Icariin, a flavonoid with anti-cancer effects, alleviated paclitaxel-induced neuropathic pain in a SIRT1-dependent manner.
In: Molecular pain, Jg. 14 (2018), S. 1744806918768970
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Zugriff:
Background One of the most common side effects of paclitaxel was dosage-dependently painful neuropathy. Various reports indicated that spinal neuroinflammation was involved in paclitaxel-induced neuropathic pain. This study investigated the effect of icariin on paclitaxel-induced neuroinflammation and peripheral neuropathy in rats. Methods Two parts were included in this study. In part one, the effect of icariin on paclitaxel-induced neuropathic pain was investigated. Mechanical thresholds were measured as primary outcomes. Production of proinflammatory factors (tumor necrosis factor-α, interleukin-1 β, and interleukin-6), activation of nuclear factor-κB (NF-κB(p65)) signal, and activation of astrocytes were detected as secondary outcomes. Spinal Sirtuin 1 (SIRT1) expression, H4 acetylation, and NAD + content were measured to investigate the effect of icariin on spinal SIRT1 signal pathway. In part two, the role of SIRT1 signal on icariin-induced effect in rats was investigated, and EX527, a SIRT1 inhibitor, was employed. Results The results showed paclitaxel treatment induced significant decrease in mechanical thresholds. Paclitaxel treatment also induced NF-κB(p65) activation and upregulation of proinflammatory factors (TNF-α, IL-1β, and IL-6). Paclitaxel also induced astrocyte activation in the spinal cord. However, 100 mg/kg icariin treatment significantly alleviated paclitaxel-induced mechanical allodynia and spinal neuroinflammation. Furthermore, icariin treatment dosage-dependently reversed paclitaxel-induced SIRT1 downregulation and H4 acetylation. EX527, a selective SIRT1 inhibitor, completely reversed icariin-induced anti-neuroinflammation and anti-allodynia effects in paclitaxel-induced neuropathic pain rats. Conclusions This meant that spinal SIRT1 activation was involved in icariin-induced effects in paclitaxel-induced neuropathic pain rats. Icariin could be a potential agent for the treatment of paclitaxel-induced neuropathic pain.
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Icariin, a flavonoid with anti-cancer effects, alleviated paclitaxel-induced neuropathic pain in a SIRT1-dependent manner.
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Autor/in / Beteiligte Person: | Gui, Y ; Zhang, J ; Chen, L ; Duan, S ; Tang, J ; Xu, W ; Li, A |
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Zeitschrift: | Molecular pain, Jg. 14 (2018), S. 1744806918768970 |
Veröffentlichung: | 2016- : Thousand Oaks, CA : Sage Publications Inc. ; <i>Original Publication</i>: [London] : BioMed Central, 2005-, 2018 |
Medientyp: | academicJournal |
ISSN: | 1744-8069 (electronic) |
DOI: | 10.1177/1744806918768970 |
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