Honey, Wound Repair and Regenerative Medicine

Martinotti, Simona; Ranzato, Elia

doi:10.3390/jfb9020034

Cited by 99 publications

(90 citation statements)

References 38 publications

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“…In addition, data coming from scratch wound observations as well as from cell migration assays have shown beyond any reasonable doubt that honey produces a striking increase of the wound repair abilities of keratinocytes and fibroblasts [4]. Taken together, our previous observations consistently suggest that honey is generally active in helping wound closure, thus confirming a bulk of anecdotal and scientific evidence [5,6].…”

Section: Introductionsupporting

confidence: 75%

Honey-Mediated Wound Healing: H2O2 Entry through AQP3 Determines Extracellular Ca2+ Influx

Martinotti

Laforenza

Patrone

et al. 2019

IJMS

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Since Biblical times, honey has been utilized in “folk medicine”, and in recent decades the positive qualities of honey have been re-discovered and are gaining acceptance. Scientific literature states that honey has been successfully utilized on infections not responding to classic antiseptic and antibiotic therapy, because of its intrinsic H2O2 production. In our study, we demonstrated the involvement of H2O2 as a main mediator of honey regenerative effects on an immortalized human keratinocyte cell line. We observed that this extracellularly released H2O2 could pass across the plasma membrane through a specific aquaporin (i.e., AQP3). Once in the cytoplasm H2O2, in turn, induces the entry of extracellular Ca2+ through Melastatin Transient Receptor Potential 2 (TRPM2) and Orai1 channels. Honey-induced extracellular Ca2+ entry results in wound healing, which is consistent with the role played by Ca2+ signaling in tissue regeneration. This is the first report showing that honey exposure increases intracellular Ca2+ concentration ([Ca2+]i), due to H2O2 production and redox regulation of Ca2+-permeable ion channels, opening up a new horizon for the utilization of the honey as a beneficial tool.

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Section: Introductionsupporting

confidence: 75%

Honey-Mediated Wound Healing: H2O2 Entry through AQP3 Determines Extracellular Ca2+ Influx

Martinotti

Laforenza

Patrone

et al. 2019

IJMS

Self Cite

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“…A few studies demonstrate upregulation of matrix in response to dextrose prolotherapy or in vitro cultivation with high concentrations of glucose. Collagen expression is increased after exposure of patellar tendon fibroblasts to the prolotherapy agents P2G or dextrose 54 and thus may contribute to tissue regeneration within a cutaneous wound. Collagen type I synthesis is also increased in high-glucose cultivation of renal fibroblasts, in a TGF-b-mediated pathway.…”

Section: Discussion Of Findings and Relevant Literature The Possible mentioning

confidence: 99%

“…[63][64][65] H 2 O 2 generated by topical application of honey in the wound may also signal for reparative pathways. 66,67 Multiple honey-containing topical creams and dressings are commercially available for wound therapy, although Cochrane review of the evidence of their efficacy supports its use only in burn wounds. 68 Honey is composed of water (<20%), sugars (most commonly fructose, *76%), and a host of other components, 67 and although it is tempting to propose that some of the effects of dextrose prolotherapy are mediated by generation of H 2 O 2 in the injected tissues, there are no studies to evaluate this possibility.…”

Section: Prolotherapy Analogy To Honey?mentioning

confidence: 99%

“…66,67 Multiple honey-containing topical creams and dressings are commercially available for wound therapy, although Cochrane review of the evidence of their efficacy supports its use only in burn wounds. 68 Honey is composed of water (<20%), sugars (most commonly fructose, *76%), and a host of other components, 67 and although it is tempting to propose that some of the effects of dextrose prolotherapy are mediated by generation of H 2 O 2 in the injected tissues, there are no studies to evaluate this possibility. It may be that the use of honey for wound repair and its mechanisms could be considered a model for treatment of cutaneous wounds using prolotherapy, but laboratory studies will be needed to support this possibility.…”

Section: Prolotherapy Analogy To Honey?mentioning

confidence: 99%

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Prolotherapy: Potential for the Treatment of Chronic Wounds?

