Edaravone ameliorates inflammation in ischemic stroke mouse by regulating the CYP1A1 pathway through gut microbiota.

Inflammation is one of the main contributors to post-stroke injuries, and the disorders of the gut-brain axis post-stroke can further induce inflammation. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one, EDA) is widely utilized neuroprotective medication for ischemic stroke in Japan, China, India, and other countries. However, the effects of EDA on peripheral inflammation and gut-brain axis repair post-stroke have not been revealed yet. In this study, we employed network pharmacology to identify the potential anti-inflammatory targets and signaling pathways that EDA may influence in the treatment of ischemic stroke. Then, we used 16S rDNA sequencing and molecular docking techniques to determine whether the anti-inflammatory effects of EDA are dependent on the gut-brain axis. Using morphological and molecular biology methods, we investigate how EDA reduces inflammatory response after ischemic stroke through gut microbiota and its metabolites. We demonstrated that EDA alleviated central and peripheral inflammation and rescued gut microbiota dysbiosis post-stroke. Meanwhile, EDA also improved intestinal histological features and decreased intestinal inflammation of post-stroke. The network pharmacology, 16S rDNA sequencing, and molecular docking results revealed that EDA could bind with the ESR1 and thereby regulate the expression of CYP1A1. Furthermore, EDA regulated CYP1A1-related metabolism and decreased the level of 20-HETE post-stroke through gut microbiota. Our study confirmed that EDA alleviated central and peripheral inflammation post-stroke by inhibiting CYP1A1 and CYP1A1-related metabolic through gut microbiota. CYP1A1 was a candidate target for treating ischemic stroke.