Chuanxiong Qingnao Granules (CQG) alleviates nitroglycerin-induced migraine-like pain in rats by glycerophospholipid metabolism and PI3K/Akt signaling pathway

BACKGROUND AND PURPOSE: Chuanxiong Qingnao Granles (CQG), has been used to treat migraine headache (MH) for many years. However, current investigation of CQG have primarily focused on clinical studies, and the potential mechanisms underlying of its effects on MH have not been fully elucidated. In the present study, we applied an integrated approach of transcriptomics and metabolomics to elucidate the therapeutic mechanisms of CQG in nitroglycerin (NTG)-induced MH injury. METHODS AND RESULTS: Fifty rats were allocated into five random groups: control (Con), NTG, flunarizine (NTG + Flu) group, and two CQG groups (NTG + CQG-L and NTG + CQG-H). CQG notably reduced the duration of ear redness and the frequency of head scratching frequency in rats. It also lowered the levels of 5-hydroxytryptamine (5-HT), endothelin-1 (ET-1), calcitonin gene-related peptide type 1 receptor (CGPR1), and tumor necrosis factor alpha (TNF-α) and enhanced neuronal morphology following NTG-induced MH damage. Transcriptomic and metabolomic analyses pinpointed interleukin (IL)-17A, IL-13, and CC chemokine receptor type 3 (CCR3) as central CQG targets, glycerophospholipid metabolism as key metabolic pathway, and further experiments confirmed that CQG reduced the expression of IL-17A, IL-13, CCR3, and inhibited the expression of inflammatory cytokines by suppressing PI3K/Akt signaling pathway and glycerophospholipid metabolism, to attenuate neuroinflammation in MH rats. CONCLUSIONS: Taken together, CQG inhibited PI3K/Akt signaling pathway to reduced neuroinflammation, and modulated metabolic pathway of glycerophospholipid metabolism in MH. The findings of this study offer novel insights into the mechanisms underlying the therapeutic effects of CQG, highlighting its potential clinical application in treatment of MH.