Assessment of the Polyphenolic Profile and Beneficial Effects of Red and Green Propolis in Skin Inflammatory Conditions and Oxidative Stress

<b>Background/Objectives:</b> Propolis is a complex natural product with long-standing traditional use as an antimicrobial remedy. Several studies suggest that Brazilian varieties of propolis may promote wound healing and protect the skin from UV damage, most likely due to antioxidant and anti-inflammatory mechanisms. However, the literature provides limited support for this topic. The present work aimed at characterizing the polyphenolic profile of two Brazilian propolis samples, investigating their biological activity. <b>Methods:</b> Biological experiments were conducted in human keratinocytes (HaCaT) and fibroblasts (HDF) stimulated by cytokines involved in skin inflammation and remodeling (TNF-α and IL-1β), while phytochemical analyses were conducted by LC-MS techniques. <b>Results:</b> Our findings indicate that artepillin C and drupanin were the principal phytochemicals of green propolis, while vestitol, medicarpin, and neovestitol were the most abundant in red propolis. The presence of phenolic compounds was correlated with the antioxidant activity demonstrated by ORAC and intracellular ROS assays. Accordingly, both Brazilian propolis samples impaired NF-κB activity, while only red propolis hindered IL-8 release in both cell lines with an IC₅₀ lower than 25 μg/mL. Surprisingly, both propolis samples at the same concentrations enhanced the production of IL-6 and VEGF, thus suggesting the coexistence of anti-inflammatory, antioxidant, and trophic mechanisms contributing to skin repair. In line with this hypothesis, propolis also induced the stabilization of HIF-1α, paralleling the biological effect of a well-known synthetic HIF stabilizer (DMOG). <b>Conclusions:</b> This work supports the investigation of Brazilian red and green propolis as potential modulators of the inflammatory phase in wound healing.