In Vitro and In Silico Analyses of Biomolecular Regulation of Liposomal CRE-SD on Osteoclastogenesis via a Canonical NF-κB Signaling Pathway

Abstract

Curcuminoids, namely curcumin, demethoxycurcumin, and bisdemethoxycurcumin, are the major active compounds found in Curcuma longa L. (turmeric). Although their suppressive effects on bone resorption have been demonstrated, their pharmacokinetic disadvantages remain a concern. Herein, solid dispersion of a curcuminoid-rich extract (CRE), comprising such curcuminoids, was utilized to prepare CRE-SD; subsequently, liposome encapsulation of the CRE-SD was performed to yield liposomal CRE-SD. In vitro release assessment revealed that a lower cumulative mass percentage of CRE-SD was released from liposomal CRE-SD than from CRE-SD samples. After culture of murine RANKL-stimulated RAW 264.7 macrophages, in vitro examinations confirmed that liposomal CRE-SD may impede osteoclastogenesis by suppressing p65 and IκBα phosphorylation, together with nuclear translocation and transcriptional activity of phosphorylated p65. Blind docking simulations showed the high binding affinity between curcuminoids and the IκBα/p50/p65 protein complex, along with many intermolecular interactions, which corroborated the in vitro findings. Therefore, liposomal CRE-SD can inhibit osteoclastogenesis via the canonical NF-κB signaling pathway, suggesting its pharmacological potential for treating bone diseases with excessive osteoclastogenesis.