Department of Neurology, The Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, China.
Department of Neurology, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, China.
Neurosci Lett. 2025 Jan 1;844:138035. doi: 10.1016/j.neulet.2024.138035. Epub 2024 Nov 4.
To evaluate the effects of Ligustrazine (Lig) on nitroglycerin-induced migraine and explore the mechanism through the mitochondria-inflammation pathway.
Rats were divided into control, model, Lig(50 mg/kg) + Erastin, Lig(100 mg/kg), Lig(50 mg/kg), and Zolmitriptan groups. Nitroglycerin (NTG) was administered through injection to trigger a migraine. The following parameters were measured: mechanical pain threshold, mitochondrial morphology, levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), Adenosine triphosphate (ATP), and Nitric oxide (NO). The neuronal nitric oxide synthase (nNOS), transient receptor potential A1 (TRPA1), interleukin 1 beta (IL-1β), nuclear factor-kappaB (NF-κB), and calcitonin gene-related peptide (CGRP) were detected by Western blotting and immunohistochemistry.
Compared with the model group, the Lig(100 mg/kg) and Lig(50 mg/kg) groups increased mechanical pain threshold as well as improved abnormal mitochondrial morphology. Moreover, compared with the model group, the Lig(100 mg/kg) and Lig(50 mg/kg) groups demonstrated reduced levels of ROS, and NO, and increased MMP, and ATP. Lig(100 mg/kg) and Lig(50 mg/kg) groups reduced inflammation and oxidative stress by inhibiting certain gene expressions. When Erastin was injected, the effectiveness of Lig decreased, indicating that Lig's therapeutic effect was related to the extent of mPTP opening.
The mitochondria-inflammation pathway plays a critical role in regulating migraine. Lig exerts anti-migraine effects primarily by modulating the mitochondria-inflammation pathway providing a novel perspective on migraine research that is beneficial for its clinical application.
评估川芎嗪（Lig）对硝酸甘油诱导偏头痛的影响，并通过线粒体-炎症途径探讨其机制。
将大鼠分为对照组、模型组、川芎嗪（50mg/kg）+依维莫司、川芎嗪（100mg/kg）、川芎嗪（50mg/kg）和佐米曲坦组。通过注射硝酸甘油（NTG）引发偏头痛。测量以下参数：机械痛阈值、线粒体形态、活性氧（ROS）水平、线粒体膜电位（MMP）、三磷酸腺苷（ATP）和一氧化氮（NO）。通过Western blot 和免疫组化检测神经元型一氧化氮合酶（nNOS）、瞬时受体电位 A1（TRPA1）、白细胞介素 1β（IL-1β）、核因子-κB（NF-κB）和降钙素基因相关肽（CGRP）。
与模型组相比，川芎嗪（100mg/kg）和川芎嗪（50mg/kg）组增加了机械痛阈值，并改善了异常的线粒体形态。此外，与模型组相比，川芎嗪（100mg/kg）和川芎嗪（50mg/kg）组降低了 ROS 和 NO 水平，增加了 MMP 和 ATP。川芎嗪（100mg/kg）和川芎嗪（50mg/kg）组通过抑制某些基因表达减少了炎症和氧化应激。当注射依维莫司时，川芎嗪的疗效降低，表明川芎嗪的治疗效果与 mPTP 开放程度有关。
线粒体-炎症途径在调节偏头痛中起关键作用。川芎嗪通过调节线粒体-炎症途径发挥抗偏头痛作用，为偏头痛研究提供了新视角，有利于其临床应用。
