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Unveiling the therapeutic potential of Dl-3-n-butylphthalide in NTG-induced migraine mouse: activating the Nrf2 pathway to alleviate oxidative stress and neuroinflammation.
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- Author(s): Liu, Yingyuan; Gong, Zihua; Zhai, Deqi; Yang, Chunxiao; Lu, Guangshuang; Wang, Shuqing; Xiao, Shaobo; Li, Chenhao; Chen, Ludan; Lin, Xiaoxue; Zhang, Shuhua; Yu, Shengyuan; Dong, Zhao
- Source:
Journal of Headache & Pain; 4/2/2024, Vol. 25 Issue 1, p1-18, 18p- Subject Terms:
HETEROCYCLIC compounds; BIOLOGICAL models; FREY'S syndrome; SUPEROXIDE dismutase; INTRAPERITONEAL injections; VISION disorders; RESEARCH funding; NEURONS; ENZYME-linked immunosorbent assay; NITROGLYCERIN; NEUROINFLAMMATION; OXIDATIVE stress; CELLULAR signal transduction; TREATMENT effectiveness; ANXIETY; CALCITONIN; DESCRIPTIVE statistics; FLUORESCENT antibody technique; MICE; REACTIVE oxygen species; ANIMAL experimentation; NEUROPEPTIDES; WESTERN immunoblotting; GENE expression profiling; COMPARATIVE studies; CYTOKINES; MIGRAINE; NUCLEAR factor E2 related factor; INTERLEUKINS; TUMOR necrosis factors; MALONDIALDEHYDE - Source:
- Additional Information
- Abstract: Background: Migraine stands as a prevalent primary headache disorder, with prior research highlighting the significant involvement of oxidative stress and inflammatory pathways in its pathogenesis and chronicity. Existing evidence indicates the capacity of Dl-3-n-butylphthalide (NBP) to mitigate oxidative stress and inflammation, thereby conferring neuroprotective benefits in many central nervous system diseases. However, the specific therapeutic implications of NBP in the context of migraine remain to be elucidated. Methods: We established a C57BL/6 mouse model of chronic migraine (CM) using recurrent intraperitoneal injections of nitroglycerin (NTG, 10 mg/kg), and prophylactic treatment was simulated by administering NBP (30 mg/kg, 60 mg/kg, 120 mg/kg) by gavage prior to each NTG injection. Mechanical threshold was assessed using von Frey fibers, and photophobia and anxious behaviours were assessed using a light/dark box and elevated plus maze. Expression of c-Fos, calcitonin gene-related peptide (CGRP), Nucleus factor erythroid 2-related factor 2 (Nrf2) and related pathway proteins in the spinal trigeminal nucleus caudalis (SP5C) were detected by Western blotting (WB) or immunofluorescence (IF). The expression of IL-1β, IL-6, TNF-α, Superoxide dismutase (SOD) and malondialdehyde (MDA) in SP5C and CGRP in plasma were detected by ELISA. A reactive oxygen species (ROS) probe was used to detect the expression of ROS in the SP5C. Results: At the end of the modelling period, chronic migraine mice showed significantly reduced mechanical nociceptive thresholds, as well as photophobic and anxious behaviours. Pretreatment with NBP attenuated nociceptive sensitization, photophobia, and anxiety in the model mice, reduced expression levels of c-Fos and CGRP in the SP5C and activated Nrf2 and its downstream proteins HO-1 and NQO-1. By measuring the associated cytokines, we also found that NBP reduced levels of oxidative stress and inflammation. Most importantly, the therapeutic effect of NBP was significantly reduced after the administration of ML385 to inhibit Nrf2. Conclusions: Our data suggest that NBP may alleviate migraine by activating the Nrf2 pathway to reduce oxidative stress and inflammation in migraine mouse models, confirming that it may be a potential drug for the treatment of migraine. [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of Journal of Headache & Pain is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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