Impact of Food Components on in vitro Calcitonin Gene-Related Peptide Secretion-A Potential Mechanism for Dietary Influence on Migraine

Nutrients. 2016 Jul 1;8(7):406. doi: 10.3390/nu8070406.


Calcitonin gene-related peptide (CGRP) is a pivotal messenger in the inflammatory process in migraine. Limited evidence indicates that diet impacts circulating levels of CGRP, suggesting that certain elements in the diet may influence migraine outcomes. Interruption of calcium signaling, a mechanism which can trigger CGRP release, has been suggested as one potential route by which exogenous food substances may impact CGRP secretion. The objective of this study was to investigate the effects of foods and a dietary supplement on two migraine-related mechanisms in vitro: CGRP secretion from neuroendocrine CA77 cells, and calcium uptake by differentiated PC12 cells. Ginger and grape pomace extracts were selected for their anecdotal connections to reducing or promoting migraine. S-petasin was selected as a suspected active constituent of butterbur extract, the migraine prophylactic dietary supplement. Results showed a statistically significant decrease in stimulated CGRP secretion from CA77 cells following treatment with ginger (0.2 mg dry ginger equivalent/mL) and two doses of grape pomace (0.25 and 1.0 mg dry pomace equivalent/mL) extracts. Relative to vehicle control, CGRP secretion decreased by 22%, 43%, and 87%, respectively. S-petasin at 1.0 μM also decreased CGRP secretion by 24%. Meanwhile, S-petasin and ginger extract showed inhibition of calcium influx, whereas grape pomace had no effect on calcium. These results suggest that grape pomace and ginger extracts, and S-petasin may have anti-inflammatory propensity by preventing CGRP release in migraine, although potentially by different mechanisms, which future studies may elucidate further.

Keywords: butterbur; calcitonin gene-related peptide; calcium; food trigger; ginger; grape pomace; migraine; petasin.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Calcitonin Gene-Related Peptide / blood
  • Calcitonin Gene-Related Peptide / genetics*
  • Calcitonin Gene-Related Peptide / metabolism*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Fruit / chemistry
  • Migraine Disorders / diagnosis
  • Migraine Disorders / drug therapy
  • Migraine Disorders / genetics*
  • PC12 Cells
  • Plant Extracts / pharmacology*
  • Rats
  • Sesquiterpenes / pharmacology
  • Vitis / chemistry
  • Zingiber officinale / chemistry


  • Anti-Inflammatory Agents
  • Plant Extracts
  • Sesquiterpenes
  • petasin
  • Calcitonin Gene-Related Peptide