Populus nigra Bud Extract as a Standardized Alternative to Propolis: Evidence of Compositional Similarity—Functional Properties of an Oral Spray Containing Populus nigra Bud Extract

Populus nigra buds contain resinous exudates rich in flavonoids, phenolic acids, terpenoids and other bioactive constituents. These exudates are the main botanical source of European Poplar-type propolis. Since hive-collected propolis shows strong botanical, geographical and hive contaminant variability, P. nigra bud resin exudate represents an attractive, standardizable and reproducible alternative for obtaining natural-complex ingredients. This study investigates the compositional relationship between Propolgemma® standardized P. nigra buds (PBHE) and European propolis (PHE) hydroalcoholic extracts through integrated analytical approaches and evaluates the functional bioactivity of PBHE and a related oral spray formulation (Propolgemma® spray forte, PBHE-SF). Untargeted metabolomic fingerprinting revealed clear clustering of P. nigra bud exudate with European propolis, demonstrating high compositional similarity. Targeted analyses confirmed that PBHE belongs to the poplar-type propolis family, while retaining additional bud-derived constituents such as salicylates, lignins and tannins, typical of bud tissue and largely absent from hive-collected propolis. Functionally, PBHE showed concentration-dependent antioxidant activity and significant inhibition of Streptococcus pyogenes biofilm at sub-MIC levels. PBHE, incorporated into a patented oral spray formulation (PBHE-SF), demonstrated strong mucoadhesion, high resistance to salivary wash-off, retention of antioxidant flavonoids on epithelial substrates and a mechanical barrier effect, reducing LPS-induced IL-6 release by 39%. It also showed dispersion of pre-formed S. pyogenes biofilms. PBHE emerges as a reproducible, plant-derived, bee-independent alternative to European propolis. Its chemical consistency, functional reliability, independence from bee foraging and from hive-derived contaminants improve the therapeutic potential on mucosal protection in medical device formulations and the suitability for scalable, controlled and industrially sustainable production.