Acacetin alleviates neuroinflammation and oxidative stress injury via the Nrf2/HO-1 pathway in a mouse model of spinal cord injury

Spinal cord injury (SCI) is a severe central nervous system disease, which may cause serious locomotor deficit. Acacetin is a flavone that possesses antioxidant and anti-inflammatory effects in different human diseases. The main purpose of this study was to explore whether acacetin ameliorates SCI i...

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Main Authors: Zhang Xin, Xu Lijun, Chen Xiang, Zhou Xianjie, Cao Lanhua
Format: Article
Language:English
Published: De Gruyter 2022-12-01
Series:Translational Neuroscience
Subjects:
Online Access:https://doi.org/10.1515/tnsci-2022-0266
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author Zhang Xin
Xu Lijun
Chen Xiang
Zhou Xianjie
Cao Lanhua
author_facet Zhang Xin
Xu Lijun
Chen Xiang
Zhou Xianjie
Cao Lanhua
author_sort Zhang Xin
collection DOAJ
description Spinal cord injury (SCI) is a severe central nervous system disease, which may cause serious locomotor deficit. Acacetin is a flavone that possesses antioxidant and anti-inflammatory effects in different human diseases. The main purpose of this study was to explore whether acacetin ameliorates SCI in mice. A model of SCI was established in C57BL/6 mice. The Basso Mouse Scale (BMS) score, BMS subscore, mechanical hypersensitivity, and thermal hypersensitivity of mice were tested for determining the motor function. Immunofluorescence staining was utilized to detect NeuN, GFAP, and Iba-1 levels in spinal cord tissues. ELISA was utilized to assess the contents of proinflammatory factors such as interleukin (IL)-1β, IL-18, and tumor necrosis factor-alpha (TNF-α) in spinal cord tissues. The levels of oxidative stress markers, reactive oxygen species, thiobarbituric acid-reactive substances, superoxide dismutase, catalase, glutathione peroxidase, and glutathione were detected using their corresponding kits. Western blot was employed for estimating the levels of heme oxygenase 1 (HO-1), nuclear factor E2-related factor 2 (Nrf2), and Kelch-like ECH-associated protein 1 (Keap-1). In this study, acacetin treatment recovered the motor function in SCI mice. Acacetin improved neuron integrity and repressed glial cell activation in the spinal cord tissues of SCI mice. Furthermore, acacetin administration reduced the SCI-induced high concentrations of IL-1β, IL-18, and TNF-α, as well as inhibited oxidative stress in SCI mice. Moreover, acacetin activated HO-1/Nrf2 pathway in SCI mice. The neuroprotective effects of acacetin against SCI were reversed by Nrf2 inhibitor. Overall, acacetin alleviated neuroinflammation and oxidative stress injury by activating the Nrf2/HO-1 signaling pathway in the mouse models of SCI.
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spelling doaj.art-1dc7e5ecb2dc41e799200ff9c1b9e4ac2023-01-19T13:47:24ZengDe GruyterTranslational Neuroscience2081-69362022-12-0113148349410.1515/tnsci-2022-0266Acacetin alleviates neuroinflammation and oxidative stress injury via the Nrf2/HO-1 pathway in a mouse model of spinal cord injuryZhang Xin0Xu Lijun1Chen Xiang2Zhou Xianjie3Cao Lanhua4Department of Orthopedic, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, No. 141 Tianjin Road, Huangshi 435000, Hubei, ChinaDepartment of Radiology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi 435000, Hubei, ChinaDepartment of Orthopedic, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, No. 141 Tianjin Road, Huangshi 435000, Hubei, ChinaDepartment of Orthopedic, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, No. 141 Tianjin Road, Huangshi 435000, Hubei, ChinaDepartment of Orthopedic, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, No. 141 Tianjin Road, Huangshi 435000, Hubei, ChinaSpinal cord injury (SCI) is a severe central nervous system disease, which may cause serious locomotor deficit. Acacetin is a flavone that possesses antioxidant and anti-inflammatory effects in different human diseases. The main purpose of this study was to explore whether acacetin ameliorates SCI in mice. A model of SCI was established in C57BL/6 mice. The Basso Mouse Scale (BMS) score, BMS subscore, mechanical hypersensitivity, and thermal hypersensitivity of mice were tested for determining the motor function. Immunofluorescence staining was utilized to detect NeuN, GFAP, and Iba-1 levels in spinal cord tissues. ELISA was utilized to assess the contents of proinflammatory factors such as interleukin (IL)-1β, IL-18, and tumor necrosis factor-alpha (TNF-α) in spinal cord tissues. The levels of oxidative stress markers, reactive oxygen species, thiobarbituric acid-reactive substances, superoxide dismutase, catalase, glutathione peroxidase, and glutathione were detected using their corresponding kits. Western blot was employed for estimating the levels of heme oxygenase 1 (HO-1), nuclear factor E2-related factor 2 (Nrf2), and Kelch-like ECH-associated protein 1 (Keap-1). In this study, acacetin treatment recovered the motor function in SCI mice. Acacetin improved neuron integrity and repressed glial cell activation in the spinal cord tissues of SCI mice. Furthermore, acacetin administration reduced the SCI-induced high concentrations of IL-1β, IL-18, and TNF-α, as well as inhibited oxidative stress in SCI mice. Moreover, acacetin activated HO-1/Nrf2 pathway in SCI mice. The neuroprotective effects of acacetin against SCI were reversed by Nrf2 inhibitor. Overall, acacetin alleviated neuroinflammation and oxidative stress injury by activating the Nrf2/HO-1 signaling pathway in the mouse models of SCI.https://doi.org/10.1515/tnsci-2022-0266spinal cord injuryacacetinho-1nrf2
spellingShingle Zhang Xin
Xu Lijun
Chen Xiang
Zhou Xianjie
Cao Lanhua
Acacetin alleviates neuroinflammation and oxidative stress injury via the Nrf2/HO-1 pathway in a mouse model of spinal cord injury
Translational Neuroscience
spinal cord injury
acacetin
ho-1
nrf2
title Acacetin alleviates neuroinflammation and oxidative stress injury via the Nrf2/HO-1 pathway in a mouse model of spinal cord injury
title_full Acacetin alleviates neuroinflammation and oxidative stress injury via the Nrf2/HO-1 pathway in a mouse model of spinal cord injury
title_fullStr Acacetin alleviates neuroinflammation and oxidative stress injury via the Nrf2/HO-1 pathway in a mouse model of spinal cord injury
title_full_unstemmed Acacetin alleviates neuroinflammation and oxidative stress injury via the Nrf2/HO-1 pathway in a mouse model of spinal cord injury
title_short Acacetin alleviates neuroinflammation and oxidative stress injury via the Nrf2/HO-1 pathway in a mouse model of spinal cord injury
title_sort acacetin alleviates neuroinflammation and oxidative stress injury via the nrf2 ho 1 pathway in a mouse model of spinal cord injury
topic spinal cord injury
acacetin
ho-1
nrf2
url https://doi.org/10.1515/tnsci-2022-0266
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AT chenxiang acacetinalleviatesneuroinflammationandoxidativestressinjuryviathenrf2ho1pathwayinamousemodelofspinalcordinjury
AT zhouxianjie acacetinalleviatesneuroinflammationandoxidativestressinjuryviathenrf2ho1pathwayinamousemodelofspinalcordinjury
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