Xiongzhi Qufeng Zhitong Granule alleviates nitroglycerin-induced migraine-like nociception and central neuroinflammation by regulating the HMGB1 / TRPV1 / MAPK signaling axis.
XZQF shows potential in reducing migraine-like symptoms in a rat model, but human studies are needed to confirm its efficacy and safety.
Where it sits
this study against the rest of the vip (vasoactive intestinal polypeptide) corpusSummary and findings
The study evaluated the effects of Xiongzhi Qufeng Zhitong Granules (XZQF) on nitroglycerin-induced chronic migraine in rats. It focused on the HMGB1/TRPV1/MAPK signaling pathway and assessed outcomes using behavioral tests, ELISA, and histopathological analysis. XZQF reduced pro-inflammatory cytokines and pain modulators, suggesting potential anti-migraine effects.
Abstract
Ethnopharmacological relevance Chronic migraine (CM) represents a highly prevalent neuroinflammatory disorder with limited therapeutic options. Xiongzhi Qufeng Zhitong Granules (XZQF), a clinically used traditional Chinese medicine, displays promising anti-migraine potential with favorable safety profiles; however, its systematic efficacy and underlying mechanisms remain poorly defined. Aim of the study This study aimed to investigate the protective effects of XZQF on a CM model in rats triggered by nitroglycerin (NTG) injection, and to unveil the potential mechanisms focusing on HMGB1/TRPV1/MAPK signaling pathway. Materials and methods A CM rat model was first established, and the effects of XZQF on CM were evaluated integrating behavioral testing, enzyme-linked immunosorbent assay (ELISA), and histopathological staining analysis. Subsequently, anti-CM mechanism verification, including network pharmacological analysis, immunofluorescence, immunohistochemistry, and Western blotting, were employed to reveal the molecular mechanism of XZQF in regulating HMGB1/TRPV1/MAPK signaling axis to against CM. Results Both behavioral assays, ELISA test, and histopathological assessment demonstrated that XZQF significantly restored body weight and pain thresholds, reduced serum and brain levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), pain modulators (PGE2, 5-HT, β-EP), and vasoactive mediators (CGRP, VIP, NO, iNOS), while alleviating migraine-associated brain tissue damage. Network pharmacology identified core targets (STAT3, NFKB1, JUN, PTGS2, IL1B) and key bioactive components (ferulic acid, senkyunolides E/F, neocnidilide, methyleugenol), with enrichment in MAPK, PI3K-Akt, and cAMP signaling cascades. Immunofluorescence, immunohistochemistry, and Western blotting further validated that XZQF markedly suppressed the expression of CGRP, TRPV1, c-Fos, COX-2, and HMGB1, as well as the phosphorylation of MEK and MAPK. Conclusion Collectively, these findings demonstrate that XZQF exerts robust analgesic, anti-inflammatory, and vasoregulatory effects against CM by blunting central neuroinflammation through the HMGB1/TRPV1/MAPK signaling axis. Our work establishes a mechanistic framework for understanding the anti-CM activity of XZQF and supports its further development as a therapeutic intervention for CM.
Background
Chronic migraine is a prevalent neuroinflammatory disorder with limited treatment options. Traditional Chinese medicine, Xiongzhi Qufeng Zhitong Granules (XZQF), has shown potential anti-migraine effects. This study investigates its efficacy and underlying mechanisms, focusing on the HMGB1/TRPV1/MAPK signaling pathway, which is implicated in migraine pathophysiology.
Methods
The study used a chronic migraine model in rats induced by nitroglycerin injection. Behavioral testing, ELISA, and histopathological analysis were employed to assess the effects of XZQF. Mechanistic studies included network pharmacological analysis, immunofluorescence, immunohistochemistry, and Western blotting to explore the HMGB1/TRPV1/MAPK signaling axis.
Results
XZQF treatment significantly restored body weight and increased pain thresholds in the rat model. It reduced levels of pro-inflammatory cytokines and pain modulators in serum and brain tissues. Key signaling pathways and molecular targets were identified, and XZQF was shown to suppress specific proteins and phosphorylation events associated with migraine pathology.
Interpretation
The study provides evidence that XZQF may have anti-migraine effects through modulation of the HMGB1/TRPV1/MAPK signaling pathway. While the findings are promising, they are based on an animal model, and the clinical relevance to human migraine patients remains uncertain. Further research is needed to confirm these effects in humans and to assess the clinical significance of the observed changes.
Key findings
- XZQF significantly restored body weight and pain thresholds in rats.
- Reduced serum and brain levels of IL-1β, IL-6, TNF-α, PGE2, 5-HT, β-EP, CGRP, VIP, NO, iNOS.
- Network pharmacology identified core targets: STAT3, NFKB1, JUN, PTGS2, IL1B.
- Immunofluorescence and Western blotting showed suppression of CGRP, TRPV1, c-Fos, COX-2, HMGB1.
- Phosphorylation of MEK and MAPK was markedly suppressed.
Limitations
- rat model, not directly translatable to humans
- mechanistic findings require human validation
- short-term study duration
- single-site study