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Updated: Mar 29, 2026

Studying Chronic Exposure of Mice to Ultraviolet B Radiation
Published on: August 19, 2025
Isaridin E Protects Against UVB-Induced Photoaging by Activating Wnt/β-Catenin Signaling Pathway and Alleviating
Yaosheng Liu1,2, Weizhen Li1,3, Zeen Yang1
1Institute of Dermatology, Guangzhou Medical University, Guangzhou 510095, China.
Abstract:
Mitochondrial dysfunction is a major contributor to skin photoaging. Activation of the Wnt/β-catenin pathway, a key regulator of developmental processes, can improve mitochondrial abnormalities associated with pathology. Therefore, the Wnt/β-catenin pathway emerges as a key therapeutic target in the context of photoaging. Isaridin E (ISE), a marine-derived natural product with a novel structure, exhibits potent antiplatelet and anti-inflammatory activities. We sought to examine the anti-senescence effects of ISE on fibroblasts in photoaged skin. In vitro, ISE improved UVB-induced fibroblast damage in a dose-dependent manner, restoring cell viability, reducing β-galactosidase accumulation, and suppressing SASP factor production. In a photoaging mouse model, ISE markedly decreased skin thickness, increased dermal collagen expression, and reduced SASP levels in skin tissues. ISE significantly improved fibroblast energy production deficits and mitochondrial dysfunction. RNA sequencing and Western blotting demonstrated that UVB irradiation significantly suppressed Wnt/β-catenin signaling activity, whereas ISE dose-dependently restored pathway activation. Using GSK-3β-targeted siRNA, we showed that the anti-photoaging effects of ISE are mediated via the Wnt/β-catenin pathway. ISE appears to counteract photoaging by enhancing Wnt/β-catenin activity and improving mitochondrial function.
Insights
Isaridin E (ISE) combats skin photoaging by improving mitochondrial function and activating the Wnt/β-catenin pathway. This natural compound reduces cellular senescence and restores skin health, offering a potential therapeutic strategy.
Area of Science:
- Dermatology
- Cell Biology
- Molecular Biology
Background:
- Mitochondrial dysfunction significantly contributes to skin photoaging.
- The Wnt/β-catenin pathway is crucial for regulating cellular processes and can ameliorate mitochondrial abnormalities.
- Targeting the Wnt/β-catenin pathway presents a therapeutic avenue for photoaging.
Purpose of the Study:
- To investigate the anti-senescence effects of Isaridin E (ISE) on skin fibroblasts affected by photoaging.
- To elucidate the role of the Wnt/β-catenin pathway in ISE's anti-photoaging mechanisms.
Main Methods:
- In vitro studies using UVB-exposed fibroblasts to assess cell viability, senescence markers (β-galactosidase), and senescence-associated secretory phenotype (SASP) factors.
- In vivo studies utilizing a photoaging mouse model to evaluate skin thickness, collagen expression, and tissue SASP levels.
- RNA sequencing and Western blotting to analyze Wnt/β-catenin signaling pathway activity.
- GSK-3β-targeted siRNA to confirm pathway mediation.
Main Results:
- ISE dose-dependently improved UVB-induced fibroblast damage, reduced senescence markers, and suppressed SASP production.
- In vivo, ISE decreased skin thickness, enhanced dermal collagen, and lowered tissue SASP levels.
- ISE significantly ameliorated mitochondrial dysfunction and energy deficits in fibroblasts.
- UVB irradiation suppressed Wnt/β-catenin signaling, which ISE restored dose-dependently.
- ISE's anti-photoaging effects were confirmed to be mediated through the Wnt/β-catenin pathway.
Conclusions:
- Isaridin E (ISE) demonstrates significant anti-photoaging properties by mitigating UVB-induced skin damage and cellular senescence.
- ISE enhances Wnt/β-catenin pathway activity and improves mitochondrial function, counteracting key aspects of photoaging.
- ISE represents a promising marine-derived natural product for therapeutic intervention in skin photoaging.
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