Integrated metabolomics and transcriptomics analysis to reveal the mechanism of Xuefu Zhuyu Decoction in the treatment of nitroglycerin-induced chronic migraine.

Migraine is a chronic neurological disorder. As a classic formula for promoting blood circulation and removing blood stasis, Xuefu Zhuyu Decoction (XFZYD) has shown definite clinical efficacy in the treatment of migraine with blood stasis syndrome; however, its biological mechanisms have not yet been fully elucidated and warrant further investigation. Therefore, in this study, we employed untargeted metabolomics, combined with transcriptomic sequencing, to identify endogenous differential metabolites in plasma and differentially expressed genes in brain tissue that were significantly regulated by XFZYD in migraine rats. We further explored the key targets and potential therapeutic mechanisms involved. Through integrated multi-omics analysis, the MAPK/ERK signaling pathway was ultimately identified as the key pathway regulated by XFZYD. Molecular biology experiments further confirmed that XFZYD modulated the expression of genes involved in inflammation, vascular function, and stress response within this pathway, acting on key genes such as COX-2, P-ERK1/2, Nr4a1, and Egr2, thereby intervening in two core pathological processes: vascular dysfunction and neurogenic inflammation. In summary, from both the transcriptomic and terminal metabolic levels, this study systematically elucidated the multidimensional mechanisms by which XFZYD treats migraine by reversing the "blood stasis" state and exerting its effect of "promoting blood circulation and removing blood stasis," thereby providing new research directions and a theoretical basis for its clinical application.