Phytochemical Characterization and Assessment of the Wound Healing Properties of Four “Poplar-Type” Propolis

Objectives: This study aimed to evaluate the potential of poplar-type propolis for wound healing by analyzing its phytochemical profile and biological effects. Methods: The phytochemical characterization included specific colorimetric assays to estimate the total phenolic and flavonoid contents and the triterpenoids content. Some of the main components of poplar propolis (pinocembrin, pinobanksin, CAPE, chrysin, galangin) were analyzed using HPLC-DAD. Scavenging activity and total antioxidant capacity were assessed through DPPH and ORAC assays, respectively. Biological in vitro assays used keratinocyte, fibroblast, and monocytic cell lines. The direct wound healing properties were tested through scratching assays and ELISA kits for the assessment of the production of growth factors (FGF-7, Latency Associated Peptide - LAP), while the indirect effects were evaluated through the estimation of the levels of MMP9, IL-1β, IL-8 and TNF-α using ELISA kits together with a cell-free test on the inhibition capacity on collagenases. During the study, the Network Pharmacology analysis was employed to further explore possible mechanisms of action of propolis on the healing process. Results: The analyses confirmed the high phenolic content of poplar propolis, dominated by flavonoids, and terpenes. Propolis exhibited significant antioxidant activity and interestingly, propolis showed indirect wound-healing properties by mitigating inflammation and remodeling (reduced IL-1β and MMP9) and potentially modulating the immune response (upregulated IL-8). In vitro studies confirmed these effects, demonstrating decreased MMP9 production and collagenase inhibition when cells were co-treated with propolis and a stressor. Propolis also suppressed IL-1β release in fibroblasts, although its impact on TNF-α was inconclusive. Notably, co-treatment upregulated IL-8 in monocytes, suggesting a potential immunomodulatory role. Conclusion: poplar propolis may not directly stimulate cell proliferation during wound healing, while its anti-inflammatory and immunomodulatory properties could suggest an indirect contribution to the process.