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Updated: Sep 13, 2025
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Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model
Published on: June 6, 2025
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Urolithin A Exhibits Antidepressant-like Effects by Modulating the AMPK/CREB/BDNF Pathway
Yaqian Di1,2, Rui Xue2, Xia Li2
1Key Laboratory of Geriatric Nutrition and Health, Beijing Technology and Business University, Ministry of Education, Beijing 100048, China.
Nutrients
|July 30, 2025
Summary
Urolithin A (UA) demonstrates antidepressant-like effects by protecting brain cells and reducing stress behaviors in animal models. Its benefits are linked to activating the AMPK/CREB/BDNF pathway, suggesting UA as a potential therapeutic for depression.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Urolithin A (UA), a metabolite of ellagitannins, is recognized for potential brain health benefits.
- Depression is a complex disorder with significant unmet therapeutic needs.
- Understanding novel therapeutic targets for depression is crucial.
Purpose of the Study:
- To investigate the antidepressant-like properties of Urolithin A (UA).
- To explore the underlying molecular mechanisms of UA's effects in vitro and in vivo.
- To assess UA's efficacy in cellular and animal models of depression.
Main Methods:
- Investigated UA's effects on corticosterone-induced PC12 cell damage.
- Assessed UA's antidepressant-like activity in mouse tail suspension and forced swim tests.
- Utilized a chronic social defeat stress (CSDS) mouse model to evaluate behavioral and neurobiological changes.
Main Results:
- UA treatment protected PC12 cells from corticosterone-induced damage and inflammation.
- UA significantly reduced immobility in behavioral tests and alleviated depression-like and anxiety-like behaviors in CSDS mice.
- UA activated the AMPK/CREB/BDNF signaling pathway, which was critical for its neuroprotective and behavioral effects.
Conclusions:
- Urolithin A exhibits significant antidepressant-like and anxiolytic-like properties.
- AMPK activation is a key mechanism mediating UA's therapeutic effects.
- UA shows promise as a dietary supplement or therapeutic agent for depression management.
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