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...

Full description

Saved in:
Bibliographic Details
Main Authors: Sompot Jantarawong, Wipapan Khimmaktong, Piyawut Swangphon, Natda Lauterbach, Natthaphon Nanakorn, Pharkphoom Panichayupakaranant, Yutthana Pengjam
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-025-04314-8
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849769401056755712
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
work_keys_str_mv AT sompotjantarawong binarycurcuminoidcomplexcrebininhibitsosteoclastdifferentiationbysuppressingthecanonicalnfkbsignalingpathwayandmodulatingmicrorna223expression
AT wipapankhimmaktong binarycurcuminoidcomplexcrebininhibitsosteoclastdifferentiationbysuppressingthecanonicalnfkbsignalingpathwayandmodulatingmicrorna223expression
AT piyawutswangphon binarycurcuminoidcomplexcrebininhibitsosteoclastdifferentiationbysuppressingthecanonicalnfkbsignalingpathwayandmodulatingmicrorna223expression
AT natdalauterbach binarycurcuminoidcomplexcrebininhibitsosteoclastdifferentiationbysuppressingthecanonicalnfkbsignalingpathwayandmodulatingmicrorna223expression
AT natthaphonnanakorn binarycurcuminoidcomplexcrebininhibitsosteoclastdifferentiationbysuppressingthecanonicalnfkbsignalingpathwayandmodulatingmicrorna223expression
AT pharkphoompanichayupakaranant binarycurcuminoidcomplexcrebininhibitsosteoclastdifferentiationbysuppressingthecanonicalnfkbsignalingpathwayandmodulatingmicrorna223expression
AT yutthanapengjam binarycurcuminoidcomplexcrebininhibitsosteoclastdifferentiationbysuppressingthecanonicalnfkbsignalingpathwayandmodulatingmicrorna223expression