Mixed-ligand copper(II) complex of quercetin regulate osteogenesis and angiogenesis

• Published in: Materials Science & Engineering C 2018-02, Vol.83, p.187-194
• Main Authors: Vimalraj, Selvaraj, Rajalakshmi, Subramaniyam, Raj Preeth, Desingh, Vinoth Kumar, Sivasubramanian, Deepak, Thirumalai, Gopinath, Venkatraman, Murugan, Kadarkarai, Chatterjee, Suvro
• Format: Article
• Language: English
• Subjects: Alkaline phosphatase; Angiogenesis; Biocompatibility; Biomedical materials; Blood vessels; Calcium; Cbfa-1 protein; Cell Differentiation - drug effects; Chelation; Collagen; Coordination compounds; Copper; Copper - chemistry; Copper - pharmacology; Copper compounds; Cu(II) complexes; Differentiation; Fourier transforms; Gene expression; Ligands; Materials science; microRNA; MicroRNAs - genetics; miRNA; Orthopedics; Osteoblast differentiation; Osteoblastogenesis; Osteoblasts - cytology; Osteoblasts - drug effects; Osteogenesis; Osteogenesis - drug effects; Pharmacology; Quercetin; Quercetin - chemistry; Quercetin - pharmacology; Ribonucleic acid; RNA; Studies; Ultraviolet radiation
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2017.09.005

Copper(II) complex of quercetin Cu+Q, mixed ligand complexes, quercetin-Cu(II)-phenanthroline [Cu+Q(PHt)] and quercetin-Cu(II)-neocuproine [Cu+Q(Neo)] have been synthesized and characterized. From the FT-IR spectroscopic studies, it was evident that C-ring of quercetin is involved in the metal chelation in all the three copper complexes. C-ring chelation was further proven by UV–Visible spectra and the presence of Cu(II) from EPR spectroscopic investigations. These complexes were found to have osteogenic and angiogenic properties, observed through in vitro osteoblast differentiation and chick embryo angiogenesis assay. In osteoblast differentiation, quercetin-Cu(II) complexes treatment increased calcium deposition and alkaline phosphatase activity (ALP) activity at the cellular level and stimulated Runx2 mRNA and protein, ALP mRNA and type 1 collagen mRNA expression at the molecular level. Among the complexes, Q+Cu(PHt) showed more effects on osteoblast differentiation when compared to that of other two copper complexes. Additionally, Q+Cu(Neo) showed more effect compared to Q+Cu. Furthermore, the effect of these complexes on osteoblast differentiation was confirmed by the expression of osteoblast specific microRNA, pre-mir-15b. The chick embryo angiogenesis assay showed that angiogenic parameters such as blood vessel length, size and junctions were stimulated by these complexes. Thus, the present study demonstrated that quercetin copper(II) complexes exhibit as a pharmacological agent for the orthopedic application. [Display omitted] •Copper(II) complex of quercetin and mixed ligand complexes have been synthesized.•Cu(II) chelates with the C-ring of quercetin was studied by UV-Visible and IR spectroscopy.•Cu+Q(PHt) where phenanthroline co-ligand complex showed the improved osteoblast differentiation.•Copper(II) complexes increased osteoblast specific miRNA expression.•Copper(II) complexes also exhibited angiogenic potency.