Wound healing efficacy of Jamun honey in diabetic mice model through reepithelialization, collagen deposition and angiogenesis

Abstract

Diabetic patients are frequently afflicted with impaired wound healing where linear progression of molecular and cellular events compromised. Despite of meaningful progress in diabetic treatment, management of diabetic chronic wounds is still challenging. Jamun ( Syzygium cumini ) honey may be a promising candidate for diabetic wound healing and need to explore in detail. So present study was designed to evaluate the efficacy of Jamun honey (JH) for diabetic wound healing in in vitro wound (primary fibroblasts) model and in in vivo of diabetic mice (Streptozotocin induced) model. The fibroblast cell model was studied for migratory behaviour and myofibrolasts infiltration under honey interventions via scratch/migration assay, immuno-cytochemistry and western blot. We applied FDA approved Manuka honey (MH) as positive control and JH as test honey to evaluate wound re-epithelialization, sub-epithelial connective tissue modification and angiogenesis via histo-pathological and immuno-histochemical analysis. JH (0.1% v/v) dilution has notably improved wound closure, migration with concomitant α-SMA expressions in vitro . Topical application of JH in diabetic mice model showed significant (*p ≤ 0.05) wound closure, reepithelialization, collagen deposition (I/III) and balanced the myofibroblasts formation. It also modulated vital angiogenic markers ( viz HIF-1α, VEGF, VEGF R–II) significantly (*p ≤ 0.05). All these observations depicted that JH promotes sequential stages of wound healing in diabetic mice model. The results of the present study established Jamun honey as good as Manuka honey considering wound closure, re-epithelialization, collagen deposition and pro-angiogenic potential.

Role of Honey in Advanced Wound Care

“…This dynamic process is strongly regulated by signals from serum and the surrounding extracellular matrix environment [ 67 ]. Stimulation of angiogenesis by honey was demonstrated in an in vitro study with analogues of angiogenesis and an endothelial proliferation assay [ 68 ], and more recently, in another in vivo-model study [ 69 ].…”

Therapeutic Properties of Honey for the Management of Wounds; Is There a Role in the Armamentarium of Diabetic Foot Ulcer Treatment? Results From In vitro and In vivo Studies

“…85 In another study, researchers isolated primary fibroblasts from diabetic and nondiabetic animals, created scratch wounds, and examined their migratory behavior when treated with jamun honey and manuka honey. 86 Interestingly, nondiabetic mice-derived fibroblasts exhibited an increased wound closure rate under both types of honey dilutions in comparison with the untreated fibroblasts, but this was not the case for fibroblasts derived from diabetic mice. However, cell migration was increased for fibroblasts derived from diabetic and nondiabetic animals after treatment with jamun and manuka honey when compared to untreated cells.…”

“…Moreover, honey-treated fibroblasts derived from both diabetic and nondiabetic mice exhibited an up-regulation of alpha-smooth muscle actin expression, which is a marker of prime myofibroblasts and of collagens I and III. 86 In another in vitro study, researchers used a human fibroblast cell line and examined the wound healing effects of acacia, buckwheat, and manuka honey after creating wounds with the scratch assay. 87 Cells exposed to all 3 types of honey showed higher wound closure rates when compared to untreated cells, while the number of migrating cells was also higher in the presence of all types of honey.…”

Diabetic wound healing: The impact of diabetes on myofibroblast activity and its potential therapeutic treatments

“…The study concluded that Jamun had similar efficacy to the already approved Manuka honey. 88 With additional testing, this has the potential to rapidly accelerate the wound repair process.…”