Study on the Material Basis and Metabolic Pathways of Shengma–Gegen Decoction in Anti‐Migraine Based on UPLC‐Q‐TOF‐MS and DESI‐MSI Techniques

ABSTRACT “Shengma–Gegen Decoction” (SMGGD), a traditional Chinese herbal formula, is composed of four medicinal herbs, namely, Cimicifugae Rhizoma, Puerariae Lobatae Radix, Paeoniae Radix Alba, and Glycyrrhizae Radix et Rhizoma, and has been proven effective in alleviating headache symptoms. However, the material basis of its pharmacological effects and the metabolic pathways through which it regulates diseases remain unclear. In this study, ultra‐high performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry (UPLC‐Q‐TOF‐MS) was used to detect the aqueous decoction of SMGGD, as well as plasma and brain tissue samples of animals after administration. Combined with desorption electrospray ionization mass spectrometry imaging (DESI‐MSI), the distribution of brain‐penetrating components was analyzed, and the differential endogenous metabolites in brain tissues were enriched. The results showed that a total of 104 chemical components, 39 blood‐entering components, and two brain‐penetrating components were identified from SMGGD. These two brain‐penetrating components were distributed in the prefrontal cortex and thalamus, consistent with the localization of differential metabolites. The differential metabolites were enriched in sphingolipid and glycerophospholipid metabolic pathways. This study clarifies the active components of SMGGD for treating migraine and the metabolic pathways it regulates, providing a theoretical basis for its quality standard research, secondary development, and clinical application.