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Background <p>Hispidulin (6-methoxy-4′,5,7-trihydroxyflavone) is a flavonoid commonly found in various plant products, including the leaves of <i>Clerodendrum inerme</i> (L.) Gaertn (CI). While there’s an abundance of literature describing the therapeutic effect of hispidulin and CI in oncological, immunological, and dermatological models, their effect on neuropsychiatric disorders is also of research interest.</p> Objective <p>The previous reports on the neuroprotective and GABA<sub>A</sub> receptor positive modulatory effect of hispidulin may render it as a possible novel candidate as an antimigraine agent.</p> Methods <p>In the present study, we employed the intracisternal instillation of capsaicin in anesthetized rats to induce the activation of trigeminovascular system (TGVS), which mimics the histopathological hallmarks of migraine that include increased neuronal activation in the trigeminal cervical complex (TCC), calcitonin gene-related peptide (CGRP) immunoreactivity in the trigeminal ganglia (TG) and CGRP depletion in the dura mater.</p> Results <p>Administration of hispidulin (4, 10, and 50&#xa0;mg/kg, <i>i.p.</i>) significantly reduced all three TGVS activation parameters induced by <i>i.c.</i> capsaicin. However, pre-treatment of a selective antagonist for α6 subunit-containing GABA<sub>A</sub> receptor, furosemide (20&#xa0;mg/kg, <i>i.p.</i>), did not significantly reverse the antimigraine effect of hispidulin.</p> Conclusion <p>To the best of our knowledge, this is the first report on hispidulin’s suppressive effect on preclinical model of migraine. Further studies are required to explore the mechanism(s) of the antimigraine effect of hispidulin. However, these findings could potentially guide future clinical studies of hispidulin, with the aim of improving human health.</p>

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Hispidulin Isolated from the Leaves of Clerodendrum inerme (L.) Gaertn Suppresses Trigeminovascular System Activation in a Rat Model Mimicking Migraine

  • 期刊论文

  • 发表日期：

    2025年5月9日

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  • Pi-Chuan Fan,
  • Ming Tatt Lee,
  • Tzu-Hsuan Lai,
  • Wei-Jan Huang,
  • Lih-Chu Chiou

摘要

Background

Hispidulin (6-methoxy-4′,5,7-trihydroxyflavone) is a flavonoid commonly found in various plant products, including the leaves of Clerodendrum inerme (L.) Gaertn (CI). While there’s an abundance of literature describing the therapeutic effect of hispidulin and CI in oncological, immunological, and dermatological models, their effect on neuropsychiatric disorders is also of research interest.

Objective

The previous reports on the neuroprotective and GABAA receptor positive modulatory effect of hispidulin may render it as a possible novel candidate as an antimigraine agent.

Methods

In the present study, we employed the intracisternal instillation of capsaicin in anesthetized rats to induce the activation of trigeminovascular system (TGVS), which mimics the histopathological hallmarks of migraine that include increased neuronal activation in the trigeminal cervical complex (TCC), calcitonin gene-related peptide (CGRP) immunoreactivity in the trigeminal ganglia (TG) and CGRP depletion in the dura mater.

Results

Administration of hispidulin (4, 10, and 50 mg/kg, i.p.) significantly reduced all three TGVS activation parameters induced by i.c. capsaicin. However, pre-treatment of a selective antagonist for α6 subunit-containing GABAA receptor, furosemide (20 mg/kg, i.p.), did not significantly reverse the antimigraine effect of hispidulin.

Conclusion

To the best of our knowledge, this is the first report on hispidulin’s suppressive effect on preclinical model of migraine. Further studies are required to explore the mechanism(s) of the antimigraine effect of hispidulin. However, these findings could potentially guide future clinical studies of hispidulin, with the aim of improving human health.