## 6 Latest Advances of Honey Applications in Wound Care  
Honey and other bee products have been known for centuries for their beneficial properties on several diseases and have been extensively used in traditional medicine, alone or in association with other therapeutic regimens [5]. The treatment of burn lesions is amongst the numerous honey ethno-pharmacological applications, and they are worthy of mention for their relevance to the aim of this paper. The rationale for this usage has been illustrated in a 2015 Cochrane review that highlighted that the healing time for partial thickness burns medicated with honey bandages is 4 to 5 days shorter than with conventional dressings medication (high-quality evidence). Similarly, an expedited outcome is observed on post-surgical infected wounds when treated with honey rather than with antispetic rinses plus gauze application, with fewer side effects (moderate-quality evidence) [113]. A 2017 Cochrane review comparing different antispetics for the treatment of burns stated that burn injuries tend to heal faster with honey treatments than if treated with topical antibiotics (moderate certainty) or non-antibacterial unconventional medicaments (high certainty) [114]. Most of the studies summarised in these review papers were conducted using Manuka honey, but since this review, other honey varieties and bee products have also been investigated and their beneficial effects disclosed. For example, the association of chestnut honey and RJ into an ophthalmic formulation promoted corneal healing of a chemical burn model on rats. This was also confirmed by the significantly increased levels of \(\alpha\beta\beta\)1-integrin on histological sections after two weeks of treatment [115]. A synergistic effect with natural products of different origin has also been reported for honey promotion of burn healing. For example, mixtures of Euphoria honey and _A. sativum L._ in different proportions were found to be more effective compared to conventional treatment such as silver sulfadiazine and betadine, functionally reducing the time needed to achieve epithelialisation and burn wound contraction, with no side effects such as allergic reactions [116]. A synergistic effect, as increased inhibition zone in vitro, has also been observed for honey combined with antimicrobial drugs, suggesting a possible use of honey as a complementary aid to conventional antibiotics in wound treatment [78]. Furthermore, supplementation of honey with propolisis extract has been shown to improve honey s antimicrobial activity with synergistic effect [117]. An additive effect was instead observed in the scratch assay with a more significant wound closure compared to control. It has been hypothesised that these increased beneficial effects of honey might be explained by the improved antioxidant and anti-inflammatory activity upon propolisis extract addition [118]. Another mechanism responsible for the ability to promote wound healing could be the propolisis-mediated increased expression of AQP3 and consequent augmented Ca2+, a mechanism also observed in honey [87], as described earlier in this review. These encouraging results show that honey and bee products of different botanical origins can be employed to promote more rapid healing and to effectively treat infections that colonize burns complicating skin recovery. Therefore, it can be concluded from the latest studies that honey application represents a valuable natural approach in the treatment of burns, both alone or in association with alternative or conventional medicaments. In the field of wound medicine, Diabetic Foot Ulcers (DFU) are currently a critical challenge with an alarming estimated incidence in 15% of diabetic patients, resulting in a dramatic compromise of their quality of life and high mortality [119; 120]. Microbial infections represent the main complication, particularly given the insurance of antibiotic-resistant strains together with impaired wound healing, and the aggravation of symptoms can often result in limb amputation [121].