Sulforaphane reduced migraine symptoms in mice by modulating the amylin-1 receptor signaling pathway and lowering CGRP levels, performing comparably to the standard migraine drug topiramate.
Comparable to topiramateSulforaphane at 5 mg/kg matched the standard migraine drug topiramate at 30 mg/kg for behavioral symptom improvement in mice
What the researchers found
In female mice with nitroglycerin-induced migraine, sulforaphane (5 mg/kg/day for 9 days) showed significant improvements:
- Behavioral: Reduced photophobia, head grooming, mechanical and thermal allodynia
- Biochemical: Lowered serum nitric oxide, CGRP, and pro-inflammatory cytokines
- Histological: Ameliorated damage in trigeminal ganglia and trigeminal nucleus caudalis
- Molecular: Reduced AMY1 receptor expression in the medulla; inhibited downstream phospho-ERK1/2, P38, and c-Fos signaling
- Enhanced Nrf2/HO-1 antioxidant pathway while suppressing NF-κB/NLRP3/caspase-1 inflammatory cascade
Effects were comparable to the standard migraine medication topiramate (30 mg/kg/day).
Why it matters
The AMY1 receptor is shared by both amylin and CGRP — two peptides increasingly recognized as key players in migraine. Understanding that a natural compound can modulate this receptor pathway adds to the growing toolkit of AMY1/CGRP-targeting approaches for migraine treatment, complementing the existing antibody and gepant therapies.
How the study worked
Female mice received nitroglycerin (10 mg/kg i.p. every other day) to induce migraine. Treatment groups received sulforaphane (5 mg/kg/day i.p.) or topiramate (30 mg/kg/day i.p.) for 9 days. Behavioral testing assessed photophobia, head grooming, and allodynia. Serum markers (NO, CGRP, cytokines), histology (trigeminal ganglia and nucleus), and molecular signaling (AMY1 receptor, ERK, P38, c-Fos, Nrf2, NF-κB pathways) were analyzed.
What this study cannot tell us
This is a mouse study; migraine in rodents is modeled imperfectly compared to human migraine. Sulforaphane was administered by injection, not orally, and bioavailability via different routes may vary. Only female mice were used, and while migraine is more common in women, results may differ in males. The 9-day treatment period is short for a preventive therapy assessment.
How to read the evidence
This is a preclinical animal study with comprehensive behavioral, biochemical, histological, and molecular analysis. While thorough for a mouse study, results require human validation.
When this study was published
Published in 2025, this study reflects current interest in the AMY1 receptor as a novel migraine target distinct from the established CGRP receptor approach.
The bigger picture
This study connects two hot topics in neuropharmacology: the CGRP/amylin peptide system in migraine and natural neuroprotective compounds. The AMY1 receptor, which binds both amylin and CGRP, is emerging as a distinct therapeutic target from the CGRP receptor alone — potentially offering a different approach to migraine treatment than existing anti-CGRP therapies.
Questions still open
- Would oral sulforaphane supplements provide sufficient brain concentrations to affect AMY1 signaling?
- How does AMY1 receptor targeting compare to direct CGRP receptor antagonism in migraine?
- Could sulforaphane-rich diets contribute to migraine prevention in humans?
Common questions
What is the AMY1 receptor and why does it matter for migraines?
Can eating broccoli prevent migraines?
Read the original research
The Role of the AMY1 Receptor Signaling Cascade in the Protective Effect of Sulforaphane Against Nitroglycerin-Induced Migraine in Mice.
Archiv der Pharmazie, 358(9), e70107
Citation
Elbendary, Luejine A; Abdel-Latif, Ghada A; Khattab, Mohamed A; El-Sahar, Ayman E; Sayed, Rabab H. (2025). The Role of the AMY1 Receptor Signaling Cascade in the Protective Effect of Sulforaphane Against Nitroglycerin-Induced Migraine in Mice.. Archiv der Pharmazie, 358(9), e70107. https://doi.org/10.1002/ardp.70107