Chemical Biology and Nanobiotechnology Laboratory, AU-KBC Research Centre, Anna University, MIT Campus, Chromepet, Chennai, 600 044, India.
Centre for Biotechnology, Anna University, Chennai, Tamil Nadu, 600 025, India.
J Biol Inorg Chem. 2018 Jul;23(5):753-762. doi: 10.1007/s00775-018-1566-4. Epub 2018 May 19.
In the recent decades, flavonoid metal complexes have been widely investigated for their multifaceted role in enabling osteoblast differentiation and bone formation. Silibinin complexed with copper(II) ion has been synthesized along with two mixed ligand complexes, namely copper(II) silibinin-phenanthroline and neocuproine as co-ligands, and their positive role in promoting neovacularization and osteoblast differentiation was investigated. Silibinin mono complex [Cu(sil)(HO)] and [Cu(sil)(phen)] showed similar UV-visible absorption in the region of 315 and 222 nm, whereas Cu(silibinin)(neocuproine) [Cu(sil)(neo)] showed a blueshift in the 320 nm transition. The involvement of carbonyl group present in the C-ring in metal ion chelation was identified by FT-IR analysis. Thermal gravimetric analysis (TGA) depicted that [Cu(sil)(neo)] has higher thermal stability when compared with the control silibinin and Cu-silibinin mono, and phen complexes. Cu-silibinin complexes were found to be non-toxic to human MG-63 cells and mouse mesenchymal stem cells (MSCs). Our investigations identified the positive role of these complexes in promoting osteoblast differentiation by enhancing calcium deposition and alkaline phosphatase (ALP) activity at the cellular level and stimulation of osteoblastic marker genes such as Runx2, ALP, type 1 collagen, and OCN mRNAs expression at the molecular level. These complexes also supported angiogenesis by upregulation of VEGF and Ang 1 expression in mouse MSCs. Hence, our results suggest that the potential of these metal complexes along with mixed ligand complexes promoted osteoblast differentiation, thus warranting its candidature for bone tissue regeneration application.
在最近几十年中，黄酮类金属配合物因其在促进成骨细胞分化和骨形成方面的多方面作用而受到广泛研究。已经合成了与铜（II）离子配位的水飞蓟素配合物，以及两种混合配体配合物，即铜（II）水飞蓟素-菲咯啉和新铜试剂作为共配体，并研究了它们在促进新血管生成和成骨细胞分化中的积极作用。水飞蓟素单核配合物[Cu(sil)(HO)]和[Cu(sil)(phen)]在 315 和 222nm 区域显示出相似的紫外-可见吸收，而 Cu(silibinin)(neocuproine)[Cu(sil)(neo)]在 320nm 跃迁中显示出蓝移。FT-IR 分析确定了 C 环中羰基的存在参与了金属离子螯合。热重分析（TGA）表明，与对照水飞蓟素和 Cu-水飞蓟素单核、苯并配合物相比，[Cu(sil)(neo)]具有更高的热稳定性。Cu-水飞蓟素配合物被发现对人 MG-63 细胞和小鼠间充质干细胞（MSCs）没有毒性。我们的研究表明，这些配合物通过增强细胞水平的钙沉积和碱性磷酸酶（ALP）活性以及刺激成骨细胞标记基因如 Runx2、ALP、I 型胶原和 OCN mRNAs 的表达，在分子水平上促进成骨细胞分化。这些配合物还通过上调小鼠 MSCs 中 VEGF 和 Ang 1 的表达来支持血管生成。因此，我们的结果表明，这些金属配合物以及混合配体配合物的潜力促进了成骨细胞分化，因此有资格用于骨组织再生应用。
