In order to evaluate the immunomodulatory potential of novel monofloral Irish honeys, THP-1 monocyte-derived macrophages provided a suitable cell-based model. THP-1 cells can be differentiated to macrophages using phorbol-12-myristate-13-acetate (PMA). Differentiated cells are then challenged with lipopolysaccharide (LPS) to stimulate the inflammatory cascade. Few studies on the cytotoxic concentrations of these two compounds on THP-1 cells have been published. Therefore, the viability of treated THP-1 cells was initially evaluated using Trypan Blue dye exclusion (for PMA), the resazurin assay (for LPS), and propidium iodide (PI) staining (for both). The literature suggests that concentrations ranging from 100 ng/mL down to 5 ng/mL PMA are sufficient for THP-1 differentiation. Consequently, further elucidation of the differentiation potential of this sub-cytotoxic PMA concentration range was also evaluated using flow cytometric detection of the macrophage-specific CD14 cell surface marker.

Honey has been recognised for centuries for its potential therapeutic properties, and its application in wound healing has gained attention due to its antimicrobial, anti-inflammatory, and regenerative properties. With the rapid increase in multidrug resistance, there is a need for new or alternative approaches to traditional antibiotics. This paper focuses on the physicochemical changes that occur when formulating honey into Pluronic F127 hydrogels. The manual incorporation of honey, irrespective of quality type, presented the amelioration of Pluronic’s capacity to undergo sol–gel transitions, as investigated by parallel plate rheology. This novel finding was attributed to the formation of fractal aggregates via the hydrogen-bonding-induced irreversible aggregation of honey–PF127 micelles, which subsequently dominate the entire hydrogel system to form a gel. The hydrogen bonding of micelles was identified through Attenuated Total Reflectance Fourier-Transform Infrared Spectroscopy (ATR-FTIR), Differential Scanning Calorimetry (DSC), and Dynamic Light Scattering (DLS). This is the first known study to provide physicochemical insight into the effects that honey incorporation has on the thermogelation capacity of Pluronic F127 hydrogels for downstream dermal wound applications.

Honey has long been valued for its medicinal properties, yet the therapeutic potential of Irish monofloral honey remains largely unexplored. This study investigates the antioxidant and immunomodulatory effects of Irish ivy (Hedera helix) and heather (Calluna vulgaris) honey samples on PMA-differentiated THP-1 macrophages, a well-characterised immune model. Antioxidant capacity was assessed through free radical scavenging assays, DPPH and ORAC, while qPCR analysis examined the key inflammatory markers. Both the heather and ivy honey varieties demonstrated antioxidant activity, with heather honey exhibiting the highest total phenolic content (TPC), and ivy honey stimulating Nrf2 activation. Manuka honey showed the strongest radical scavenging capacity, as reflected in its higher ORAC and DPPH values. These findings suggest that the different honey varieties may exert antioxidant effects through distinct mechanisms. Exposure to honey reduced oxidative stress and upregulated the expression of a key antioxidant transcription regulator (Nrf2) and an associated downstream antioxidant defence enzyme, superoxide dismutase (SOD). Additionally, both the honey types exhibited immunomodulatory effects, upregulating pro-inflammatory cytokines, such as TNF-α and IL-1β, while increasing the expression of the anti-inflammatory cytokine IL-10. These findings suggest potential bioactive properties that warrant further investigation. Given the growing interest in alternative treatments for inflammation-related conditions, further research is warranted to determine whether the observed in vitro effects translate into clinically relevant outcomes. This study expands the current understanding of Irish monofloral honey, reinforcing its potential as a functional bioactive compound with relevance in antioxidant therapies, immune modulation, and wound healing.