Department of Morphology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-689, São Paulo, Brazil.
Sutton Research Laboratory, Kolling Institute of Medical Research, the University of Sydney at Royal North Shore Hospital, St Leonard, NSW 2065, Australia.
Molecules. 2018 Oct 30;23(11):2819. doi: 10.3390/molecules23112819.
Skin wound healing is a dynamic and complex process involving several mediators at the cellular and molecular levels. Lupeol, a phytoconstituent belonging to the triterpenes class, is found in several fruit plants and medicinal plants that have been the object of study in the treatment of various diseases, including skin wounds. Various medicinal properties of lupeol have been reported in the literature, including anti-inflammatory, antioxidant, anti-diabetic, and anti-mutagenic effects. We investigated the effects of lupeol (0.1, 1, 10, and 20 μg/mL) on in vitro wound healing assays and signaling mechanisms in human neonatal foreskin keratinocytes and fibroblasts. Results showed that, at high concentrations, Lupeol reduced cell proliferation of both keratinocytes and fibroblasts, but increased in vitro wound healing in keratinocytes and promoted the contraction of dermal fibroblasts in the collagen gel matrix. This triterpene positively regulated matrix metalloproteinase (MMP)-2 and inhibited the NF-κB expression in keratinocytes, suggesting an anti-inflammatory effect. Lupeol also modulated the expression of keratin 16 according to the concentration tested. Additionally, in keratinocytes, lupeol treatment resulted in the activation of Akt, p38, and Tie-2, which are signaling proteins involved in cell proliferation and migration, angiogenesis, and tissue repair. These findings suggest that lupeol has therapeutic potential for accelerating wound healing.
皮肤伤口愈合是一个涉及细胞和分子水平多种介质的动态而复杂的过程。羽扇豆醇是一种植物成分，属于三萜类，存在于几种水果植物和药用植物中，这些植物一直是治疗各种疾病的研究对象，包括皮肤伤口。文献中报道了羽扇豆醇具有多种药用特性，包括抗炎、抗氧化、抗糖尿病和抗诱变作用。我们研究了羽扇豆醇（0.1、1、10 和 20 μg/mL）对人新生儿包皮成纤维细胞和角质形成细胞体外伤口愈合试验和信号机制的影响。结果表明，在高浓度时，羽扇豆醇降低了角质形成细胞和成纤维细胞的增殖，但促进了体外角质形成细胞的伤口愈合，并促进了真皮成纤维细胞在胶原凝胶基质中的收缩。这种三萜类物质正向调节基质金属蛋白酶（MMP）-2 并抑制角质形成细胞中 NF-κB 的表达，提示具有抗炎作用。羽扇豆醇还根据测试的浓度调节角蛋白 16 的表达。此外，在角质形成细胞中，羽扇醇处理导致参与细胞增殖和迁移、血管生成和组织修复的 Akt、p38 和 Tie-2 信号蛋白的激活。这些发现表明，羽扇豆醇具有加速伤口愈合的治疗潜力。
