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  3. Evaluation of the antimigraine and anti-neuroinflammatory activity of purified constituents of Petasites hybridus L. in a migraine-like pain model in mice

Evaluation of the antimigraine and anti-neuroinflammatory activity of purified constituents of Petasites hybridus L. in a migraine-like pain model in mice

  • Inflammopharmacology. 2026 Feb;34(2):1159-1172. doi: 10.1007/s10787-025-02107-z.
Łukasz Kulinowski 1,  Katarzyna Targowska-Duda 2,  Diana Pietrzak-Mitura 2,  Akanksha Mudgal 2,  Benita Hryć 3,  Łukasz Kurach 4,  Maciej Korczak 5,  Jakub Piwowarski 5,  Simon Vlad Luca 6,  Barbara Budzyńska 4,  Krystyna Skalicka-Woźniak 3
Affiliations

Affiliations

  • 1 Department of Natural Products Chemistry, Medical University of Lublin, 20-093, Lublin, Poland. [email protected].
  • 2 Department of Biopharmacy, Faculty of Pharmacy, Medical University of Lublin, 20-093, Lublin, Poland.
  • 3 Department of Natural Products Chemistry, Medical University of Lublin, 20-093, Lublin, Poland.
  • 4 Independent Laboratory of Behavioral Studies, Medical University of Lublin, 20-093, Lublin, Poland.
  • 5 Microbiota Lab, Department of Pharmaceutical Microbiology and Bioanalysis, Medical University of Warsaw, Banacha 1, 02-097, Warsaw, Poland.
  • 6 Institute of Organic and Analytical Chemistry, CNRS, UMR 7311, University of Orléans, 45067, Orléans, France.
PMID: 41555115 DOI: 10.1007/s10787-025-02107-z
Abstract

Migraine is a prevalent neurovascular disorder strongly associated with neuroinflammation, altered neurotransmitter release, and sensory hypersensitivity. Extracts of Petasites hybridus (butterbur) rootstocks, standardized with eremophilane-type sesquiterpenoids (petasins), have clinically demonstrated efficacy in migraine. However, the pharmacological properties of purified petasins remain insufficiently explored. This study aimed to evaluate their antimigraine and anti-neuroinflammatory potential both in vivo and in vitro. Six sesquiterpenoids were isolated via centrifugal partition chromatography and preparative high-performance liquid chromatography. Male C57BL/6 J mice were subjected to a nitroglycerin model of migraine-like pain, followed by administration of the isolated sesquiterpenoids and mechanical hypersensitivity was evaluated via von Frey filaments. The sesquiterpenoid and neurotransmitter levels in the brain tissues were analyzed via LC‒MS/MS, and the cytokine levels were measured via ELISA. In LPS-stimulated BV-2 microglial cells, anti-inflammatory effects were assessed via Griess assay and a cytokine bead array, and cell viability was measured via MTT assay. Isopetasin significantly attenuated nitroglycerin‒induced mechanical allodynia in both the paw and periorbital regions. These effects may be associated with reduced brain levels of the chemokine CCL2, while LC‒MS/MS confirmed the central bioavailability of isopetasin. In vitro, sesquiterpenoids suppressed LPS‒induced nitric oxide and proinflammatory cytokine release, with isopetasin showing the broadest anti-inflammatory activity. Neurochemical profiling revealed modulation of glutamic acid and GABA associated with the excitatory/inhibitory balance. Purified petasins from butterbur rootstocks, particularly isopetasin, display significant antinociceptive and anti-inflammatory activity in preclinical migraine model. These findings support the importance of well-chemically defined butterbur constituents and provide a foundation for their further investigation as anti-neuroinflammatory agents.

Keywords

Petasites hybridus; Isopetasin; Migraine; Neuroinflammation; Nitroglycerine model; Petasin.

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