Abstract

Skin is the outermost layer of the human body that is constantly exposed to environmental stressors, such as UV radiation and toxic chemicals, and is susceptible to mechanical wounding and injury. The ability of the skin to repair injuries is paramount for survival and it is disrupted in a spectrum of disorders leading to skin pathologies. Diabetic patients often suffer from chronic, impaired wound healing, which facilitate bacterial infections and necessitate amputation. Here, we studied the effects of gallic acid (GA, 3,4,5-trihydroxybenzoic acid; a plant-derived polyphenolic compound) on would healing in normal and hyperglucidic conditions, to mimic diabetes, in human keratinocytes and fibroblasts. Our study reveals that GA is a potential antioxidant that directly upregulates the expression of antioxidant genes. In addition, GA accelerated cell migration of keratinocytes and fibroblasts in both normal and hyperglucidic conditions. Further, GA treatment activated factors known to be hallmarks of wound healing, such as focal adhesion kinases (FAK), c-Jun N-terminal kinases (JNK), and extracellular signal-regulated kinases (Erk), underpinning the beneficial role of GA in wound repair. Therefore, our results demonstrate that GA might be a viable wound healing agent and a potential intervention to treat wounds resulting from metabolic complications.

Highlights

  • Gallic acid (GA) is a 3,4,5-trihydoxybenzoic acid, a phenolic acid found in almost all plants including fruits, leaves, and wild flowers [1,2], and has been reported to possess powerful health benefits, such as antioxidant, anti-inflammatory, analgesic, neuroprotective, anticancer, and anti-diabetic properties [3].The skin comprising of outer epidermis, underlying connective tissue, and dermis functions as a barrier that protects the body from environmental stressors, such as pathogens, excessive water loss, temperature, and physical stress [4]

  • We examined the effect of GA on Diabetes mellitus (DM)-induced delayed wound healing in both keratinocytes and fibroblasts using high glucose-containing medium to mimic diabetes

  • We found that GA has antioxidant properties, as well as cell migration effects in both normal and high glucose

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Summary

Introduction

Gallic acid (GA) is a 3,4,5-trihydoxybenzoic acid, a phenolic acid found in almost all plants including fruits, leaves, and wild flowers [1,2], and has been reported to possess powerful health benefits, such as antioxidant, anti-inflammatory, analgesic, neuroprotective, anticancer, and anti-diabetic properties [3]. Molecules 2016, 21, 899 damage to the epidermis and/or dermal layers, necessitating repair through a wound healing process comprised of four sequential phases; homeostasis, inflammation, proliferation/re-epithelialization, and maturation [5] When this well-ordered process is disrupted by factors, such as age, hyperglycemia, poor circulation, repeated trauma, continuous pressure, infections, or systemic illnesses, the wound fails to close in an expected time frame developing into a chronic wound [6]. Both acute and chronic wounds represent a major public healthcare burden affecting a relatively large population [7]. Impaired skin wound healing, leading to chronic ulcers, a common complication of DM [13]

Results
GA Protects
Antioxidant
GA Promotes Wound Healing Process in Hyperglucidic Condition
Effects
The Effects
Discussion
Cell Culture and Reagents
MTT Assay
Methylene Blue Staining
DPPH Free Radical Assay
In Vitro Wound Healing and Migration Assays
Western Blot Analysis
Quantitative Real-Time PCR
Cell Proliferation Assays
Full Text
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