Glycyrrhizin Protects Mice Against Experimental Autoimmune Encephalomyelitis by Inhibiting High-Mobility Group Box 1 (HMGB1) Expression and Neuronal HMGB1 Release

The inflammatory mediator high-mobility group box 1 (HMGB1) plays a critical role in the pathogenesis of human multiple sclerosis (MS) and mouse experimental autoimmune encephalomyelitis (EAE). Glycyrrhizin (GL), a glycoconjugated triterpene extracted from licorice root, has the ability to inhibit t...

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Main Authors: Yan Sun, Huoying Chen, Jiapei Dai, Zhongjun Wan, Ping Xiong, Yong Xu, Zhengrong Han, Weitai Chai, Feili Gong, Fang Zheng
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-07-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2018.01518/full
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author Yan Sun
Yan Sun
Yan Sun
Huoying Chen
Huoying Chen
Jiapei Dai
Jiapei Dai
Zhongjun Wan
Ping Xiong
Yong Xu
Zhengrong Han
Zhengrong Han
Weitai Chai
Weitai Chai
Feili Gong
Fang Zheng
Fang Zheng
Fang Zheng
Fang Zheng
author_facet Yan Sun
Yan Sun
Yan Sun
Huoying Chen
Huoying Chen
Jiapei Dai
Jiapei Dai
Zhongjun Wan
Ping Xiong
Yong Xu
Zhengrong Han
Zhengrong Han
Weitai Chai
Weitai Chai
Feili Gong
Fang Zheng
Fang Zheng
Fang Zheng
Fang Zheng
author_sort Yan Sun
collection DOAJ
description The inflammatory mediator high-mobility group box 1 (HMGB1) plays a critical role in the pathogenesis of human multiple sclerosis (MS) and mouse experimental autoimmune encephalomyelitis (EAE). Glycyrrhizin (GL), a glycoconjugated triterpene extracted from licorice root, has the ability to inhibit the functions of HMGB1; however, GL’s function against EAE has not been thoroughly characterized to date. To determine the benefit of GL as a modulator of neuroinflammation, we used an in vivo study to examine GL’s effect on EAE along with primary cultured cortical neurons to study the GL effect on HMGB1 release. Treatment of EAE mice with GL from onset to the peak stage of disease resulted in marked attenuation of EAE severity, reduced inflammatory cell infiltration and demyelination, decreased tumor necrosis factor-alpha (TNF-α), IFN-γ, IL-17A, IL-6, and transforming growth factor-beta 1, and increased IL-4 both in serum and spinal cord homogenate. Moreover, HMGB1 levels in different body fluids were reduced, accompanied by a decrease in neuronal damage, activated astrocytes and microglia, as well as HMGB1-positive astrocytes and microglia. GL significantly reversed HMGB1 release into the medium induced by TNF-α stimulation in primary cultured cortical neurons. Taken together, the results indicate that GL has a strong neuroprotective effect on EAE mice by reducing HMGB1 expression and release and thus can be used to treat central nervous system inflammatory diseases, such as MS.
