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10.3390/molecules31122158
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Article

A Plant-Derived Flavonoid, Isobavachin, Promotes Osteogenesis and Alleviates Glucocorticoid-Induced Osteoporosis via Modulation of the ESR1-PI3K/Akt Signaling Pathway

by
Jingran Cui
1,†,
Xuting Song
1,†,
Heran Liu
1,
Zhenhai Cui
1,
Mengmeng Sun
2,3,
Min He
2,3,* and
Meiying Jin
1,*
1
School of Integrated Chinese and Western Medicine, Changchun University of Chinese Medicine, No. 1035, Boshuo Rd, Jingyue Economic Development District, Changchun 130117, China
2
Northeast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, China
3
The Jilin Province School-Enterprise Cooperation Technology Innovation Laboratory of Herbal Efficacy Evaluation Based on Zebrafish Model Organisms, Changchun University of Chinese Medicine, Jingyue Economic Development District, Changchun 130117, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Molecules 2026, 31(12), 2158; https://doi.org/10.3390/molecules31122158
Submission received: 22 May 2026 / Revised: 12 June 2026 / Accepted: 15 June 2026 / Published: 18 June 2026
(This article belongs to the Special Issue Functional Evaluation of Natural Products Using Traditional, Alternative, and Emerging Animal Models)
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Abstract

Background: Glucocorticoid-induced osteoporosis (GIOP) is marked by impaired osteogenesis and reduced bone formation. Isobavachin (IBA), a flavonoid from Psoralea corylifolia, shows multiple potentials in anti-inflammatory and bone metabolism regulations, but its effects against GIOP remain unclear. This study investigated the osteoprotective effects and potential mechanism of IBA using zebrafish GIOP model. Methods: osteoprotective effects of IBA was assessed by fluorescence imaging in a prednisolone-induced zebrafish model, following with osteogenic gene expressions measured by RT-qPCR. Potential targets and pathways of IBA was filtered and predicted by network pharmacology, molecular docking, and molecular dynamics (MD) simulations, and finally validated with a pharmacological rescue experiment using a PI3K-specific inhibitor. Results: IBA improved bone mineralization and upregulated osteogenesis-related genes. Network pharmacology identified the PI3K-Akt pathway as a key pathway, with ESR1, GSK3B, MTOR, and CCND1 as core targets. PI3K inhibition attenuated the osteoprotective effects of IBA and suppressed downstream osteogenic gene expression. Conclusions: IBA alleviates GIOP by modulating the ESR1-associated PI3K-Akt signaling pathway and may serve as a multi-target therapeutic candidate for osteoporosis.
Keywords: Isobavachin; osteoporosis; zebrafish; network pharmacology; PI3K inhibitor Isobavachin; osteoporosis; zebrafish; network pharmacology; PI3K inhibitor

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MDPI and ACS Style

Cui, J.; Song, X.; Liu, H.; Cui, Z.; Sun, M.; He, M.; Jin, M. A Plant-Derived Flavonoid, Isobavachin, Promotes Osteogenesis and Alleviates Glucocorticoid-Induced Osteoporosis via Modulation of the ESR1-PI3K/Akt Signaling Pathway. Molecules 2026, 31, 2158. https://doi.org/10.3390/molecules31122158

AMA Style

Cui J, Song X, Liu H, Cui Z, Sun M, He M, Jin M. A Plant-Derived Flavonoid, Isobavachin, Promotes Osteogenesis and Alleviates Glucocorticoid-Induced Osteoporosis via Modulation of the ESR1-PI3K/Akt Signaling Pathway. Molecules. 2026; 31(12):2158. https://doi.org/10.3390/molecules31122158

Chicago/Turabian Style

Cui, Jingran, Xuting Song, Heran Liu, Zhenhai Cui, Mengmeng Sun, Min He, and Meiying Jin. 2026. "A Plant-Derived Flavonoid, Isobavachin, Promotes Osteogenesis and Alleviates Glucocorticoid-Induced Osteoporosis via Modulation of the ESR1-PI3K/Akt Signaling Pathway" Molecules 31, no. 12: 2158. https://doi.org/10.3390/molecules31122158

APA Style

Cui, J., Song, X., Liu, H., Cui, Z., Sun, M., He, M., & Jin, M. (2026). A Plant-Derived Flavonoid, Isobavachin, Promotes Osteogenesis and Alleviates Glucocorticoid-Induced Osteoporosis via Modulation of the ESR1-PI3K/Akt Signaling Pathway. Molecules, 31(12), 2158. https://doi.org/10.3390/molecules31122158

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