## 4 Therapeutic Effects of Honey
### Antibacterial Effects
(2020) [164] revealed how vitamin C supplementation can amplify the antimicrobial potential of honey against _Pseudomonas aeruginosa_ and _Escherichia coli_ in a dose-dependent manner, but also against _Staphylococcus aureus_ and _Enterococcus faecalis_ at a higher concentration of vitamin C (100 mg/g honey). However, the antimicrobial and antibacterial effects of honey are a result of the symbiosis of all these factors [143], especially between hydrogen peroxide and phenolic substances, since the presence of hydrogen peroxide alone is not considered sufficient to demonstrate antibacterial effects in honey [165]. Other studies have shown, similarly, that the content of H\({}_{2}\)O\({}_{2}\) cannot necessary be correlated with the antibacterial activity, as some honey varieties with high antibacterial potential had a low content of H\({}_{2}\)O\({}_{2}\)[166; 167; 81]. As a result, even if the presence of H\({}_{2}\)O\({}_{2}\) is compulsory for antibacterial activity, some other compounds play a key role in increasing this healing potential [168]. Moreover, the bee Defensin-1 is reported to have the same synergistic antibacterial effect with H\({}_{2}\)O\({}_{2}\)[65] as it cannot neutralise the presence of bacteria alone. A recent study revealed the antibofilm activity of Eucalyptus honey depends on the combined action of osmotic activity, H\({}_{2}\)O\({}_{2}\) and Def-1 [108]. The antibacterial mechanism of various honey types against the most common types of Gram-positive (_Bacillus cereus_, _Enterococcus faecalis_, _Listeria monocytogenes_, _Staphylococcus aureus_) and Gram-negative bacteria (_Escherichia coli_, _Pseudomonas aeruginosa_, _Salmonella enterica Serovar Typhimurium_, _Salmonella enteritidis_, _Salmonella Typhini, Salmonella Typhimurium_) or yeast (_Candida albicans_) have been widely described in Table 2, along with the most recurrent methods to determine the minimum inhibitory concentrations (MIC), the minimum bactericidal concentration (MBC). The results of antibacterial activities in honey samples investigated from different geographical areas and having different botanical origins have shown variable antibacterial effects against the tested bacteria in the presence of differing concentrations of honey. Among all tested bacteria, the most sensitive strains were _S. aureus_, _B. cereus ATCC 14579_, _L. monocytogenes ATCC 7644_ (Gram-positive) reported in [PERSON] et al. (2019) [81], [PERSON] et al. (2015) [134] and [PERSON] et al. (2020) [145], while the most resistant Gram-positive bacteria were _S. aureus ATCC 25923 and _S. aureus CCM 4223_ in [PERSON] et al. (2019) [41] and [PERSON] et al. (2020) [144]. Conversely, for Gram-negative bacteria, the most resistant were _E. coli_, _Sal. typhi ATCC 14028, P. aeruginosa ATCC 27853_ and _P. aeruginosa CCMI960_ related to [PERSON] et al. (2015) [139], [PERSON] et al. (2015) [134], [PERSON] et al. (2018) [157] and [PERSON] et al. (2019) [81], whereas the most susceptible Gram-negative strains were manifested in the studies of [PERSON] et al. (2018) [157] (_E. coli ATCC 25922_) and [PERSON] et al. (2019) [41] (_E. coli ATCC 25922_). Given the importance that antibiotic resistance of bacteria shows lately, honey can be considered an alternative antibacterial agent [170]. Furthermore, side effects of honey utilisation as complementary therapy should be still investigated within in-vivo studies [46].