Siadat

Isseroff

2019

Advances in Wound Care

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Significance: Chronic skin ulcers, including venous, diabetic, and pressure ulcers, constitute a major health care burden, affecting 2-6 million people in the United States alone, with projected increases in incidence owing to the aging population and rising epidemic of diabetes. The ulcers are often accompanied by pain. Standard of care fails to heal *50% of diabetic foot ulcers and 25% of venous leg ulcers. Even advanced therapies do not heal >60%. Thus there is an unmet need for novel therapies that promote healing and also address the concomitant pain issue. Recent Advances: Prolotherapy involves injection of small amounts of an irritant material to the site of degenerated or painful joints, ligaments, and tendons. Multiple irritants are reported to be efficacious, but the focus here is on dextrose prolotherapy. In vitro and in vivo studies support translation to clinical use. Concentrations as low as 5% dextrose have resulted in production of growth factors that have critical roles in repair. Numerous clinical trials report pro-reparative effects of dextrose prolotherapy in joint diseases, tendon, and ligament damage, and for painful musculoskeletal issues. However, most of the studies have limitations that result in low-quality evidence. Critical Issues: The preclinical data support a role for dextrose prolotherapy in promoting tissue repair that is required for healing chronic wounds and ameliorating the associated pain. Critical issues include provision of evidence of efficacy in human chronic wounds. Another potential obstacle is limitation of reimbursement by third-party payers for a therapy with as yet limited evidence. Future Directions: Preclinical studies in models of chronic wounds would support clinical translation. As dextrose prolotherapy has some mechanistic similarities to already approved honey therapies, it may have a shortened pathway for clinical translation. The gold standard for widespread adoption would be a well-designed clinical trial.

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“…The mechanism responsible for this positive final effect include the ability to reduce inflammation and ROS production, to modulate the production of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and interleukin (IL-6) and mainly to maintain low pH values (around 3.5) [14]. Moreover, honey possesses antibacterial activity, and also stimulates keratinocytes proliferations and angiogenesis, promoting an efficacious skin-remodeling phase [15,16]. Among all of the different kinds of honeys, none before us have investigated the wound-healing properties of Calabrian honeys.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the In Vitro Wound-Healing Activity of Calabrian Honeys

et al. 2019

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The healing of skin wounds and particularly chronic wounds, such as diabetic foot ulcers, is still a clinical emergency. Despite the many therapeutic tools that are available so far, none seems to be really effective and safe. In this context, we highlighted the renewed wound healing activity of honey, a viscous aromatic and sweet food, by way of in vitro wound-healing assays, using the HaCaT cell line. Specifically, we investigated five monofloral or multifloral honeys from different Calabrian provinces using them as such or extracted (by Amberlite® or n-hexane and ethyl acetate). The chemical composition of honeys was ascertained by 1H NMR spectroscopy and by the gas chromatography/mass spectrometry (GC/MS) method for volatile organic compounds (VOCs). Amongst the five tested honeys, BL1 and BL5 honeys showed the most promising healing properties. Pinocembrin, which was revealed in BL1 (multifloral) and BL5 (orange) honey samples, is a flavanol that is already known to possess interesting biological activities, including healing. This study aims to investigate how a traditional food such as honey, which is appreciated for its nutritional value and used in folk medicine, can be enhanced as an effective modern remedial to promote a multifaceted and safe healing activity for all skin wounds.

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Honey, Wound Repair and Regenerative Medicine

Cited by 99 publications

References 38 publications

Honey-Mediated Wound Healing: H2O2 Entry through AQP3 Determines Extracellular Ca2+ Influx

Honey-Mediated Wound Healing: H2O2 Entry through AQP3 Determines Extracellular Ca2+ Influx

Prolotherapy: Potential for the Treatment of Chronic Wounds?

Evaluation of the In Vitro Wound-Healing Activity of Calabrian Honeys

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