Ana Flor Sá, Ivana Márcia Alves Diniz, Renata Barbosa de Oliveira, Marina Gonçalves Diniz, Maria Esperanza Cortés, Letícia Lopes de Souza, Carlos Delfin Chávez Olórtegui, Frederico Santos Lages
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We also assessed the expression of key genes involved in tissue regeneration: vascular endothelial growth factor (vegf), stromal-derived growth factor 1 (SDF-1/CXCL12), and runt-related transcription factor 2 (runx2). The cells were treated with curcumin and the three analogues at concentrations of 10, 30, or 50 μM. All tested analogues and curcumin exhibited moderate to no cell toxicity compared to the cells treated under standard conditions across all concentrations after 24, 48, and 72 hours. Only the RI75 analogue showed upregulation of SDF-1, a crucial factor in tissue regeneration. Compared to curcumin, the DMAM and RI75 analogues also upregulated runx2 and vegf, both associated with osteodifferentiation. The RI75 analogue demonstrated greater mineralization than curcumin, and both promoted more nodule formation than the untreated control. 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引用次数: 0
摘要
姜黄素,发现于姜黄根茎(Curcuma longa L.)中,因其潜在的健康益处而被广泛研究,包括抗炎、抗氧化和伤口愈合特性。然而,由于其低生物利用度和不利的药代动力学,类似的化合物已经被开发出来,以获得更好的生物制药特性和增强的生物效应。在这项研究中,我们评估了姜黄素及其三种合成类似物(DMAD, dam和RI75)对成骨前细胞系(MC3T3-E1)的活力和分化的活性。我们还评估了参与组织再生的关键基因的表达:血管内皮生长因子(vegf)、基质衍生生长因子1 (SDF-1/CXCL12)和矮子相关转录因子2 (runx2)。姜黄素和三种类似物分别以10、30和50 μM的浓度处理细胞。与在标准条件下处理的细胞相比,所有测试的类似物和姜黄素在24、48和72小时后均表现出中度至无细胞毒性。只有RI75类似物显示了组织再生的关键因子SDF-1的上调。与姜黄素相比,ddam和RI75类似物也上调runx2和vegf,两者都与骨分化有关。RI75类似物比姜黄素表现出更大的矿化,两者都比未处理的对照促进了更多的结节形成。我们的数据表明,姜黄素类似物RI75在50 μM下具有与天然姜黄素相似的毒性,但具有更高的生物活性,使其成为一种有前景的材料生物修饰物质。
Effect of curcumin and three analogues on pre-osteoblast cells' viability, differentiation, and gene expression.
Curcumin, found in turmeric rhizomes (Curcuma longa L.), has been widely studied for its potential health benefits, including anti-inflammatory, antioxidant, and wound-healing properties. However, due to its low bioavailability and unfavorable pharmacokinetics, analogous compounds have been developed to obtain better biopharmaceutical characteristics and enhanced biological effects. In this study, we evaluated the activity of curcumin and three of its synthetic analogues (DMAD, DMAM, and RI75) on the viability and differentiation of a pre-osteoblastic cell line (MC3T3-E1). We also assessed the expression of key genes involved in tissue regeneration: vascular endothelial growth factor (vegf), stromal-derived growth factor 1 (SDF-1/CXCL12), and runt-related transcription factor 2 (runx2). The cells were treated with curcumin and the three analogues at concentrations of 10, 30, or 50 μM. All tested analogues and curcumin exhibited moderate to no cell toxicity compared to the cells treated under standard conditions across all concentrations after 24, 48, and 72 hours. Only the RI75 analogue showed upregulation of SDF-1, a crucial factor in tissue regeneration. Compared to curcumin, the DMAM and RI75 analogues also upregulated runx2 and vegf, both associated with osteodifferentiation. The RI75 analogue demonstrated greater mineralization than curcumin, and both promoted more nodule formation than the untreated control. Our data suggest that the curcumin analogue RI75 at 50 μM presents similar toxicity but enhanced biological activity compared to natural curcumin, making it a promising substance for material biomodifications.