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Gastrodin improves nerve cell injury and behaviors of depressed mice through Caspase‐3‐mediated apoptosis
Aim We investigated the effects and target of gastrodin (GAS) for treating depression through network pharmacology combined with experimentation. Methods The therapeutic target and signal of GAS for depression were analyzed by network pharmacology. Depression in mice was mimicked with a chronic unpr...
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Published in: | CNS neuroscience & therapeutics 2024-03, Vol.30 (3), p.e14444-n/a |
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Main Authors: | , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Aim
We investigated the effects and target of gastrodin (GAS) for treating depression through network pharmacology combined with experimentation.
Methods
The therapeutic target and signal of GAS for depression were analyzed by network pharmacology. Depression in mice was mimicked with a chronic unpredictable mouse stress (CUMS) model. Through open field, elevated plus maze, forced swimming, and tail suspension tests, the effects of GAS on the CUMS mice behaviors were examined, and the levels of neurotransmitters were detected. The histopathological changes were assayed by H&E and IHC staining, and the protein expressions were detected by Western blotting. Small molecule‐protein docking and molecular dynamics experiments were conducted to simulate the binding mode between GAS and Caspase‐3.
Results
Network pharmacological analysis revealed that Caspase‐3 was the action target of GAS. GAS could improve depression‐like behaviors in CUMS mice, elevate their neurotransmitter levels, ameliorate their nerve cell injury, and inhibit their Caspase‐3 expression. After knocking out Caspase‐3, the effects of GAS were inhibited. Molecular dynamics simulation and small molecule‐protein docking found that GAS bound to Caspase‐3 at SER25, inhibiting the maturation and activation of Caspase‐3.
Conclusion
We find that GAS can act as a Caspase‐3 inhibitor, which improves depression‐like behaviors and nerve cell injury in CUMS mice by inhibiting Caspase‐3‐mediated apoptosis.
Gastrodin can act as a Caspase‐3 inhibitor, which improves depression‐like behaviors and nerve cell injury in CUMS mice by inhibiting Caspase‐3‐mediated apoptosis. |
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ISSN: | 1755-5930 1755-5949 |
DOI: | 10.1111/cns.14444 |