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Background <p>Migraine is a neurological disorder and major cause of disability globally, especially in women and young adults. This study aimed to investigate the beneficial effects of polydatin (PD), a natural compound, against nitroglycerin (NTG) induced migraine like headache in mice.</p> Materials and methods <p>Behavioural paradigms included Von Frey filament test, tail flick test, light aversion test and assessment of migraine-associated pain like behaviour. In addition, biochemical investigations were undertaken to determine the effect of PD on migraine associated markers including oxidative stress, nitric oxide (NO) and calcitonin gene related peptide (CGRP). Integrated in vivo, in silico, and network pharmacology approaches were employed to evaluate PD’s antimigraine effects. Statistical significance was set at <i>p</i> &lt; 0.05.</p> Results <p>Treatment with PD attenuated NTG-induced migraine like headache and related behavioural changes. PD-subjected animals exhibited enhanced levels of catalase, glutathione-S-transferase, and glutathione, as well as reduced lipid peroxidation, compared to NTG-only treated animals. Reduction in CGRP and nitrite levels along with reduced expression of neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) was also observed in mouse cortex and trigeminal nucleus caudalis (TNc) after treatment with PD compared with disease controls. Histological sections from PD treated animals from these regions resembled closely with those of controls with improved cell viability. Molecular docking studies suggested that PD docked in the similar binding pocket as that of CGRP, Rimegepant (a CGRP receptor blocker) and Sumatriptan. Network pharmacology revealed potential interaction of hub genes with PD, with proteins like NOS1 (nNOS), NOS2 (iNOS), NOS3, PDE5A, GATM, ARG1 and ARG2 having significant role in network functionality and the potential mediation of PD therapeutic effect.</p> Conclusion <p>PD ameliorated NTG-induced migraine like headache through modulation of NO, CGRP and oxidative stress dependant mechanisms.</p>

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Polydatin as a potential therapeutic agent for migraine: mechanistic insights from experimental, network pharmacology and molecular docking studies

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月7日

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  • Maira Anwar,
  • Ismail Badshah,
  • Reem Altaf,
  • Syed Muzzammil Masaud,
  • Amber Kiyani,
  • Babar Murtaza

摘要

Background

Migraine is a neurological disorder and major cause of disability globally, especially in women and young adults. This study aimed to investigate the beneficial effects of polydatin (PD), a natural compound, against nitroglycerin (NTG) induced migraine like headache in mice.

Materials and methods

Behavioural paradigms included Von Frey filament test, tail flick test, light aversion test and assessment of migraine-associated pain like behaviour. In addition, biochemical investigations were undertaken to determine the effect of PD on migraine associated markers including oxidative stress, nitric oxide (NO) and calcitonin gene related peptide (CGRP). Integrated in vivo, in silico, and network pharmacology approaches were employed to evaluate PD’s antimigraine effects. Statistical significance was set at p < 0.05.

Results

Treatment with PD attenuated NTG-induced migraine like headache and related behavioural changes. PD-subjected animals exhibited enhanced levels of catalase, glutathione-S-transferase, and glutathione, as well as reduced lipid peroxidation, compared to NTG-only treated animals. Reduction in CGRP and nitrite levels along with reduced expression of neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) was also observed in mouse cortex and trigeminal nucleus caudalis (TNc) after treatment with PD compared with disease controls. Histological sections from PD treated animals from these regions resembled closely with those of controls with improved cell viability. Molecular docking studies suggested that PD docked in the similar binding pocket as that of CGRP, Rimegepant (a CGRP receptor blocker) and Sumatriptan. Network pharmacology revealed potential interaction of hub genes with PD, with proteins like NOS1 (nNOS), NOS2 (iNOS), NOS3, PDE5A, GATM, ARG1 and ARG2 having significant role in network functionality and the potential mediation of PD therapeutic effect.

Conclusion

PD ameliorated NTG-induced migraine like headache through modulation of NO, CGRP and oxidative stress dependant mechanisms.