The role of hesperidin on healing an incised wound in an experimentally induced diabetic adult male albino rats. Histological and Immunohistochemical Study

Abstract

Background: Skin ulcers and poor healing are serious problems in diabetic patients. Products of citrus herbal are promising in new studies. Many benefits of hesperidin especially for cutaneous functions including skin healing have been demonstrated. Aim of the Study: The aim of this work was to evaluate the possible healing effect of hesperidin on diabetic skin injury in adult male albino rats. Materials and Methods: Forty adult male albino rats were randomly divided into four equal groups (10 rats, each). Group I: the control; group II: hesperidin; group III: untreated diabetic rats; and group IV, diabetic rats treated with hesperidin. Skin specimens were obtained and processed for histological study using Hematoxylin and Eosin (H & E), Mallory trichrome (M.T) and immunohistochemical study using vascular endothelial growth factor (VEGF) Electron microscopic examination was done. Morphometric measurements of epidermal thickness and area percentage of collagen fibers were carried out followed by statistical analysis. Results: The untreated diabetic group showed incomplete closure and scab covering proliferating epidermis. Another area of self-healed malformed skin revealed reepithelization with increased thickness of epidermis significantly. Epidermal cells showed loss of polarity and in between hyaline material. The underlying dermis revealed a significantly increased disorganized collagen fibers and massive inflammatory cells infiltration. Also, moderate VEGF immunoexpression was observed. Diabetic skin treated with hesperidin revealed complete closure of the wounds with thin apparently normal epidermis. The underlying dermis revealed normal amount of well-organized collagen fibers with few inflammatory cells infiltration and spaces between collagen fibers. Strong positive VEGF immunoexpression was observed reflecting enhanced angiogenesis. Conclusion: Diabetic skin injuries are healing badly in relatively prolonged time. Hesperidin can be used as an adjunctive or alternative agent in diabetic wound giving good cosmetic results.

Citrus Flavonoids: Biological Activities, Implementation in Skin Health, and Topical Applications: A Review

“…61 Induction of VEGF expression and angiogenesis has also been reported in hesperidin-treated skin lesions in diabetic rats, causing complete wound closure and growth of a normal epidermis: overall a good cosmetic outcome. 62 On the other hand, its topical application has been proved to accelerate and improve the healing of normal and irradiated wounds. This is attributed to the strong free radical scavenging activity.…”

“…Furthermore, hesperidin has shown therapeutic effects on chronic diabetic foot ulcers by stimulating angiogenesis and vasculogenesis, which is induced by upregulation of VEGF-c, Ang-1/Tie-2, and TGF-β/Smad-2/3 . Induction of VEGF expression and angiogenesis has also been reported in hesperidin-treated skin lesions in diabetic rats, causing complete wound closure and growth of a normal epidermis: overall a good cosmetic outcome . On the other hand, its topical application has been proved to accelerate and improve the healing of normal and irradiated wounds.…”

Bioactive Phytochemicals of Citrus reticulata Seeds—An Example of Waste Product Rich in Healthy Skin Promoting Agents

“…Hesperidin has sufficient healing benefits on injured skin. Hesperidin can thus be utilized as a supplement or alternative to other wound-healing agents [50][51][52]. Aside from flavonoids, fatty acid esters of glycerol [53,54], acrylic acid derivatives [55], and sterols [56] all had similar wound healing effects.…”

Hesperidin - loaded PVA/alginate hydrogel: targeting NFκB/iNOS/COX-2/TNF-α inflammatory signaling pathway

“…Furthermore, macrophages also secrete growth factors, chemokines, and cytokines, which subsequently induce the migration and proliferation of keratinocytes, fibroblasts, and endothelial cells ( 8 ). Additionally, macrophages contribute to the process of angiogenesis and play a role in the formation of vascularized connective tissue, ultimately resulting in the closure of the wound ( 9 ). The remodeling phase commences in the proliferation stage and extends over an extended duration.…”

“…The remodeling phase commences in the proliferation stage and extends over an extended duration. In this stage, the body engages in both collagen production and its breakdown, ensuring a delicate equilibrium between the requirement for tensile strength and the remodeling of new tissue ( 9 ). Hence, owing to their inherent physical attributes, including swelling and biodegradability, hydrogels encompass many of the sought-after qualities of an ideal wound dressing ( 6 , 10 ).…”