The mechanism of Taohe Chengqi decoction in modulating inflammation and alleviating cerebral ischemia-reperfusion injury in rats through regulation of the arachidonic acid metabolism pathway and PI3K/AKT/HIF-1α signaling pathway.

Ischemic stroke (IS) remains a major global cause of mortality, and its incidence continues to increase despite advances in clinical treatment. Taohe Chengqi Decoction (THCQD), a traditional Chinese medicine formulation, has exhibited notable clinical efficacy in cerebral ischemia-reperfusion injury (CIRI), although its active components and mechanisms remain elusive. In this study, an integrated strategy combining liquid chromatography-mass spectrometry (LC-MS), network pharmacology, untargeted metabolomics, and molecular docking was applied to elucidate the bioactive constituents and therapeutic mechanisms of THCQD. A total of 84 compounds were identified, including 22 prototype blood-absorbed constituents, such as emodin, amygdalin, and resveratrol. Network pharmacology indicated that THCQD could primarily regulate the HIF-1 and PI3K/AKT signaling pathways. In a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R), THCQD significantly reduced inflammation and infarct volume, improved neurological function, and preserved brain tissue morphology. Metabolomics analysis further indicated that THCQD could modulate metabolic disturbances, particularly in arachidonic acid and glutathione metabolism. Western blotting and molecular docking confirmed that THCQD components could regulate the "PTGS2/ALOX15-NF-κB/PI3K/AKT-HIF-1α/VEGFA" signaling axis, thereby suppressing neuroinflammation and promoting cellular survival. Overall, these findings demonstrated that THCQD exerted therapeutic effects through multi-component, multi-target mechanisms, involving inflammatory regulation and metabolic restoration, providing new insights into its potential as a holistic treatment strategy for CIRI.