Populus nigra Bud Extract as a Standardized Alternative to Propolis: Evidence of Compositional Similarity-Functional...

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.