# Honey Therapy in Diabetic Foot Ulcers: A Promising Strategy for Effective Wound Healing
## 5 Types of Honey Effects  
Since honey's have different characteristics, depending on the botanical origin, concentration, or storage conditions, it might be expected that different honey's possess different healing properties. Importantly, multi-floral honey exhibits a greater phenolic content than monofloral honey, which confers different levels of anti-inflammatory and bactericidal activity potential [133]. The topical application of manuka honey in streptozotocin-induced Wistar rats promoted a higher percentage of wound contraction and faster epithelization than a group treated with acacia honey (_Robinia pseudoacacia_) [134]. Similarly, Japanese acacia honey was not effective in promoting complete wound epithelialization [34]. Importantly, acacia honey is characterized by a lower polyphenol content and antioxidant capacity level among Romanian honey samples [135]. Interestingly, no differences were observed in wound healing in comparisons between manuka and jamun honey (_Syzygium cumini_), which were characterized by similarly low pH levels and sugar and flavonoid contents [136]. Four hours after the topical application of different types of honey, namely manuka, kanuka, and rewarewa, in mice submitted to arachidonic-acidic-induced ear edema revealed that only rewarewa (_Kniglhea excelsa_) honey significantly reduced the edema and leukocyte infiltration when compared with the untreated negative control group [87]. Interestingly, the superoxide inhibition in vitro did not correlate with honey's phenolic content. The authors also reported an inverse correlation between manuka honey's MGO content and neutrophil superoxide production. However, this correlation was not caused by the MGO-dependent inhibition of the anti-inflammatory activity, suggesting the contamination of the manuka honey with nectar from other flower sources [87]. Similarly, Sidr honey (_Ziziphus spina-christi_) was the most effective treatment in thermal or chemical-induced wounds when compared to thymme (_Thymus vulgaris_) and spring honeys or conventional therapy [137], showing the diverse action of honey in wound healing. The healing actions of different honeys might also differ according to the stage of wound healing. The in vivo application of acacia (_Robinia pseudoacacia_), buckwheat (_Fagopyrum esculentum_), and Chinese milk vetch (_Astragalus sinicucus_) honey was effective only in the inflammatory wound healing phase [34]. Conversely, a chestnut (_Castanea sativa_) honey hydrogel applied in the excisional wounds of _db/db_ mice showed a delayed action in terms of wound closure during the first six days after wound excision [138]. Similarly, in streptozotocin-induced diabetic Wistar rats, wounds treated with mad honey only showed epithelialization and reductions in inflammatory cells similar to tetramycin treatment at the 19 th day, supporting a delayed mechanism of action in mad honey during the first days after wound excision [139]. In vitro comparisons between honey samples' bactericidal activity levels have shown that different types of honey have different mechanisms of action according to the different bacterial strains. For instance, Revamil medical-grade honey showed the highest antibacterial activity level against _E. coli_ and _P. aeruginosa_ after 2 h of incubation, whereas manuka honey was the most effective after 24 h. Against _B. subtilis_, manuka honey's bactericidal components such as MGO and its low pH were able to rapidly promote the bactericidal activity, similarly to Revamil honey after 2 h of incubation [76]. Furthermore, among the medical-grade honeys, Revamil was classified as the least effective, showing higher MIC levels, whereas Surgihoney 3 showed lower MIC levels against _S. aureus_, _MRSA_, _P. aeruginosa_, multidrug-resistant _P. aeruginosa_, _E. coli_, and _K. pneumoniae_[12]. Neither for Revamil nor for Surgihoney was information regarding the floral sources provided, hindering accurate comparisons between different types of honeys.