Abstract
Skin wound healing is a highly complex event that involves different mediators at the cellular and molecular level. Lupeol has been reported to possess different biological activities, such as anti-inflammatory, antioxidant, antidiabetic, and in vitro wound healing properties, which motivated us to proceed with in vivo studies. We aimed to investigate the wound healing effect of lupeol-based cream for 3, 7, and 14 days. Wound excisions were induced on the thoraco-lumbar region of rats and topically treated immediately after injury induction. Macroscopic, histopathological, and immunohistochemical analyses were performed. Cytokine levels were measured by ELISA and gene expression was evaluated by real-time RT-qPCR. Our results showed a strong wound-healing effect of lupeol-based cream after 7 and 14 days. Lupeol treatment caused a reduction in proinflammatory cytokines (TNF-a, IL-1β, and IL-6) and gene and protein NF-κB expression, and positively altered IL-10 levels, showing anti-inflammatory effects in the three treatment periods. Lupeol treatment showed involvement in the proliferative phase by stimulating the formation of new blood vessels, increasing the immunostaining of Ki-67 and gene expression, and immunolabeling of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), and increasing gene expression of transforming growth factor beta-1 (TGF-β1) after seven days of treatment. Lupeol was also involved in the tissue regeneration phase by increasing the synthesis of collagen fibers noted in the three treatment periods analyzed. Our findings suggest that lupeol may serve as a novel therapeutic option to treat cutaneous wounds by regulating mechanisms involved in the inflammatory, proliferative, and tissue-remodeling phases.
Highlights
Wound healing is a fascinating but complicated process, affected by several factors that contribute jointly to wound closure, including blood coagulation, inflammation, fibroplasia, collagen deposition, and wound contraction [1]
Our results showed increased gene expression of epidermal growth factor (EGF) in the lupeol-based cream treatment, as well as increased immunostaining for this growth factor after 7 and 14 of treatments analyzed in the border and lesion center, and that way, confirming the role of the lupeol on re-epithelialization in the healing process
The data obtained in our study showed an increase in the number of blood vessels in the border and lesion center in the lupeol-treated groups after 7 and 14 days, together with an increase in gene expression observed after 3 and 7 days of treatment and in the immunolabeling of vascular endothelial growth factor (VEGF) during the three treatment periods tested
Summary
Wound healing is a fascinating but complicated process, affected by several factors that contribute jointly to wound closure, including blood coagulation, inflammation, fibroplasia, collagen deposition, and wound contraction [1]. The success of skin restructuring is dependent on a cascade of ordered events involving cellular, biochemical, and molecular responses and/or interactions. For didactic reason, this process is analyzed from three overlapping phases: inflammatory phase, formed by events such as hemostasis and inflammation; proliferative phase, characterized by granulation tissue formation, angiogenesis, and re-epithelialization; and the remodeling phase of the extracellular matrix [2]. Secondary metabolites or active compounds isolated from many natural sources, in addition to plants, have been shown to be responsible for the induction of skin wound healing in animal models [5]
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