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Abstract

Introduction

This study aimed to investigate the therapeutic mechanism of coptisine in rotator cuff injury (RCI) through network pharmacology and experimental validation. This is the first study to examine the role of coptisine in rotator cuff injury (RCI), revealing a novel mechanism by which coptisine inhibits the PI3K/Akt/mTOR pathway, thereby coordinating inflammation resolution and tendon repair.

Methods

Network pharmacology was used to identify potential coptisine and RCI targets, which were then analyzed functionally to indicate critical pathways. A rat RCI model (right supraspinatus tendon transection) was used to validate the mechanism by detecting pathological changes, inflammatory factors, and mRNA expression related to the PI3K/Akt/mTOR pathway.

Results and Discussion

Network pharmacology identified 29 overlapping coptisine and RCI targets, with an emphasis on the PI3K/Akt/mTOR pathway. Coptisine reduced tendon atrophy and inflammation in RCI rats, lowered blood TNF-α and IL-6 levels, elevated IL-10, and decreased PI3K, Akt, and mTOR mRNA expression in tendon tissues. These findings align with the pathway-target connection predicted by network pharmacology-specifically, core targets like PIK3CA and PIK3CB (key components of the PI3K/Akt/mTOR pathway) were confirmed to be regulated by coptisine, suggesting the alkaloid exerts anti-inflammatory and tendon-protective effects by suppressing this pathway, which is known to mediate inflammation and protein metabolism in injured tendons.

Conclusion

Coptisine improved RCI in rats by decreasing inflammation and the PI3K/Akt/mTOR pathway, suggesting a possible therapeutic target for RCI.

© 2025 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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2025-10-31
2025-12-05

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Mechanism of Coptisine in Rotator Cuff Injury: PI3K/Akt/mTOR-inflammation Crosstalk Uncovered by Network Pharmacology and Experimental Validation
Bentham Science Publishers ; https://doi.org/10.2174/0115734099394549251014152637
/content/journals/cad/10.2174/0115734099394549251014152637
/content/journals/cad/10.2174/0115734099394549251014152637
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  • Article Type:     Research Article
Keywords: rotator cuff injury ; rat model ; PI3K/Akt/mTOR ; Coptisine ; network pharmacology ; inflammation ; tendon repair

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