Binary curcuminoid complex CRE-Bin inhibits osteoclast differentiation by suppressing the canonical NF-κB signaling pathway and modulating microRNA-223 expression.

Curcuminoids, the major bioactive compounds in Curcuma longa L., inhibit osteoclast differentiation-a key process in bone resorption. microRNA-223 regulates osteoclast differentiation by targeting nuclear factor I-A. How curcuminoids influence osteoclast differentiation through microRNA-223 is unclear. This study investigated the effects of CRE-Bin-a binary curcuminoid complex of a curcuminoid-rich extract and hydroxypropyl-β-cyclodextrin-on osteoclast differentiation. In murine receptor activator of nuclear factor-κB ligand-stimulated RAW 264.7 macrophages, CRE-Bin inhibited osteoclast differentiation and bone resorption by reducing tartrate-resistant acid phosphatase activity, cathepsin K expression, reactive oxygen species production, and canonical NF-κB signaling pathway. CRE-Bin suppressed microRNA-223 expression at the primary, precursor, and mature stages while upregulating nuclear factor I-A expression, suggesting dual regulatory effects. Molecular docking simulations demonstrated strong interactions between microRNA-223 and the IκBα/p50/p65 complex, indicating crosstalk between microRNA-223 and canonical NF-κB signaling pathway. Binding affinity predictions revealed moderate interactions between curcuminoids and mature microRNA-223, underscoring their potential for microRNA-targeted modulation. These findings position CRE-Bin as a promising multitarget therapeutic agent for bone-related disorders and diseases, warranting experimental and computational investigations.