Investigating the mechanism of Xiongfu formula and its active ingredient Z-Ligustilide alleviates chronic migraine by modulating the MAPK/ERK/CREB pathway and microglia-mediated neuroinflammation
Abstract
Ethnopharmacological relevance: Chronic migraine is a recurrent throbbing headache, which is often attributed to stagnated Qi and impaired blood circulation from the perspective of traditional Chinese medicine. Xiongfu formula (CRCR), consisting of Chuanxiong Rhizoma and Cyperi Rhizoma, is a classic herbal formula in treating migraine from the treatise Jingyue Quanshu during the Ming Dynasty.
Aim of the study: This study sought to look at the potential molecular mechanism of CRCR and its active constituents for chronic migraine therapy.
Methods: A rat model of chronic migraine was established by dural infusion of inflammatory soup. Pain-related behavioral assessments and trigeminal nerve injuries were used to evaluate CRCR's efficacy in chronic migraine treatment. RNA-seq, RT-qPCR, western blotting and immunofluorescence assays were applied to identify the potential signaling pathways. The components of CRCR in the blood and brain tissues of chronic migraine rats were quantitatively determined using UPLC-MS/MS. The active ingredient against neuroinflammation in chronic migraine was further validated in BV-2 cell model.
Results: CRCR increased mechanical and thermal pain thresholds and inhibited the central sensitization in chronic migraine rats, suggesting its therapeutic ability in alleviating pain hypersensitivity and trigeminal nerve injuries. Transcriptomic analysis indicated the MAPK signaling pathway as the potential therapeutic target. CRCR suppressed MAPK pathway by…
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