Modified Curcuminoid-Rich Extract Liposomal CRE-SDInhibits Osteoclastogenesis via the 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, we utilized solid dispersion of a curcuminoid-rich extract (CRE), comprising such curcuminoids, to prepare CRE-SD; subsequently, we performed liposome encapsulation of the CRE-SD 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, our 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 our 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.

Curcumin in Cancer and Inflammation: An In-Depth Exploration of Molecular Interactions, Therapeutic Potentials, and the Role in Disease Management

“…Additionally, research led by Sompot Jantarawong explored the detailed interactions between curcumin and the p50 subunit of NF-κB [ 108 ]. Their findings revealed a variety of interaction types, including both classical and non-classical hydrogen bonds, such as carbon and π-donor interactions.…”

“…The 10 target proteins of curcumin in cancer, as previously discussed, are listed in Table 1. 257, Pro 324, Pro 344, Phe 345, and Leu 346, as elucidated in the docking study [108]. The cartoon in Figure 5 was created with BioRender.com (https://app.biorender.com, accessed on 10 January 2024).…”

“…The cartoon in Figure 5 was created with BioRender.com (https://app.biorender.com, accessed on 10 January 2024). 257, Pro 324, Pro 344, Phe 345, and Leu 346, as elucidated in the docking study [108]. The cartoon in Figure 5 was created with BioRender.com (https://app.biorender.com, accessed on 10 January 2024).…”

“…Blue arrows indicate gene expression. The inset presents the interaction between curcumin and NF-κB, highlighting how curcumin blocks the enzyme's function by forming hydrogen bonds with Thr 256, Ala 257, Pro 324, Pro 344, Phe 345, and Leu 346, as elucidated in the docking study [108]. The cartoon in Figure 5 was created with BioRender.com (https://app.biorender.com, accessed on 10 January 2024).…”