In Silico and Experimental Evidence for Theasaponin E2 as a Modulator of the AKT1/GSK-3β Signaling Axis in Osteoclast Differentiation
4 affiliations
- 1Osteoimmunology & Drug Discovery Research Group, Department of Biology, College of Science, Mathematics and Technology, Wenzhou-Kean University, 88 Daxue Road, Wenzhou 325060, China
- 2Dorothy and George Hennings College of Science, Mathematics and Technology, Kean University, 1000 Morris Ave, Union, NJ 07083, USA
- 3Department of Chemistry, College of Science, Mathematics and Technology, Wenzhou-Kean University, 88 Daxue Road, Wenzhou 325060, China
- 4International Frontier Interdisciplinary Research Institute (IFIRI) of Wenzhou-Kean University, Wenzhou 325060, China
Abstract
Theasaponin E2 (TE2) is a triterpenoid saponin isolated from Camellia sinensis seeds with reported anti-inflammatory, antibacterial, and antitumor activities; however, its effects on osteoclasts remain unclear. In this study, TE2 markedly inhibited RANKL-induced osteoclast differentiation in RAW264.7 cells without affecting precursor-cell viability. TE2 also significantly reduced the number and viability of mature, differentiated osteoclasts. Mechanistically, TE2 suppressed RANKL-induced phosphorylation of AKT at Ser473 and GSK-3β at Ser9, as determined by ELISA. Molecular docking predicted that TE2 could interact with the interdomain allosteric pocket of AKT1 at the pleckstrin homology–kinase domain interface (PDB ID: 7NH5; docking score, −9.8 kcal/mol) and the ATP-binding pocket of GSK-3β (PDB ID: 5K5N; docking score, −7.7 kcal/mol). The selected docking poses contained multiple hydrogen-bonding interactions with donor–acceptor distances of 2.79–3.19 Å. Collectively, these findings indicate that TE2 suppresses osteoclast differentiation and reduces mature osteoclast viability, potentially through modulation of the AKT/GSK-3β signaling axis. TE2 may therefore represent a promising natural-product candidate for further investigation in conditions characterized by excessive osteoclast-mediated bone resorption.
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BibTeX
@article{zhang2026silico,
title = {{In Silico and Experimental Evidence for Theasaponin E2 as a Modulator of the AKT1/GSK-3β Signaling Axis in Osteoclast Differentiation}},
author = {Lifang Zhang and Yili Ding and Xinyi Bao and Vishwa Deepak},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209255},
url = {https://www.mdpi.com/1422-0067/27/20/9255},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - In Silico and Experimental Evidence for Theasaponin E2 as a Modulator of the AKT1/GSK-3β Signaling Axis in Osteoclast Differentiation
AU - Lifang Zhang
AU - Yili Ding
AU - Xinyi Bao
AU - Vishwa Deepak
PY - 2026
DA - 2026/10/18
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209255
UR - https://www.mdpi.com/1422-0067/27/20/9255
AB - Theasaponin E2 (TE2) is a triterpenoid saponin isolated from Camellia sinensis seeds with reported anti-inflammatory, antibacterial, and antitumor activities; however, its effects on osteoclasts remain unclear. In this study, TE2 markedly inhibited RANKL-induced osteoclast differentiation in RAW264.7 cells without affecting precursor-cell viability. TE2 also significantly reduced the number and viability of mature, differentiated osteoclasts. Mechanistically, TE2 suppressed RANKL-induced phosphorylation of AKT at Ser473 and GSK-3β at Ser9, as determined by ELISA. Molecular docking predicted that TE2 could interact with the interdomain allosteric pocket of AKT1 at the pleckstrin homology–kinase domain interface (PDB ID: 7NH5; docking score, −9.8 kcal/mol) and the ATP-binding pocket of GSK-3β (PDB ID: 5K5N; docking score, −7.7 kcal/mol). The selected docking poses contained multiple hydrogen-bonding interactions with donor–acceptor distances of 2.79–3.19 Å. Collectively, these findings indicate that TE2 suppresses osteoclast differentiation and reduces mature osteoclast viability, potentially through modulation of the AKT/GSK-3β signaling axis. TE2 may therefore represent a promising natural-product candidate for further investigation in conditions characterized by excessive osteoclast-mediated bone resorption.
SN - 1422-0067
ER -