Department of Biochemistry, Pharmacology and Physiology, Federal University of Triangulo Mineiro (UFTM), Uberaba, Minas Gerais, Brazil.
São Paulo State University (UNESP), Botucatu Medical School, Botucatu, São Paulo 18.618-687, Brazil; National Heart and Lung Institute, Imperial College London, London, UK; Bioengineering & Biomaterials Group, São Paulo State University (UNESP), School of Pharmaceutical Sciences, Km 01 Araraquara-Jaú Road, Araraquara, São Paulo, Brazil; Science Faculty, São Paulo State University (UNESP), Bauru, São Paulo 17033-360, Brazil.
Biomater Adv. 2024 Feb;157:213754. doi: 10.1016/j.bioadv.2023.213754. Epub 2023 Dec 28.
Chronic wounds pose significant health concerns. Current treatment options include natural compounds like natural rubber latex (NRL) from Hevea brasiliensis. NRL, particularly the F1 protein fraction, has demonstrated bioactivity, biocompatibility, and angiogenic effects. So far, there is no study comparing F1 protein with total NRL serum, and the necessity of downstream processing remains unknown. Here, we evaluated the angiogenic potential of F1 protein compared to total NRL serum and the need for downstream processing. For that, ion exchange chromatography (DEAE-Sepharose), antioxidant activity, physicochemical characterization, cell culture in McCoy fibroblasts, and wound healing in Balb-C mice were performed. Also, the evaluation of histology and collagen content and the levels of inflammatory mediators were quantified. McCoy fibroblast cell assay showed that F1 protein (0.01 %) and total NRL serum (0.01 %) significantly increased cell proliferation by 47.1 ± 11.3 % and 25.5 ± 2.5 %, respectively. However, the AA of F1 protein (78.9 ± 0.8 %) did not show a significant difference compared to NRL serum (77.0 ± 1.1 %). F1 protein and NRL serum were more effective in wound management in rodents. Histopathological analysis confirmed accelerated healing and advanced tissue repair. Similarly, the F1 protein (0.01 %) increased collagen, showing that this fraction can stimulate the synthesis of collagen by fibroblastic cells. Regarding cytokines production (IL-10, TNF-α, IFN-γ), F1 protein and NRL serum did not exert an impact on the synthesis of these cytokines. Furthermore, we did not observe statistically significant changes in dosages of enzymes (MPO and EPO) among the groups. Nevertheless, Nitric Oxide dosage was reduced drastically when the F1 protein (0.01 %) protein was applied topically. These findings contribute to the understanding of F1 protein and NRL serum properties and provide insights into cost-effectiveness and practical applications in medicine and biotechnology. Therefore, further research is needed to assess the economic feasibility of downstream processing for NRL-based herbal medicine derived from Hevea brasiliensis.
慢性伤口是一个严重的健康问题。目前的治疗选择包括天然化合物，如来自 Hevea brasiliensis 的天然橡胶乳胶 (NRL)。NRL，特别是 F1 蛋白部分，已显示出生物活性、生物相容性和血管生成作用。到目前为止，还没有研究比较 F1 蛋白与总 NRL 血清，也不知道是否需要下游处理。在这里，我们评估了 F1 蛋白与总 NRL 血清相比的血管生成潜力，以及是否需要下游处理。为此，我们进行了离子交换层析（DEAE-Sepharose）、抗氧化活性、理化特性、McCoy 成纤维细胞培养和 Balb-C 小鼠伤口愈合实验。此外，还对组织学和胶原蛋白含量以及炎症介质水平进行了定量评估。McCoy 成纤维细胞细胞实验表明，F1 蛋白（0.01%）和总 NRL 血清（0.01%）分别显著增加细胞增殖 47.1%±11.3%和 25.5%±2.5%。然而，F1 蛋白的 AA（78.9%±0.8%）与 NRL 血清（77.0%±1.1%）相比没有显著差异。F1 蛋白和 NRL 血清在啮齿动物的伤口管理中更有效。组织病理学分析证实了加速愈合和组织修复的进展。同样，F1 蛋白（0.01%）增加了胶原蛋白的含量，表明该部分可以刺激成纤维细胞合成胶原蛋白。关于细胞因子的产生（IL-10、TNF-α、IFN-γ），F1 蛋白和 NRL 血清对这些细胞因子的合成没有影响。此外，我们没有观察到各组间酶（MPO 和 EPO）剂量有统计学意义的变化。然而，当局部应用 F1 蛋白（0.01%）时，NO 剂量大大降低。这些发现有助于了解 F1 蛋白和 NRL 血清的特性，并为成本效益和医学和生物技术中的实际应用提供了深入的见解。因此，需要进一步研究来评估基于 Hevea brasiliensis 的 NRL 草药的下游处理的经济可行性。
