https://orcid.org/0000-0002-9709-1070
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Abstract
Background
Astragalus membranaceus (AM) shows promise as a therapeutic agent for osteoarthritis (OA), a debilitating condition with high disability rates. OA exacerbation is linked to chondrocyte ferroptosis, yet the precise pharmacological mechanisms of AM remain unclear.
Methods
We validated AM’s protective efficacy in an anterior cruciate ligament transection (ACLT) mouse model of OA. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database was utilized to identify AM’s active components and their targets. FerrDb (a database for regulators and markers of ferroptosis and ferroptosis-disease associations) pinpointed ferroptosis-related targets, while GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGKB), Therapeutic Target Database (TTD), and DrugBank sourced OA-related genes. Molecular docking analysis further validated these targets. Ultimately, the validation of the results was accomplished through in vitro experiments.
Results
AM exhibited anabolic effects and suppressed catabolism in OA chondrocytes. Network pharmacology identified 19 common genes, and molecular docking suggested quercetin, an AM constituent, interacts with key proteins like HO-1 and NRF2 to inhibit chondrocyte ferroptosis. In vitro experiments confirmed AM’s ability to modulate the NRF2/HO-1 pathway via quercetin, mitigating chondrocyte ferroptosis.
Conclusion
This study elucidates how AM regulates chondrocyte ferroptosis, impacting OA progression, providing a theoretical basis and experimental support for AM’s scientific application.
Data Sharing Statement
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
Ethics Statement
The animal study was reviewed and approved by the Animal Ethics Committee of Nanjing Medical University (DWSY-2101052). All the experiments were conducted under the guidance of the “Guideline for the Care and Use of Laboratory Animals” set by the National Institute for Health of China.
Acknowledgments
We appreciated the laboratory and equipment provided by Central Laboratory, Nanjing First Hospital.
Disclosure
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.