Abstract

ETHNOPHARMACOLOGICAL RELEVANCE Angelica dahurica radix (ADR), originating from Shennong Bencao Jing, is renowned for its ability to resolve the exterior, disperse cold, and relieve pain. ADR has a history of over one thousand years in treating headache and migraine. AIM OF THE STUDY Neuroinflammation and oxidative stress are critical drivers of migraine pathology. Angelica dahurica (ADR), a venerable medicinal and edible herb derived from Angelica dahurica (Fisch. ex Hoffm.) Benth. et Hook. f. or its variety formosana, demonstrates significant anti-migraine potential; however, its bioactive profile and underlying immunopharmacological mechanisms remain elusive. MATERIALS AND METHODS In this study, we established a comprehensive strategy integrating chemical profiling with systems biology to decode the efficacy of ADR. Using UHPLC-Q-TOF-MS/MS, HS-SPME-GC-MS, and molecular networking, we characterized the chemical constituents and identified bioavailable compounds in the bloodstream. In a nitroglycerin (NTG)-induced rat migraine model, ADR treatment remarkably reversed hyperalgesia. Crucially, an integrated non-targeted metabolomics and transcriptomics analysis, validated by Western blot and immunohistochemistry, unveiled the core therapeutic network. RESULTS We identified byakangelicin, oxypeucedanin hydrate, and bergapten as key absorbed bioactive components. Mechanistically, these compounds exert potent neuroprotective effects by blockading the TRPV1/CaMKII axis and the GNA11/ERK/COX-2 inflammatory cascade. CONCLUSION This study provides novel insights into the pharmacological basis of ADR.