Astragaloside IV Relieves Central Sensitization by Regulating Astrocytic ROS/NF‐κB Nuclear Translocation Signaling in Chronic Migraine Male Rats

ABSTRACT Chronic migraine (CM) is a disabling neurological disease. Astragaloside IV (AS‐IV), a natural product derived from Astragalus membranaceus , shows great potential in treating chronic pain by relieving inflammation and oxidative stress. This study aimed to investigate the effects and mechanisms of action of AS‐IV on CM. An inflammatory soup comprising histamine, bradykinin, serotonin, and prostaglandin E2 was used to establish a CM rat model, while lipopolysaccharide was applied to induce an inflammatory response in primary astrocytes. Pain threshold measurements were used to evaluate nociceptive hypersensitivity, while qPCR and Western blotting were applied to detect inflammatory indicators and synaptic protein expression, and Golgi‐Cox staining was applied to observe dendritic spine density, while transmission electron microscopy was used to observe synaptic ultrastructure. Mitochondrial function and oxidative stress were assessed using JC‐1 staining, Mitotracker staining, reactive oxygen species (ROS) quantification, and glutathione content. AS‐IV pretreatment alleviated central sensitization and ameliorated astrocyte activation and neuroinflammation. AS‐IV pretreatment alleviated mitochondrial dysfunction in vitro, and reduced the nuclear translocation of NF‐κB and the production of IL‐1β, which were reversed by ROS scavengers in vitro or mitochondrial respiratory chain disruptors in vivo. Our study indicates that AS‐IV can inhibit neuroinflammation by alleviating astrocyte mitochondrial dysfunction to mitigate central sensitization in CM, thereby providing an experimental basis for AS‐IV and A . membranaceus in CM prevention and treatment.