Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

Siyu Zeng , Chenming Ling, Hao Chen, Yu Wang

Department of Neurology, Armed Police Forces Hospital of Sichuan, Leshan City, Sichuan Province 614000, China;

For correspondence:- Siyu Zeng Email: siyu_z18@163.com Tel:+868332452859

Accepted: 31 August 2023 Published: 30 September 2023

Citation: Zeng S, Ling C, Chen H, Wang Y. Linarin attenuates oxaliplatin-induced neuropathic pain by inhibiting NF-κB/NLRP3 signaling pathway. Trop J Pharm Res 2023; 22(9):1797-1803 doi: 10.4314/tjpr.v22i9.5

© 2023 The authors.
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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.

Keywords: Oxaliplatin, Linarin, NF-kappa B; NLRP3 protein, Neurotoxicity, Neuropathic pain