Synthesis and characterization of zinc-silibinin complexes: A potential bioactive compound with angiogenic, and antibacterial activity for bone tissue engineering.

Zinc silibinin complex [Zn(sil)(HO)] and mixed ligand zinc complexes such as Zn(silibinin)(phenanthroline) [Zn(sil)(phen)], and Zn(silibinin)(neocuproine) [Zn(sil)(neo)] have been synthesized and characterized. The UV-vis spectra of the Zn(II) complexes showed a considerable shift in the intra-ligand transition. From the IR spectra, it is clear that carbonyl group in the C-ring is involved in the metal chelation besides A/C-ring hydroxyl group. Thermal gravimetric analysis showed that [Zn(sil)(neo)] has higher thermal stability compared to the other two Zn(II) complexes. The potential biological activities of the synthesized complexes were studied systematically. In osteoblast differentiation, silibinin and Zn-silibinin complexes enhanced osteoblast differentiation at the cellular level by increasing calcium deposition and ALP activity, and at molecular level increased osteoblast markers include Runx2, type 1 col, ALP and OC mRNAs expression. Additionally, Zn-silibinin complexes showed promising effects on osteoblast differentiation by regulating miR-590/Smad7 signaling pathway. Among the complexes, Zn(sil)(phen) showed more stimulatory effect on osteoblastic differentiation. These complexes also exhibited angiogenic property by increasing VEGF and Ang 1 expression in mouse MSCs and antibacterial activity against E. coli (Gram-negative) and S. aureus (Gram-positive) strains. Thus, the present study demonstrated that the Zn-silibinin complexes exhibit great potential as a pharmacological agent for bone tissue engineering.