profiling, enzyme inhibition, and in silico analysis of Commiphora gileadensis oleo-gum resin

Commiphora gileadensis oleo-gum resin is traditionally used in Arabia to manage diabetes, yet its phytochemical composition and mechanisms of action remain poorly characterized. To address this gap, an integrated UHPLC-MS/MS metabolomic strategy, in vitro enzyme inhibition, and in silico modeling were applied to characterize its constituents and evaluate its biological potential. UHPLC-MS/MS analysis led to the tentative annotation of fifty-five metabolites, expanding the known chemistry of this species. The ethanolic extract inhibited α-glucosidase (IC₅₀ = 6.18 µg/mL) and α-amylase (IC₅₀ = 22.33 µg/mL), with measurable inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Phytochemical investigation afforded gallic acid, quercetin, and naringenin; quercetin showed the strongest activity across all four enzymes, naringenin was moderately active, and gallic acid was least active. Docking and MD simulations generated plausible pose-retention hypotheses for several metabolites, including procyanidin B1, quercetin, sesamin, and commiferin, across the four modeled human targets. However, since the docking targets are not species-matched to their corresponding in vitro assays, these findings should not be regarded as direct confirmation of the experimental mechanism. Collectively, the findings establish the presence of a chemically diverse resin with in vitro enzyme-inhibitory activity and prioritize candidate metabolites for assay-matched validation. They do not establish antidiabetic efficacy, neuroprotection, synergistic action, or confirmed target engagement.