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Linarin attenuates oxaliplatin-induced neuropathic pain by inhibiting NF-κB/NLRP3 signaling pathway


Siyu Zeng
Chenming Ling
Hao Chen
Yu Wang

Abstract

Purpose: To assess the therapeutic effects of linarin on chemotherapy-induced peripheral neuropathy (CINP) in rats.
Methods: A CINP rat model was established using oxaliplatin. The rats were divided into control, CINP, and two linarin treatment groups (20 mg/kg/day and 40 mg/kg/day). Observations were made at various time points, assessing weight gain, mechanical withdrawal thresholds, cold allodynia response, and thermal pain sensitivity. Additionally, the expression levels of various inflammatory factors (IL-1β, IL-6, IL-10, and IL-17), proteins related to glial and neuronal activation (IBA-1, GFAP, c-fos), and proteins linked to NF-κB/NLRP3 signaling (ASC, caspase-1, p65, and p-p65) were evaluated in rat spinal cord tissue.
Results: Linarin treatment resulted in improved weight gain, mechanical threshold, decreased withdrawal response, and enhanced paw withdrawal latency (p < 0.001) compared to the CINP group. These improvements or mitigations were more pronounced in the 40 mg/kg/day linarin group. Linarin inhibited the expression of inflammatory factors IL-1β, IL-6, and IL-17 (p < 0.001) but enhanced IL-10 expression (p < 0.001). The activation of microglia, astrocytes, and neurons, as indicated by IBA-1, GFAP, and c-fos (p < 0.001) proteins, was significantly reduced with linarin, especially at the higher dose. Linarin also suppressed the expression of ASC, caspase-1, p65, and p-p65 (p < 0.001) proteins, associated with the NF-κB/NLRP3 signaling pathway.
Conclusion: Our study indicates that linarin may serve as a potential therapeutic agent for managing CINP. The beneficial effects of linarin are likely mediated through its immunomodulatory effects and the inhibition of the NF-κB/NLRP3 signaling pathway. Further research is needed to confirm these findings in clinical settings.


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eISSN: 1596-9827
print ISSN: 1596-5996