Sá Ana Flor, Diniz Ivana Márcia Alves, Oliveira Renata Barbosa de, Diniz Marina Gonçalves, Cortés Maria Esperanza, Souza Letícia Lopes de, Olórtegui Carlos Delfin Chávez, Lages Frederico Santos
Universidade Federal de Minas Gerais - UFMG, School of Dentistry, Department of Restorative Dentistry, Belo Horizonte, MG, Brazil.
Universidade Federal de Minas Gerais - UFMG, School of Pharmacy, Department of Pharmaceutical Products, Belo Horizonte, MG, Brazil.
Braz Oral Res. 2024 Dec 9;38:e123. doi: 10.1590/1807-3107bor-2024.vol38.0123. eCollection 2024.
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.
姜黄素存在于姜黄根茎（姜黄属植物姜黄）中，因其潜在的健康益处，包括抗炎、抗氧化和伤口愈合特性，已得到广泛研究。然而，由于其生物利用度低和药代动力学不理想，人们已开发出类似化合物以获得更好的生物制药特性和增强的生物学效应。在本研究中，我们评估了姜黄素及其三种合成类似物（DMAD、DMAM和RI75）对前成骨细胞系（MC3T3-E1）的活力和分化的影响。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）、基质细胞衍生因子1（SDF-1/CXCL12）和 runt相关转录因子2（Runx2）。细胞用浓度为10、30或50μM的姜黄素和三种类似物处理。在24、48和72小时后，与所有浓度下标准条件处理的细胞相比，所有测试的类似物和姜黄素均表现出中度至无细胞毒性。只有RI75类似物显示出组织再生关键因子SDF-1的上调。与姜黄素相比，DMAM和RI75类似物也上调了与骨分化相关的Runx2和VEGF。RI75类似物比姜黄素表现出更大的矿化作用，并且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，50μM的姜黄素类似物RI75与天然姜黄素相比具有相似的毒性，但具有增强的生物学活性，使其成为材料生物改性的有前途的物质。
