Tetrandrine alleviates oxaliplatin-induced mechanical allodynia via modulation of inflammation-related genes.

Autor: Zhang ZL; Department of Pharmacy, Peking University Third Hospital, Beijing, China., Wu ZY; Department of Pharmacy, Peking University Third Hospital, Beijing, China., Liu FY; Key Laboratory for Neuroscience, Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Ministry of Education/National Health Commission, Peking University, Beijing, China., Hang-YuChen; Department of Pharmacy, Peking University Third Hospital, Beijing, China., Zhai SD; Department of Pharmacy, Peking University Third Hospital, Beijing, China.
Jazyk: angličtina
Zdroj: Frontiers in molecular neuroscience [Front Mol Neurosci] 2024 Feb 14; Vol. 17, pp. 1333842. Date of Electronic Publication: 2024 Feb 14 (Print Publication: 2024).
DOI: 10.3389/fnmol.2024.1333842
Abstrakt: Oxaliplatin, a platinum-based chemotherapy drug, causes neuropathic pain, yet effective pharmacological treatments are lacking. Previously, we showed that tetrandrine (TET), with anti-inflammatory properties, reduces mechanical allodynia in nerve-injured mice. This study explores the effect of TET on oxaliplatin-induced mechanical allodynia and gene changes in mice. Male C57BL/6J mice received oxaliplatin intraperitoneally to induce mechanical allodynia. Post-treatment with TET or vehicle, the mechanical withdrawal threshold (WMT) was assessed using von Frey filaments. TET alleviated oxaliplatin-induced mechanical allodynia. RNA sequencing identified 365 differentially expressed genes (DEGs) in the Control vs. Oxaliplatin group and 229 DEGs in the Oxaliplatin vs. TET group. Pearson correlation analysis of co-regulated DEGs and inflammation-related genes (IRGs) revealed 104 co-regulated inflammation-related genes (Co-IRGs) (|cor| > 0.8, P < 0.01). The top 30 genes in the PPI network were identified. Arg2, Cxcl12, H 2 -Q6, Kdr, and Nfkbia were highlighted based on ROC analysis. Subsequently, Arg2, Cxcl12, Kdr, and Nfkbia were further verified by qRCR. Immune infiltration analysis indicated increased follicular CD4 T cell infiltration in oxaliplatin-treated mice, reduced by TET. Molecular docking showed strong binding affinity between TET and proteins encoded by Arg2, Cxcl12, Kdr, and Nfkbia. In summary, TET may alleviate oxaliplatin-induced peripheral neuropathy in clinical conditions.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Zhang, Wu, Liu, Chen and Zhai.)
Databáze: MEDLINE
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