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

doi:10.1016/j.heliyon.2023.e21711

Network pharmacology and in vitro experimental verification to reveal the mechanism of Astragaloside IV against kidney ischemia-reperfusion injury

Heliyon. 2023 Oct 31;9(11):e21711. doi: 10.1016/j.heliyon.2023.e21711. eCollection 2023 Nov.

Authors

Yan Guo^{1

2}, Jinfu Wang³, Yanjie Hua³, Mengya Jiang^{1

2}, Wanyue Xu^{1

2}, Yanpeng Shi⁴, Jiehong Yang³, Haitong Wan³, Ruchun Yang^{1

2}

Affiliations

¹ Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China.
² Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, 310053, China.
³ Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China.
⁴ Linping Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang, 310053, China.

Abstract

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.

Keywords: Astragaloside IV; Ferroptosis; Kidney ischemia-reperfusion injury; Molecular docking; Molecular dynamics simulations; Network pharmacology.