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2000
Volume 26, Issue 1
  • ISSN: 1871-5303
  • E-ISSN: 2212-3873
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Abstract

Introduction

An increase in the intraorbital adipose tissue is the main pathological feature of thyroid-associated ophthalmopathy (TAO). IGF-1R activates PI3K/AKT signaling and accelerates adipogenesis. Pingmu decoction has been demonstrated to promote orbital adipocyte apoptosis; however, less is reported regarding the action mechanism of Danshenol A (DA), a single active ingredient of (Danshen). Accordingly, this study aimed to investigate the role and association of DA and IGF-1R in the proliferation and lipid accumulation of orbital adipocytes.

Methods

Primary human orbital preadipocytes were chosen and authenticated using immunofluorescence. Cells were treated with the IGF-1R agonist ginsenoside Rg5, IGF-1R overexpression plasmid, dexamethasone (Dex), and/or DA, after which cell proliferation and differentiation were assessed by cell counting kit-8 (CCK-8), oil red O staining, real-time quantitative polymerase chain reaction, and Western blot assays.

Results

Orbital preadipocytes showed positive expression of Pref-1. Treatment with IGF-1R agonist, as well as Dex, promoted orbital adipocyte viability and lipid accumulation, and increased the expression of adiponectin and leptin. It was observed that the overexpression of IGF-1R boosted PI3K/AKT activation and elevated PPARγ and C/EBPα expressions. Importantly, DA reversed the effects of IGF-1R on cell viability, lipid accumulation, and the PI3K/AKT signaling pathway.

Discussion

This study, for the first time, revealed the molecular mechanism by which DA regulates orbital fat metabolism through targeted inhibition of the IGF-1R/PI3K/AKT signaling axis. Notably, IGF-1R overexpression partially counteracted the inhibitory effect of DA, suggesting that this component has multi-target regulatory characteristics.

Conclusion

This study not only reveals a new mechanism by which DA treats TAO but also provides theoretical support for the treatment of adipose metabolism.

© 2026 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2026-01-02

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Danshenol A Mediates the Proliferation and Differentiation of Adipocytes in Thyroid-Associated Ophthalmopathy
Endocr Metab Immune Disord Drug Targets 26, E18715303382831 (2026); https://doi.org/10.2174/0118715303382831250712200617
/content/journals/emiddt/10.2174/0118715303382831250712200617
/content/journals/emiddt/10.2174/0118715303382831250712200617
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  • Article Type:     Research Article
Keyword(s): danshenol A; IGF-1R; intraorbital adipose tissues; orbital preadipocytes apoptosis; PI3K/AKT signaling; Thyroid-associated ophthalmopathy

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