From Agro-Waste to Therapeutic Potential: Spasmolytic Mechanisms of Vaccinium myrtillus L. Leaf Extract on Isolated Rat Ileum

Bilberry (<i>Vaccinium</i><i>myrtillus</i> L., Ericaceae) is chiefly valued as an edible plant for its berries, widely consumed as a functional food, whereas the leaves, as agro-waste, remain an underutilized natural source of bioactives. The traditional use of <i>V. myrtillus</i> leaves is well documented, particularly for managing diabetes and gastrointestinal disorders. However, their potential spasmolytic activity, which could support such uses, remains unexplored. The main objective of this study was to evaluate the spasmolytic potential of <i>V. myrtillus</i> leaf extract on the gastrointestinal tract and to elucidate its underlying mechanism of action. The spray-dried 50% hydroethanolic extract of <i>V. myrtillus</i> leaves, obtained by double percolation, was analyzed using HPLC-DAD. The analysis revealed phenolic acids, with chlorogenic acid as the major compound, and flavonoids, predominantly isoquercitrin. Spasmolytic activity was tested on isolated rat ileum, and the mechanism of action was monitored using models of spontaneous contractions and acetylcholine-, histamine-, CaCl₂^-, Bay K8644-, L-NAME-, ODQ-, apamin-, BaCl₂^-, charybdotoxin-, glibenclamide-, TRAM-34-, and quinine-modified contractions. The extract's activity on isolated ileum strips is primarily mediated via Ca²⁺ channels, cGMP, histamine, and NO pathways. Overall, this study affirms <i>V. myrtillus</i> leaves as a valuable source of phenolic compounds with potential for treating spasmodic gastrointestinal disorders.