Network pharmacology and in vitro experimental verification to reveal the mechanism of Astragaloside IV against kidney ischemia-reperfusion injury
Yan Guo,
Jinfu Wang,
Yanjie Hua,
Mengya Jiang,
Wanyue Xu,
Yanpeng Shi,
Jiehong Yang,
Haitong Wan,
Ruchun Yang
Affiliations
Yan Guo
Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China; Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, 310053, China
Jinfu Wang
Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China
Yanjie Hua
Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China
Mengya Jiang
Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China; Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, 310053, China
Wanyue Xu
Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China; Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, 310053, China
Yanpeng Shi
Linping Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang, 310053, China
Jiehong Yang
Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China
Haitong Wan
Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China; Corresponding author. Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China
Ruchun Yang
Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China; Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, 310053, China; Corresponding author. Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China.
Ischemic acute kidney injury (AKI) is a prevalent disorder among hospitalized patients worldwide. Astragaloside IV (AS-IV) has been shown to protect against ischemic AKI. However, the specific effects and mechanisms of AS-IV on alleviating kidney ischemia-reperfusion (I/R) injury remain unclear. The objective of this research was to elucidate the regulatory targets and mechanisms through which AS-IV protects kidney I/R injury. A combination of network pharmacology, molecular docking, molecular dynamics (MD) simulation, pharmacodynamic study and Western blot were employed to explore the underlying mechanisms. Network pharmacology revealed that ferroptosis was a potential mechanism of AS-IV against kidney I/R injury. Molecular docking and MD simulations demonstrated strong binding affinity between the GPX4/SLC7A11 and AS-IV. The experimental verification demonstrated that AS-IV improved cell proliferation, decreased the level of ROS and Fe2+, and increased the expressions of GPX4 and SLC7A11 as same as Ferrostatin-1 in OGD/R-injured HUVECs. In conclusion, AS-IV had a significant inhibition on ferroptosis in kidney I/R injury, providing a new perspective for drug development on kidney I/R injury. Definitely, further exploration in vivo is necessary to fully understand whether AS-IV alleviates kidney I/R injury through inhibiting endothelial ferroptosis.
