Anti-Diabetic Potential of the American Mistletoe Phoradendron brachystachyum: In Vitro and In Silico Approach

The anti-diabetic potential of Phoradendron brachystachyum was evaluated through the assessment of the cellular antioxidant, anti-inflammatory, and glucose uptake-modulating activities of its non-digested (ND) and digested (D) extracts from leaves (L), stems (S), and whole aerial parts (WAP). The WAP non-digested extract exhibited the highest cellular antioxidant activity, with a 99% inhibition of reactive oxygen species in Caco-2 cells, and a significant reduction in nitric oxide production in RAW 264.7 cells. Crucially, in an insulin-resistant HepG2 cell model, the WAP extract significantly increased glucose consumption to 82.67%, retaining high bioactivity (66.55%) even after the digestion process. UPLC-MS analysis identified quercetin-3-O-rhamnoside as the most abundant in all extracts. Complementary the in silico molecular docking and 100 ns molecular dy-namics simulations identified spiraeoside and quercetin-3-O-alpha-L-rhamnopyranoside as potent α-glucosidase inhibitors (-9.9kcal mol-1), while sakuranetin and spiraeoside showed higher affinity for α-amylase (-9.0 kcal mol-1). These in vitro and in silico findings provide a scientific basis for the ethnopharmacological use P. brachystachyum, showing its potential to modulate glucose metabolism.