Abstract
Impaired wound healing is a debilitating complication of diabetes that leads to significant morbidity, particularly foot ulcers. Natural products have shown to be effective in treating skin wounds. Lupeol is known to stimulate angiogenesis, fibroblast proliferation, and expressions of cytokines and growth factors involved in wound healing. The study is performed to evaluate the wound healing activity of lupeol in streptozotocin-induced hyperglycemic rats by macroscopical, histological, immunohistochemical, immunoenzymatic, and molecular methods. Percentage of wound closure and contraction was increased in the lupeol-treated group when compared to the Lanette group. Histopathological observation revealed decreased inflammatory cell infiltration and increased proliferation of fibroblasts, vascularization, and deposition of collagen fibers after lupeol treatment. Immunohistochemical analyses showed decreased intensity of NF-κB and increased intensity of FGF-2, TGF-β1, and collagen III. ELISA results revealed downregulated IL-6 levels and upregulated IL-10 levels in response to lupeol. The mRNA expression levels of Hif-1α, Sod-2, and Ho-1 were significantly increased in response to lupeol as compared to Lanette whereas Nf-κb and Vegf-A levels were decreased in relation to insulin and lupeol treatment. These findings indicate that lupeol possesses wound healing potential in hyperglycemic conditions and may be useful as a treatment for chronic wounds in diabetic patients.
Highlights
Diabetes mellitus (DM) is a chronic metabolic disease, which is characterized by elevated levels of blood glucose leading, over time, to heart, blood vessel, eye, kidney, and nerve damage and failure to repair damage in skin wounds [1].According to the World Health Organization (WHO), this disease affects 171 million people worldwide, and this number may be projected to reach approximately 366 million by 2030 [2]
We investigated whether lupeol enhances wound healing in streptozotocin-induced hyperglycemic rats via reduction of the inflammatory process and an increase in markers involved in oxidative stress, angiogenesis, formation of granulation tissue, and extracellular matrix remodelling
All rats used in the present study showed the characteristic signs of hyperglycemia from the second day after the administration of STZ
Summary
Diabetes mellitus (DM) is a chronic metabolic disease, which is characterized by elevated levels of blood glucose leading, over time, to heart, blood vessel, eye, kidney, and nerve damage and failure to repair damage in skin wounds [1].According to the World Health Organization (WHO), this disease affects 171 million people worldwide, and this number may be projected to reach approximately 366 million by 2030 [2]. The increased production of free radicals and decreased antioxidant activities of enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GPx), heme oxygenase-1, (HO-1) and heme oxygenase-2 (HO-2), may aggravate the situation leading to a delay in diabetic wound healing. Growth factors such as epidermal growth factor (EGF), fibroblast growth factor (FGF), transforming growth factor-beta (TGF-β1), and vascular endothelial growth factor (VEGF) and several molecules including hypoxia-inducible factor-1alpha (HIF-1α) are involved in the healing process by stimulating and activating cell proliferation via activation of various reactions, such as angiogenesis, reepithelialization, and differentiation and production of the extracellular matrix [11, 12]. We investigated the role of the mediators involved in the healing process in hyperglycemic rat wounds
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