Investigation on the potential targets of Astragaloside IV against intracerebral hemorrhage based on network pharmacology and experimental validation

[Display omitted] •Astragaloside IV plays a critical role on hematoma absorption after ICH.•Astragaloside IV can regulate the PI3K/AKT signaling pathway.•Astragaloside IV can inhibit the NF-κB and promote CD36 phagocytosis. Intracerebral hemorrhage (ICH) is a life-threatening type of stroke that affects millions of individuals worldwide. Astragaloside IV (AS-IV), the main bioactive ingredient in Radix Astragali, has been linked to a variety of pharmacologic actions, including stroke. However, the effects and potential mechanisms of AS-IV on hematoma absorption after ICH are still unknown. The study aims to identify potential targets and regulation mechanisms of AS-IV on hematoma absorption after ICH. Network pharmacology, molecular docking, pharmacodynamic study, and western blot were used in this study to explore the potential mechanisms. The results showed that AS-IV could improve the hematoma absorption and neurological outcomes in collagenase VII induced rat ICH models. Molecular docking results had shown that PI3K and AKT were the potential targets of AS-IV against ICH. The experimental validation showed that AS-IV could reduce phosphorylation expression of PI3K and AKT, thereby inhibiting the NF-κB and increasing CD36 expression. This study demonstrated that AS-IV could play a critical role on hematoma absorption after ICH by regulating the PI3K/AKT signaling pathway and promoting CD36 phagocytosis, which provided a new thought for the drug development of ICH.