The effect of hesperidin on trigeminal nerve damage in an NTG-induced migraine model: the role of the TRPV1 channel


Ahlatcı A., Yıldızhan K., Keleş Ö. F., Bayir M. H., ÇINAR R.

Molecular Biology Reports, cilt.53, sa.1, 2026 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 53 Sayı: 1
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1007/s11033-025-11194-8
  • Dergi Adı: Molecular Biology Reports
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE
  • Anahtar Kelimeler: Hesperidin, Migraine, Neuroinflammation, Nitroglycerin, TRPV1 channel
  • Bilecik Şeyh Edebali Üniversitesi Adresli: Evet

Özet

Background: Migraine is a common neurovascular disease associated with trigeminovascular activation and neurogenic inflammation. The transient receptor potential vanilloid-1 (TRPV1) channel plays a central role in nociceptive signalling, while hesperidin (HES), a citrus flavonoid, is known for its antioxidant and neuroprotective properties. This study evaluated the protective effects of HES on TRPV1-mediated pathways in the trigeminal nerve (TGN) in a nitroglycerin (NTG)-induced migraine model. Methods: C57BL/6j mice were randomly assigned to control, NTG, HES + NTG, capsazepine (CPZ) + NTG, and HES + CPZ + NTG groups. Migraine-like pain was induced with NTG (10 mg/kg, i.p.), while HES (200 mg/kg, gavage, 3 days) and CPZ (1 mg/kg, i.p.) were administered as treatments. Behavioral nociceptive assays (tail withdrawal, paw withdrawal, hot plate tests) were performed. The TGN was removed after the mice were killed sacrificed under anesthesia. Substance P, CGRP, BDNF, GSH, MDA, IL-1β, TNF-α, caspase-3, caspase-9, and TRPV1 levels in the TGN were analyzed by an ELISA kit. TRPV1 channel expression was measured in the TGN by western blot analysis. Also, TGN were evaluated histopathologically. Results: NTG significantly induced hyperalgesia, oxidative stress, inflammatory cytokine release, apoptotic activation, and increased TRPV1. HES and CZP treatment significantly attenuated these changes, prolonging nociceptive thresholds, restoring antioxidant defences, suppressing neuropeptides, down-regulating TRPV1, and preserving neuronal morphology. Conclusions: HES treatment and TRPV1 channel inhibition offer a potential therapeutic opportunity for preventive and therapeutic strategies in the treatment of migraine.