Neuroscience letters · 2024
Effects of ligustrazine on energy metabolism in migraine rats based on mitochondria-inflammation pathway.
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Wang Yicheng, Wang Yongli, Yue Guangxin, Lin Jingjing, Liu Xueying, Wang Liwei, Zhao Yonglie
Аннотация
OBJECTIVE: To evaluate the effects of Ligustrazine (Lig) on nitroglycerin-induced migraine and explore the mechanism through the mitochondria-inflammation pathway.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.