Lupeol, a Dietary Triterpene, Enhances Wound Healing in Streptozotocin-Induced Hyperglycemic Rats with Modulatory Effects on Inflammation, Oxidative Stress, and Angiogenesis

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.

From Inflammation to Cutaneous Repair: Topical Application of Lupeol Improves Skin Wound Healing in Rats by Modulating the Cytokine Levels, NF-κB, Ki-67, Growth Factor Expression, and Distribution of Collagen Fibers

“…Our results showed an increase in the gene expression of TGF-β1 in the lupeol-treated group after seven days corresponding to the proliferative phase, which mediates the formation of granulation tissue and local neovascularization. These data corroborate our previous study, where there was an increase in the expression of TGF-β in the lupeol-treated group in diabetic rat wounds [13].…”

“…Some studies have demonstrated that lupeol is associated with the modulation of various inflammatory agents, such as TNF-α, IL-1β, and IL-6 [26]. Recently, we have shown that lupeol treatment of hyperglycemic rat wounds was able to favorably regulate cytokine levels, to provide a net anti-inflammatory effect [13]. The present study confirms this potential anti-inflammatory effect of lupeol in cutaneous lesions of rats by significantly reducing the levels of proinflammatory cytokines such as TNF-α and IL-6 after 3 and 14 days of treatment and increasing the IL-10 levels after 7 and 14 days of treatment.…”

“…Based on this work, a recent study developed by our group demonstrated an important role for lupeol on hyperglycemia-induced impaired wound healing after 14 days of treatment. The results revealed a significant decrease in the inflammatory process, better formation of granulation tissue, and increased vascularization and deposition of collagen fibers after lupeol treatment [13]. However, the effectiveness of lupeol on skin wound healing after different treatment periods has not been investigated, and its underlying mechanisms in normoglycemic rats remain unknown.…”

LPS-stimulated Macrophage Exosomes Inhibit Inflammation by Activating the Nrf2 / HO-1 Defense Pathway and Promote Wound Healing in Diabetic Rats

“…In this experiment, we found that lipopolysaccharide stimulated exosomes secreted by macrophages (LPS-Exos) can promote the healing of diabetic rats' skin wounds, and further veri ed that LPS-Exos can inhibit the in ammation and oxidative stress of diabetic rats' skin wounds through in vitro and in vivo experiments.Chronic in ammation and oxidative stress play an important role in the pathogenesis of diabetes mellitus [27]. Previous studies have shown that exosomes do have a protective effect on skin defects in diabetic rats [28,29].At the same time, our experimental team found that LPS-Exos had superior anti-in ammatory effect in the disease of cerebral ischemia-reperfusion [11].Therefore, we speculate whether LPS-Exos has a better inhibitory effect on chronic in ammation and oxidative stress of diabetic skin wounds.Fortunately, we have proved through a series of experiments in vivo and in vitro that LPS-Exos can inhibit in ammation and accelerate wound healing in diabetic rats by activating Nrf2 / HO-1 pathway.…”

Lupeol, a Plant-Derived Triterpenoid, Protects Mice Brains against Aβ-Induced Oxidative Stress and Neurodegeneration

“…Lupeol is a pentacyclic triterpenoid and biologically active compound, naturally found in fruits, vegetables, and several medicinal plants [ 22 ]. In vegetables, it is mainly found in white cabbage, pepper, cucumber, and tomato, and in fruits, it is mainly found in mango, fig, strawberry, and red grapes [ 23 ].…”