## 4 Antimicrobial Properties of Honey
This inherent acidity is deemed to be one of the primary contributors, for the antimicrobial activity of honey as it creates an unfavourable environment for bacterial growth [82]. However, no correlation between pH and antibacterial activity was found in Stingless bee honeys [83] nor in Polish honeys against Staphylococcus cocci [84]. The acidity is also believed to play a role in the capacity of honey to restore the skin barrier properties that can be affected by various medical conditions. Inflammatory diseases (atopic prone skin, eczema, seborrheic dermatitis), skin microbiome alteration, topical infections (candidiasis), and wounds can in fact compromise the epidermal acidic milieu [85]. The use of topical agents with slightly acidic pH, such as honey, can helpestablish and maintain skin physiological pH (in the range between 4.5 and 6.0) and the re-deposition of the \"acid mantle\" which is important for optimal skin barrier function in the stratum corneum (the outermost epidermal layer) [86]. Topical treatment with honey can also enhance wound healing by creating an unfavourable environment for proteolytic enzymes, such as elastase or matrix metalloproteinases (MMPs). These are otherwise found to be hyperactive in the alkaline environment typical of chronic and infected wounds (up to 7.5-8.9), and as a consequence of this, the skin repair is impaired by the continuous degradation of recently deposited tissue [85]. Another suggested mechanism for the widely clinically observed capacity of honey to fight bacterial infections and promote skin regeneration is due to the production of hydrogen peroxide (H\({}_{2}\)O\({}_{2}\)) during the glucose oxidase (GOx)-mediated conversion of glucose to its correspondent acid. Furthermore, honey also upregulates AQP3 aquaporin's expression, with consequent improved diffusion of H\({}_{2}\)O\({}_{2}\), which results in increased calcium Ca\({}^{2+}\) cytoplasmatic levels by Ca\({}^{2+}\) channels activation. Different Ca\({}^{2+}\) release intensities and kinetics have been linked to different honey varieties. Augmented intracellular Ca\({}^{2+}\) thereupon governs numerous biochemical chains of events that ultimately boost wound repair [87]. However, conflicting results are reported in the literature about the role played by H\({}_{2}\)O\({}_{2}\) in the antibiotic efficacy of honey, and this might also due to the time-sensitive variations of H\({}_{2}\)O\({}_{2}\) levels after honey production. H\({}_{2}\)O\({}_{2}\) content in Western Australian honeys did not show a correlation with the antiseptic performance, although H\({}_{2}\)O\({}_{2}\) reduction operated by the enzyme catalase did affect the samples' antimicrobial power [88]. Comparable results to these reported by [PERSON] et al. were also described by [PERSON] and co-workers about honeydew honeys with no significantly different results in the antibacterial in vitro evaluations, despite divergent H\({}_{2}\)O\({}_{2}\) concentrations across the samples [76]. On the other hand, opposite observations were collected by the same author in an attempt to elucidate the contribution of H\({}_{2}\)O\({}_{2}\) to the antimicrobial effect of different blossom honeys--namely rapeseed, acacia and wildflower, which were ordered here by increasing antibacterial activity. In fact, [PERSON] et al. reported a statistically significant correlation between antibacterial effect and both total phenolic and H\({}_{2}\)O\({}_{2}\). However, interestingly, no statistical correlation was registered between the measured H\({}_{2}\)O\({}_{2}\)-producing enzyme GOX and the levels of H\({}_{2}\)O\({}_{2}\). Furthermore, while again dramatically inhibited by treatment with catalase, such antimicrobial activity was instead not affected when GOx was proteolytically digested upon the addition of proteinase K [44]. These results suggest that another system, other than the protein-controlled one, must be co-responsible for the honey peroxide-mediated activity.