Binary curcuminoid complex CRE-Bin inhibits osteoclast differentiation by suppressing the canonical NF-κB signaling pathway and modulating microRNA-223 expression
Abstract 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...
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| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-04314-8 |
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| author | Sompot Jantarawong Wipapan Khimmaktong Piyawut Swangphon Natda Lauterbach Natthaphon Nanakorn Pharkphoom Panichayupakaranant Yutthana Pengjam |
| author_facet | Sompot Jantarawong Wipapan Khimmaktong Piyawut Swangphon Natda Lauterbach Natthaphon Nanakorn Pharkphoom Panichayupakaranant Yutthana Pengjam |
| author_sort | Sompot Jantarawong |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-e92bc86e1fa54b18a41ad7cf4af59064 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-e92bc86e1fa54b18a41ad7cf4af590642025-08-20T03:03:25ZengNature PortfolioScientific Reports2045-23222025-07-0115111410.1038/s41598-025-04314-8Binary curcuminoid complex CRE-Bin inhibits osteoclast differentiation by suppressing the canonical NF-κB signaling pathway and modulating microRNA-223 expressionSompot Jantarawong0Wipapan Khimmaktong1Piyawut Swangphon2Natda Lauterbach3Natthaphon Nanakorn4Pharkphoom Panichayupakaranant5Yutthana Pengjam6Faculty of Medical Technology, Prince of Songkla UniversityDivision of Health and Applied Sciences, Faculty of Science, Prince of Songkla UniversityFaculty of Medical Technology, Prince of Songkla UniversityFaculty of Medical Technology, Prince of Songkla UniversityFaculty of Medical Technology, Prince of Songkla UniversityDepartment of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla UniversityFaculty of Medical Technology, Prince of Songkla UniversityAbstract 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.https://doi.org/10.1038/s41598-025-04314-8CurcuminoidOsteoclast differentiationmicroRNA-223Nuclear factor I-ACanonical nuclear factor-κB signaling pathway |
| spellingShingle | Sompot Jantarawong Wipapan Khimmaktong Piyawut Swangphon Natda Lauterbach Natthaphon Nanakorn Pharkphoom Panichayupakaranant Yutthana Pengjam Binary curcuminoid complex CRE-Bin inhibits osteoclast differentiation by suppressing the canonical NF-κB signaling pathway and modulating microRNA-223 expression Scientific Reports Curcuminoid Osteoclast differentiation microRNA-223 Nuclear factor I-A Canonical nuclear factor-κB signaling pathway |
| title | Binary curcuminoid complex CRE-Bin inhibits osteoclast differentiation by suppressing the canonical NF-κB signaling pathway and modulating microRNA-223 expression |
| title_full | Binary curcuminoid complex CRE-Bin inhibits osteoclast differentiation by suppressing the canonical NF-κB signaling pathway and modulating microRNA-223 expression |
| title_fullStr | Binary curcuminoid complex CRE-Bin inhibits osteoclast differentiation by suppressing the canonical NF-κB signaling pathway and modulating microRNA-223 expression |
| title_full_unstemmed | Binary curcuminoid complex CRE-Bin inhibits osteoclast differentiation by suppressing the canonical NF-κB signaling pathway and modulating microRNA-223 expression |
| title_short | Binary curcuminoid complex CRE-Bin inhibits osteoclast differentiation by suppressing the canonical NF-κB signaling pathway and modulating microRNA-223 expression |
| title_sort | binary curcuminoid complex cre bin inhibits osteoclast differentiation by suppressing the canonical nf κb signaling pathway and modulating microrna 223 expression |
| topic | Curcuminoid Osteoclast differentiation microRNA-223 Nuclear factor I-A Canonical nuclear factor-κB signaling pathway |
| url | https://doi.org/10.1038/s41598-025-04314-8 |
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