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.
Calcitonin gene‐related peptide (CGRP) is well‐recognized as a pivotal contributor to the inflammatory process in migraine. Limited evidence suggests that diet may impact circulating levels of CGRP. The objective of this study was to investigate the effects of ginger, turmeric and grape pomace extracts on two cellular models of migraine: CGRP secretion from neuroendocrine CA77 cells, and calcium uptake by nerve growth factor‐differentiated PC12 cells.Dried, ground samples were passed through a 40‐mesh sieve prior to extraction in solvents chosen for their efficiency: grape pomace (50% acetone), ginger root (methanol), and turmeric (acetone). Treatment doses, in 0.1% DMSO vehicle solvent, were based on cell viability results via methylene blue cytoxicity assay. CA77 cells were incubated with treatment for 1 h, then ELISA was used to quantify CGRP. Calcium influx was measured in PC12 cells via the GCaMP5 genetically encoded fluorescent calcium indicator, after 10 min pre‐treatment with extracts, upon stimulation with 50 mM KCl.Results showed a statistically significant decrease in CGRP secretion following treatment with high doses of ginger (0.2 mg ginger equivalent/mL) and grape pomace (1.0 mg pomace equivalent/mL) extracts. Relative to vehicle control, CGRP secretion was decreased by 22% and 87%, respectively. A non‐statistical trend of lower calcium influx was observed in PC12 cells treated with ginger extracts. Solubility of turmeric extracts may have precluded detection of an effect. These results suggest that grape pomace and ginger extracts may have anti‐inflammatory propensity in migraine, which future studies may elucidate.
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