**9. Antibacterial activity**

The broad-spectrum of antimicrobial activity of honey was demonstrated in various studies and reportedly exerts both bacteriostatic and bactericidal activities. The antimicrobial nature of honey depends on different factors acting singularly or synergistically, the most significant of which are phenolic compounds, pH of honey, H<sup>2</sup> O2 , wound pH, and osmotic pressure exerted by the honey itself [15, 46]. The antibacterial capabilities of different unifloral Chilean honey, including ulmo honey (*E. cordifolia*), quillay honey (*Q. saponaria*), avellano honey (*G. avellana*), and tiaca honey (*C. paniculata*) were analyzed (**Table 2**). The methanolic extract of these honeys, obtained using Amberlite XAD-2 column, demonstrated better antibacterial capabilities than the honeys themselves, indicating an important role of the phenolic compounds in this activity. In *in vitro* assays, all of the honey extracts were able to inhibit the growth of *Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus*, and *Streptococcus pyogenes* determining minimal bactericidal concentration [4, 11].


**Table 2.** Review of antioxidant and antibacterial activity in unifloral Chilean honey.

The manuka honey derived from the manuka tree (*Leptospermum scoparium)*, which grows as a shrub, or a small tree throughout New Zealand and eastern Australia is the best known of the honeys. It has been reported to have an inhibitory effect on around sixty species of bacteria, including aerobes and anaerobes, positives, and Gram-negatives. The antimicrobial activity exhibited against pathogenic bacteria such as *S. aureus* make this honey a promising functional food for the treatment of wounds. The potential of honey to assist with wound healing has been demonstrated repeatedly and the healing properties can be ascribed to the fact that it offers antibacterial activity, maintains a moist wound environment that promotes healing, and has a high viscosity that helps to provide a protective barrier to prevent infection [47]. A study compared the antimicrobial activity of the ulmo honey with manuka honey against five strains of methicillin-resistant *S. aureus, E. coli*, and *P. aeruginosa*. The ulmo honey had greater antibacterial activity against all methicillin-resistant *S. aureus* isolates tested than manuka honey and similar activity against *E. coli* and *P. aeruginosa* using agar diffusion assay. The minimum inhibitory concentration assay showed that a lower minimum inhibitory concentration was observed with ulmo honey than with manuka honey for all five methicillin-resistant *S. aureus* isolates. For the *E. coli* and *Pseudomonas* strains, equivalent minimum inhibitory concentration was observed. Due to its high antimicrobial activity, ulmo honey may warrant further investigation as a possible alternative therapy for wound healing [14]. In Chile, ulmo honey extract has been patented for its bactericidal and fungicidal properties [48]. The document relates to uses of an extract of unifloral ulmo honey, rich in phenolic compounds, able to inhibit the *in vitro* growth of human pathogenic bacteria such as *S. aureus, P. aeruginosa, and E. coli*, in addition to exhibiting fungicidal and fungistatic activity on fungi genera *Mucor, Rhizopus, Aspergillus, Candida*, and *Penicillium*.

**9. Antibacterial activity**

72 Honey Analysis

concentration [4, 11].

Quillay honey (phenolic

Quillay honey (entire honey and phenolic extracts)

Ulmo, quillay avellana and

tiaca honeys

extracts)

The broad-spectrum of antimicrobial activity of honey was demonstrated in various studies and reportedly exerts both bacteriostatic and bactericidal activities. The antimicrobial nature of honey depends on different factors acting singularly or synergistically,

and osmotic pressure exerted by the honey itself [15, 46]. The antibacterial capabilities of different unifloral Chilean honey, including ulmo honey (*E. cordifolia*), quillay honey (*Q. saponaria*), avellano honey (*G. avellana*), and tiaca honey (*C. paniculata*) were analyzed (**Table 2**). The methanolic extract of these honeys, obtained using Amberlite XAD-2 column, demonstrated better antibacterial capabilities than the honeys themselves, indicating an important role of the phenolic compounds in this activity. In *in vitro* assays, all of the honey extracts were able to inhibit the growth of *Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus*, and *Streptococcus pyogenes* determining minimal bactericidal

O2

Montenegro et al. [11]

Bridi et al. [45]

Sherlock, et al. [14]

Montenegro and Ortega [48].

Schencke, et al. [49–51]

Calderon et al. [52]

Giordano et al. [22]

, wound pH,

the most significant of which are phenolic compounds, pH of honey, H<sup>2</sup>

**Floral Origin Antioxidant/Antibacterial activities Reference**

Ulmo honey Comparison of the antimicrobial activity of

*Pseudomonas aeruginosa*.

Ulmo honey (phenolic extracts) Inhibition of *in vitro* growth of human pathogenic

and *Penicillium*

guinea pig.

Ulmo honey Clinical trial: topical treatment using ulmo honey

Corcolen honey Oxygen radical absorbance capacity (ORAC-PGR),

**Table 2.** Review of antioxidant and antibacterial activity in unifloral Chilean honey.

Ulmo honey Ulmo honey topical application supplemented with

Antibacterial activity against *Pseudomonas aeruginosa, Escherichia coli, Staphylococcus typhi, S. aureus, Streptococcus pneumoniae, Vibri cholerae* and antifungal activity against *Candida albicans*.

Oxygen radical absorbance capacity (ORAC-PGR) index related to the capacity of the sample to remove peroxyl and alkoxyl radicals

ulmo and manuka honey against methicillinresistant *Staphylococcus aureus, Escherichia coli* and

bacteria *Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli* and fungicidal activity on fungi genera *Mucor, Rhizopus, Aspergillus, Candida*

ascorbic acid improves regeneration in burns in

associated with oral ascorbic acid showed excellent clinical results for the healing of venous ulcers

index related to the capacity of the sample to remove peroxyl and alkoxyl radicals

Ferric reducing antioxidant power Montenegro et al. [11]

The use of ulmo honey in association with oral vitamin C as an alternative in healing treatment of *burn wounds* in guinea pigs (*Cavia porcellus*) improves regeneration in this type of wound and also reduces the possibility of infection, inflammation, and edema [49–51]. In addition, the clinical effect of topical treatment with ulmo honey associated with oral vitamin C in patients with venous ulcers was evaluated. This treatment method presented significant results, healing wounds faster in 100% of patients with all types of venous ulcers. Furthermore, the honey presented nonadherent and debriding properties was straightforward to apply and remove, and was well received by users [52].

Regarding honey of *Q. saponaria*, the antibacterial and antifungal activities were analyzed. Extracts of unifloral honeys of quillay were tested for antibacterial activity on *P. aeruginosa, E. coli, Staphylococcus typhi, S. aureus, Streptococcus pneumoniae* type β, and *Vibrio cholerae*, and antifungal activity against *Candida albicans*. The best *in vitro* activity of these extracts were on *S. aureus* and hemolytic *S. β*, both of which affect the skin [13]. The antibacterial effects exhibited could be related to an overall effect of the phenolic compounds present in the extract (caffeic, coumaric and salicylic acids, the flavanone naringenin and the flavonol kaempferol), which were detected by high-performance liquid chromatography.

Microbial resistance to honey has never been reported which makes it a very promising topical antimicrobial agent against the infection of antibiotic-resistant bacteria and in the treatment of chronic wound infections that do not respond to antibiotic therapy. The potency of honey, such as Chilean honey, against microorganisms suggests its potential to be used as an alternative therapeutic agent in certain medical conditions, particularly wound infection.
