Integrated analysis of blood-absorbed components, metabolomics, and transcriptomics reveals Tianshu Capsule's effective components and mechanisms.

Abstract

BACKGROUND: Migraine is a chronic neurovascular disorder with limited treatment options. Tianshu capsule (TSC), which contains Chuanxiong Rhizoma and Gastrodiae Rhizoma, has shown promising efficacy in alleviating migraine symptoms. However, the underlying mechanism by which TSC exerts its effect has yet to be explored. PURPOSE: This study aimed to investigate the effective components and mechanisms of TSC in a nitroglycerin (NTG)-induced migraine rat model. METHODS: First, the NTG-induced migraine rat model was utilized to evaluate the efficacy of TSC. Subsequently, blood components and metabolites were analyzed by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). A correlation analysis was conducted between metabolic biomarkers and blood components to identify the potentially effective components of TSC. Transcriptomics has been utilized to analyze differential gene expression. Finally, an integrated analysis of metabolomics and transcriptomics was conducted to screen differentially expressed metabolites (DEMs) and differentially expressed genes (DEGs), and to identify their co-involved regulatory pathways. RESULTS: TSC demonstrated significant efficacy in mitigating NTG-induced migraine in a rat model. Metabolomics identified 37 DEMs while transcriptomics revealed 58 DEGs. A correlation analysis between blood-absorbed components and metabolomic biomarkers identified several effective components, including (Z)-ligustilide, coniferyl ferulate, and senkyunolide N. Further analyses indicated that TSC modulated both metabolic and transcriptional profiles, specifically involving the metabolites lysophosphatidylethanolamine (LPE) and O-phospho-L‑serine (L-SOP), while also regulating pivotal genes such as vascular tone modulator Vanin-1 (Vnn-1) and calcium efflux regulator Calsequestrin 2 (Casq2). Collectively, TSC-mediated alterations of metabolites and gene expression regulation reduced calcium (Ca²⁺) levels and inhibited the release of vasoactive peptides, thereby inducing vascular smooth muscle contraction and alleviating migraine. CONCLUSION: In conclusion, TSC significantly improved migraine in rats by regulating metabolites LPE and L-SOP, as well as the gene expressions of Vnn1 and Casq2, which in turn affected vasodilation.