Molecular and Pharmacokinetic Rationale for the Use of Chelidonium majus L. in Wound Healing: An In Silico and In...

Wound healing involves the coordinated regulation of inflammation, angiogenesis, and extracellular matrix remodeling, processes modulated by natural bioactives. In this context, Chelidonium majus L. (C. majus), a plant rich in alkaloids and flavonoids, remains mechanistically underexplored. This study, therefore, investigates its metabolites using an integrated computational-experimental approach and evaluates their applicability in sericin-based wound-healing systems. A curated database of 83 C. majus bioactive compounds was analyzed using cheminformatics and molecular docking against key wound-healing targets (iNOS, VEGF, MMP-3, and tyrosinase), followed by ADMET and toxicity prediction (StopTox). Selected plant-sericin formulations were subsequently evaluated for wound-healing activity using an in vitro fibroblast scratch assay. Docking revealed strong binding affinities for several metabolites, particularly protopine, kaempferol-3-rutinoside, cynaroside, hesperidin, quercetin-3-rhamnosylrutinoside, and vitexin, indicating multi-target modulation across inflammatory, proliferative, and remodeling phases of tissue repair. ADMET and toxicity analyses predicted favorable dermal safety and pharmacokinetic profiles for most compounds. Consistently, in vitro assays demonstrated that C. majus-sericin systems had fibroblast migration and wound closure in a concentration- and ratio-dependent manner, with improved healing kinetics observed at 150 µg/mL and for formulations containing higher relative proportions of both components. The experimental outcomes supported the pro-angiogenic and matrix-stabilizing mechanisms predicted in silico. Overall, C. majus metabolites exhibit polypharmacological wound-healing activity, supporting their integration into sericin-based systems as a promising strategy for topical therapies.