秦皮乙素可通过抑制降钙素基因相关肽（CGRP）和调节脑膜肥大细胞减轻大鼠偏头痛样疼痛

Ayca Nur GONUL; Ibrahim Ethem TORUN; Yasemin Baranoglu KILINC; Erkan KILINC

doi:10.1631/jzus.B2500147

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秦皮乙素可通过抑制降钙素基因相关肽（CGRP）和调节脑膜肥大细胞减轻大鼠偏头痛样疼痛

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Research Article | Updated：2026-06-23

秦皮乙素可通过抑制降钙素基因相关肽（CGRP）和调节脑膜肥大细胞减轻大鼠偏头痛样疼痛
Esculetin attenuates migraine-like pain via CGRP suppression and meningeal mast cell modulation in rat models
浙江大学学报（英文版）（B辑：生物医学和生物技术） 2026年27卷第6期页码：615-627
Affiliations：

1.Department of Physiology, Faculty of Medicine, Bolu Abant Izzet Baysal University, Bolu 14030, Türkiye
2.Department of Pediatrics, Faculty of Medicine, Bolu Abant Izzet Baysal University, Bolu 14030, Türkiye
3.Department of Physiology, Cerrahpasa Faculty of Medicine, İstanbul University-Cerrahpaşa, İstanbul 34098, Türkiye
Funds：

Funding note: Open access funding provided by the Scientific and Technological Research Council of Türkiye (TÜBİTAK)
DOI：10.1631/jzus.B2500147
中图分类号：
CSTR：
收稿：2025-03-26，

修回：2025-09-01，

网络首发：2026-05-01，

纸质出版：2026-06-15
Accepted：

Ayca Nur GONUL,Ibrahim Ethem TORUN,Yasemin Baranoglu KILINC等.秦皮乙素可通过抑制降钙素基因相关肽（CGRP）和调节脑膜肥大细胞减轻大鼠偏头痛样疼痛[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2026,27(06):615-627.

Ayca Nur GONUL, Ibrahim Ethem TORUN, Yasemin Baranoglu KILINC, et al. Esculetin attenuates migraine-like pain via CGRP suppression and meningeal mast cell modulation in rat models[J]. Journal of Zhejiang University-SCIENCE B, 2026, 27(6): 615-627.
Ayca Nur GONUL,Ibrahim Ethem TORUN,Yasemin Baranoglu KILINC等.秦皮乙素可通过抑制降钙素基因相关肽（CGRP）和调节脑膜肥大细胞减轻大鼠偏头痛样疼痛[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2026,27(06):615-627. DOI： 10.1631/jzus.B2500147.

Ayca Nur GONUL, Ibrahim Ethem TORUN, Yasemin Baranoglu KILINC, et al. Esculetin attenuates migraine-like pain via CGRP suppression and meningeal mast cell modulation in rat models[J]. Journal of Zhejiang University-SCIENCE B, 2026, 27(6): 615-627. DOI： 10.1631/jzus.B2500147.

摘要

越来越多的证据表明，秦皮乙素作为一种5-脂氧合酶抑制剂，因其具有强效抗炎、抗伤害感受及γ-氨基丁酸A型（GABA

）受体部分激动活性等多种药理学特性，而显示出药物治疗潜力。然而，其对偏头痛的治疗效果仍有待探索。因此，本研究探讨了秦皮乙素在大鼠偏头痛样状态下相关机制的影响。通过体内实验测试了三种不同剂量（5、10和20 mg/kg）的秦皮乙素在硝酸甘油（NTG）诱导的偏头痛模型中的全身性效应；同时，通过体外实验检测了其对三叉神经血管系统关键结构（三叉神经节、三叉神经核以及脑膜传入神经）释放降钙素基因相关肽（CGRP）的直接作用。两组实验均以舒马普坦为阳性对照。体内实验结果显示，秦皮乙素减轻了NTG诱导的机械性痛觉过敏，降低了三叉神经CGRP和c-Fos表达水平，并减少了脑膜肥大细胞脱颗粒和数量；体外实验表明，秦皮乙素能抑制NTG刺激下的三叉神经血管组织块（脑膜组织块除外）的CGRP释放。舒马普坦可逆转两组实验中NTG诱发的变化。综上所述，秦皮乙素能抗伤害感受活性，降低三叉神经血管的CGRP浓度，并减轻脑膜肥大细胞的脱颗粒，因此可作为一种缓解偏头痛的治疗选择，但仍需进一步研究来加以证实。

Abstract

Growing evidence suggests that esculetin

a 5-lipoxygenase inhibitor

has pharmacotherapeutic potential due to its various pharmacological properties

such as potent anti-inflammatory

anti-nociceptive

and γ-aminobutyric acid type A (GABA

) receptor partial agonist activities. However

the effects of this promising agent on migraine remain unexplored. This study therefore examined the impact of esculetin on relevant mechanisms in migraine-like conditions in rats. The systemic effects of esculetin at three distinct doses (5

and 20 mg/kg) were tested in a nitroglycerin (NTG)-induced migraine model using in vivo experimental sets. The direct action of esculetin on the release of calcitonin gene-related peptide (CGRP) from critical structures of the trigeminovascular system (trigeminal ganglion

trigeminal nucleus

and meningeal afferents) was also tested in ex vivo experimental sets. Sumatriptan was used as a positive control in both sets of experiments. The in vivo results showed that esculetin reduced NTG-induced mechanical hyperalgesia and decreased trigeminal CGRP and cellular Fos proto-oncogene (c-Fos) levels. It also decreased degranulation and meningeal mast cell numbers. The ex vivo results revealed that esculetin reduced NTG-stimulated CGRP release from trigeminovascular explants

with the exception of meningeal explants. Sumatriptan reversed the NTG-induced changes in both experimental

sets. Our findings suggest that esculetin exhibits anti-nociceptive activities in experimental migraine conditions

alleviating trigeminovascular CGRP concentrations and the degranulation of meningeal mast cells. Esculetin may thus represent a therapeutic option for relieving migraine headaches

although further research is needed to confirm this.

关键词

Keywords

references

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