Journal of Southern Medical University ›› 2025, Vol. 45 ›› Issue (5): 986-994.doi: 10.12122/j.issn.1673-4254.2025.05.11

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Huoxue Shufeng Granule alleviates central sensitization in chronic migraine mice via TLR4/NF-κB inflammatory pathway

Xiaotao LIANG1(), Yifan XIONG1, Xueqi LIU5, Xiaoshan LIANG4, Xiaoyu ZHU1, Wei XIE1,2,3,4()   

  1. 1.School of Traditional Chinese Medicine, Southern Medical University
    2.Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics
    3.Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases
    4.Department of Traditional Chinese Medicine, Nanfang Hospital of Southern Medical University, Guangzhou 510515, Guangdong
    5.People's Hospital of Zhuhai High-tech Industrial Development Zone, Zhuhai 519000, Guangdong
  • Received:2025-01-23 Online:2025-05-20 Published:2025-05-23
  • Contact: Wei XIE E-mail:1092296938@qq.com;xieweizn@126.com
  • About author:First author contact:LIANG Xiaotao1, XIONG Yifan1, LIU Xueqi5, LIANG Xiaoshan4, ZHU Xiaoyu1, XIE Wei1, 2, 3, 4

Abstract:

Objective To investigate the therapeutic mechanism of Huoxue Shufeng Granules (HXSFG) for alleviating central sensitization in a mouse model of chronic migraine (CM). Methods We analyzed the main chemical components of HXSFG through literature review and explored their pharmacological mechanisms by bioinformatics analyses. In a male C57BL/6J mouse model of CM established by intraperitoneal injections of nitroglycerin (10 mg/kg) every other day (5 injections), the effects of gavage with low, and high doses of HXSFG or intraperitoneal injections of topiramate for ameliorating central sensitization were evaluated using Von Frey test and a hot plate apparatus; the changes in expressions of inflammatory factors, the proteins in the TLR4/NF‑κB signaling pathway, and activation of c-Fos and CGRP were detected using RT-qPCR, Western blotting and immunofluorescence staining. Results Network pharmacology analysis suggested that the main active components in HXSFG for alleviating CM included formononetin, paeoniflorin, quercetin, and tanshinone. Gene Ontology (GO) enrichment analysis identified 492 GO entries, comprising 366 biological processes, 46 cellular components, and 80 molecular functions. KEGG pathway enrichment analysis indicated that the Toll-like receptor and NF‑κB signaling pathways were crucial in mediating the therapeutic effects of HXSFG on CM. In the mouse models of CM, both topiramate and HXSFG treatments alleviated the symptoms of central sensitization, evidenced by improved mechanical and thermal pain thresholds in the mice. HXSFG significantly reduced the expression of c-Fos and CGRP, improved inflammatory markers, and downregulated the expressions of TLR4, p-NF‑κB, IL-1β, and TNF‑α proteins in the mouse models. Conclusion HXSFG effectively alleviates central sensitization in CM mice by modulating the inflammatory pathways and inhibiting the TLR4/ NF-κB signaling pathway, suggesting its potential as a therapeutic option for CM.

Key words: Huoxue Shufeng Granules, chronic migraine, TLR4/NF-κB, network pharmacology