Abstract
Tanacetum parthenium (feverfew) has traditionally been employed as a phytotherapeutic remedy in the treatment of migraine. In this study, a commercial T. parthenium water extract was investigated to explore its anti-inflammatory and neuromodulatory effects. Isolated mouse cortexes were exposed to a K+ 60 mM Krebs-Ringer buffer and treated with T. parthenium water extract. The prostaglandin E2 (PGE2) level, brain-derived neurotrophic factor (BDNF), interleukin-10 (IL-10), and IL-1β gene expression were evaluated in the cortex. The effects on dopamine (DA) release and dopamine transporter (DAT) gene expression were assayed in hypothalamic HypoE22 cells. A bioinformatics analysis was conducted to further investigate the mechanism of action. The extract was effective in reducing cortex PGE2 release and IL-1β gene expression. In the same experimental system, IL-10 and BDNF gene expressions increased, and in HypoE22 cells, the extract decreased the extracellular dopamine level and increased the DAT gene expression due to the direct interaction of parthenolide with the DAT. Overall, the present findings highlight the efficacy of T. parthenium water extract in controlling the inflammatory pathways that occur during cortical-spreading depression. Additionally, the inhibition of the hypothalamic DA release observed in this study further supports the role of dopaminergic pathways as key targets for novel pharmacological approaches in the management of migraine attacks.
Highlights
Migraine is one of the most prevalent neurovascular disorders, the incidence of which ranges from 8% to 14.7% of people
mass spectrometry (MS) qualitative investigation focused on the presence of parthenolide, the characterizing phytochemical of T. parthenium, and gallic acid and resveratrol, which were previously measured in the extract with independent High-Performance Liquid Chromatography (HPLC)-fluorimetric analysis [23]
The high intensity of the MS signal measured for gallic acid further supported our previous investigation, which showed gallic acid as the most prominent compound in the T. parthenium extract [23]
Summary
Migraine is one of the most prevalent neurovascular disorders, the incidence of which ranges from 8% to 14.7% of people. Hypothalamic orexigenic factors, orexins and dopamine (DA), are possibly involved both in CSD and migraine [10,11,12] In this context, the use of metoclopramide, a DA receptor antagonist, in controlling the clinical symptoms related to migraine [13] is sensible, the recommended first-line treatments for mild to moderate forms of migraine are non-steroidal anti-inflammatory drugs and acetaminophen, whereas triptans are recommended in more severe migraine attacks [14]. Tanacetum parthenium (feverfew), which belongs to the Asteraceae family, has been traditionally employed as a phytotherapeutic remedy in the treatment of migraine [19,20] This use is consistent with the intrinsic antioxidant and anti-inflammatory properties of the active components of the phytocomplex, including flavonoids, volatile oils, and parthenolide [21,22]. The neuromodulatory effects of T. parthenium were described, in the inhibition of
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