Daphnetin alleviates neuropathic pain in chronic constrictive injury rats via regulating the NF-κB dependent CXCL1/CXCR2 signaling pathway

AbstractContext Daphnetin is a natural product with anti-inflammatory, antioxidant, and neuroprotective properties. Reports have found that it has a strong analgesic effect; however, its analgesic mechanism is unknown.Objective We explored the effect and mechanism of daphnetin on neuropathic pain (N...

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Main Authors: Tianrui Zhang, Wulin Liang, Wenjing Ou, Mingqian Zhang, Shuang Cui, Shuofeng Zhang
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Pharmaceutical Biology
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/13880209.2023.2198560
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author Tianrui Zhang
Wulin Liang
Wenjing Ou
Mingqian Zhang
Shuang Cui
Shuofeng Zhang
author_facet Tianrui Zhang
Wulin Liang
Wenjing Ou
Mingqian Zhang
Shuang Cui
Shuofeng Zhang
author_sort Tianrui Zhang
collection DOAJ
description AbstractContext Daphnetin is a natural product with anti-inflammatory, antioxidant, and neuroprotective properties. Reports have found that it has a strong analgesic effect; however, its analgesic mechanism is unknown.Objective We explored the effect and mechanism of daphnetin on neuropathic pain (NP).Materials and methods The rat model of NP was established by ligation of the sciatic nerve. Male Sprague-Dawley rats were divided into six groups: Control, Model, Sham, morphine (0.375 mg/kg), and daphnetin (0.0625 and 0.025 mg/kg). Rats were intrathecally injected with drugs or normal saline once daily for three days. Hyperalgesia was evaluated by mechanical withdrawal threshold (MWT) and thermal withdrawal threshold (TWT). Protein levels were detected using ELISA, immunofluorescence, and western blotting.Results Compared to the Model group, daphnetin improved TWT (46.70 °C vs. 42.20 °C) and MWT (45.60 g vs. 23.60 g), reduced the expression of interleukin-1β (0.99 ng/g vs. 1.42 ng/g), interleukin-6 (0.90 ng/g vs. 1.52 ng/g), and tumor necrosis factor-α (0.93 ng/g vs. 1.52 ng/g) in the sciatic nerve. Daphnetin decreased the expression of toll-like receptor 4 (TLR4) (0.47-fold), phosphorylated inhibitor of NF-κB (p-IKBα) (0.29-fold), nuclear factor kappaB (NF-κB) (0.48-fold), glial fibrillary acidic protein (GFAP) (0.42-fold), CXC chemokine ligand type 1 (CXCL1) (0.84-fold), CXC chemokine receptor type 2 (CXCR2) (0.78-fold) in the spinal cord.Discussion and conclusions Daphnetin alleviates NP by inhibiting inflammation and astrocyte activation in the spinal cord, providing theoretical support for the extensive clinical treatment of NP.
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spelling doaj.art-14369220e5b74db6b5e8d27682e8d6d12024-03-29T11:10:26ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162023-12-0161174675410.1080/13880209.2023.2198560Daphnetin alleviates neuropathic pain in chronic constrictive injury rats via regulating the NF-κB dependent CXCL1/CXCR2 signaling pathwayTianrui Zhang0Wulin Liang1Wenjing Ou2Mingqian Zhang3Shuang Cui4Shuofeng Zhang5Department of Pharmacology of Traditional Chinese Medicine, College of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaDepartment of Pharmacology of Traditional Chinese Medicine, College of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaDepartment of Pharmacology of Traditional Chinese Medicine, College of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaDepartment of Pharmacology of Traditional Chinese Medicine, College of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaDepartment of Pharmacology of Traditional Chinese Medicine, College of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaDepartment of Pharmacology of Traditional Chinese Medicine, College of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaAbstractContext Daphnetin is a natural product with anti-inflammatory, antioxidant, and neuroprotective properties. Reports have found that it has a strong analgesic effect; however, its analgesic mechanism is unknown.Objective We explored the effect and mechanism of daphnetin on neuropathic pain (NP).Materials and methods The rat model of NP was established by ligation of the sciatic nerve. Male Sprague-Dawley rats were divided into six groups: Control, Model, Sham, morphine (0.375 mg/kg), and daphnetin (0.0625 and 0.025 mg/kg). Rats were intrathecally injected with drugs or normal saline once daily for three days. Hyperalgesia was evaluated by mechanical withdrawal threshold (MWT) and thermal withdrawal threshold (TWT). Protein levels were detected using ELISA, immunofluorescence, and western blotting.Results Compared to the Model group, daphnetin improved TWT (46.70 °C vs. 42.20 °C) and MWT (45.60 g vs. 23.60 g), reduced the expression of interleukin-1β (0.99 ng/g vs. 1.42 ng/g), interleukin-6 (0.90 ng/g vs. 1.52 ng/g), and tumor necrosis factor-α (0.93 ng/g vs. 1.52 ng/g) in the sciatic nerve. Daphnetin decreased the expression of toll-like receptor 4 (TLR4) (0.47-fold), phosphorylated inhibitor of NF-κB (p-IKBα) (0.29-fold), nuclear factor kappaB (NF-κB) (0.48-fold), glial fibrillary acidic protein (GFAP) (0.42-fold), CXC chemokine ligand type 1 (CXCL1) (0.84-fold), CXC chemokine receptor type 2 (CXCR2) (0.78-fold) in the spinal cord.Discussion and conclusions Daphnetin alleviates NP by inhibiting inflammation and astrocyte activation in the spinal cord, providing theoretical support for the extensive clinical treatment of NP.https://www.tandfonline.com/doi/10.1080/13880209.2023.2198560Neuralgiadaphnetinastrocytescrosstalkchemokine
spellingShingle Tianrui Zhang
Wulin Liang
Wenjing Ou
Mingqian Zhang
Shuang Cui
Shuofeng Zhang
Daphnetin alleviates neuropathic pain in chronic constrictive injury rats via regulating the NF-κB dependent CXCL1/CXCR2 signaling pathway
Pharmaceutical Biology
Neuralgia
daphnetin
astrocytes
crosstalk
chemokine
title Daphnetin alleviates neuropathic pain in chronic constrictive injury rats via regulating the NF-κB dependent CXCL1/CXCR2 signaling pathway
title_full Daphnetin alleviates neuropathic pain in chronic constrictive injury rats via regulating the NF-κB dependent CXCL1/CXCR2 signaling pathway
title_fullStr Daphnetin alleviates neuropathic pain in chronic constrictive injury rats via regulating the NF-κB dependent CXCL1/CXCR2 signaling pathway
title_full_unstemmed Daphnetin alleviates neuropathic pain in chronic constrictive injury rats via regulating the NF-κB dependent CXCL1/CXCR2 signaling pathway
title_short Daphnetin alleviates neuropathic pain in chronic constrictive injury rats via regulating the NF-κB dependent CXCL1/CXCR2 signaling pathway
title_sort daphnetin alleviates neuropathic pain in chronic constrictive injury rats via regulating the nf κb dependent cxcl1 cxcr2 signaling pathway
topic Neuralgia
daphnetin
astrocytes
crosstalk
chemokine
url https://www.tandfonline.com/doi/10.1080/13880209.2023.2198560
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