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spelling doaj.art-f982f24209b847379073b1d8f7ad00442022-12-22T03:42:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-07-01910.3389/fimmu.2018.01518350535Glycyrrhizin Protects Mice Against Experimental Autoimmune Encephalomyelitis by Inhibiting High-Mobility Group Box 1 (HMGB1) Expression and Neuronal HMGB1 ReleaseYan Sun0Yan Sun1Yan Sun2Huoying Chen3Huoying Chen4Jiapei Dai5Jiapei Dai6Zhongjun Wan7Ping Xiong8Yong Xu9Zhengrong Han10Zhengrong Han11Weitai Chai12Weitai Chai13Feili Gong14Fang Zheng15Fang Zheng16Fang Zheng17Fang Zheng18Wuhan Institute for Neuroscience and Neuroengineering, South-Central University for Nationalities, Wuhan, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurobiology, College of Life Sciences, South-Central University for Nationalities, Wuhan, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Laboratory Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, ChinaWuhan Institute for Neuroscience and Neuroengineering, South-Central University for Nationalities, Wuhan, ChinaDepartment of Neurobiology, College of Life Sciences, South-Central University for Nationalities, Wuhan, ChinaDepartment of Neurobiology, College of Life Sciences, South-Central University for Nationalities, Wuhan, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaWuhan Institute for Neuroscience and Neuroengineering, South-Central University for Nationalities, Wuhan, ChinaDepartment of Neurobiology, College of Life Sciences, South-Central University for Nationalities, Wuhan, ChinaWuhan Institute for Neuroscience and Neuroengineering, South-Central University for Nationalities, Wuhan, ChinaDepartment of Neurobiology, College of Life Sciences, South-Central University for Nationalities, Wuhan, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaKey Laboratory of Organ Transplantation, Ministry of Education, Chinese Academy of Medical Sciences, Wuhan, ChinaNHC Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, ChinaKey Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, ChinaThe inflammatory mediator high-mobility group box 1 (HMGB1) plays a critical role in the pathogenesis of human multiple sclerosis (MS) and mouse experimental autoimmune encephalomyelitis (EAE). Glycyrrhizin (GL), a glycoconjugated triterpene extracted from licorice root, has the ability to inhibit the functions of HMGB1; however, GL’s function against EAE has not been thoroughly characterized to date. To determine the benefit of GL as a modulator of neuroinflammation, we used an in vivo study to examine GL’s effect on EAE along with primary cultured cortical neurons to study the GL effect on HMGB1 release. Treatment of EAE mice with GL from onset to the peak stage of disease resulted in marked attenuation of EAE severity, reduced inflammatory cell infiltration and demyelination, decreased tumor necrosis factor-alpha (TNF-α), IFN-γ, IL-17A, IL-6, and transforming growth factor-beta 1, and increased IL-4 both in serum and spinal cord homogenate. Moreover, HMGB1 levels in different body fluids were reduced, accompanied by a decrease in neuronal damage, activated astrocytes and microglia, as well as HMGB1-positive astrocytes and microglia. GL significantly reversed HMGB1 release into the medium induced by TNF-α stimulation in primary cultured cortical neurons. Taken together, the results indicate that GL has a strong neuroprotective effect on EAE mice by reducing HMGB1 expression and release and thus can be used to treat central nervous system inflammatory diseases, such as MS.https://www.frontiersin.org/article/10.3389/fimmu.2018.01518/fullhigh-mobility group box 1experimental autoimmune encephalomyelitismultiple sclerosisglycyrrhizinneurons
spellingShingle Yan Sun
Yan Sun
Yan Sun
Huoying Chen
Huoying Chen
Jiapei Dai
Jiapei Dai
Zhongjun Wan
Ping Xiong
Yong Xu
Zhengrong Han
Zhengrong Han
Weitai Chai
Weitai Chai
Feili Gong
Fang Zheng
Fang Zheng
Fang Zheng
Fang Zheng
Glycyrrhizin Protects Mice Against Experimental Autoimmune Encephalomyelitis by Inhibiting High-Mobility Group Box 1 (HMGB1) Expression and Neuronal HMGB1 Release
Frontiers in Immunology
high-mobility group box 1
experimental autoimmune encephalomyelitis
multiple sclerosis
glycyrrhizin
neurons
title Glycyrrhizin Protects Mice Against Experimental Autoimmune Encephalomyelitis by Inhibiting High-Mobility Group Box 1 (HMGB1) Expression and Neuronal HMGB1 Release
title_full Glycyrrhizin Protects Mice Against Experimental Autoimmune Encephalomyelitis by Inhibiting High-Mobility Group Box 1 (HMGB1) Expression and Neuronal HMGB1 Release
title_fullStr Glycyrrhizin Protects Mice Against Experimental Autoimmune Encephalomyelitis by Inhibiting High-Mobility Group Box 1 (HMGB1) Expression and Neuronal HMGB1 Release
title_full_unstemmed Glycyrrhizin Protects Mice Against Experimental Autoimmune Encephalomyelitis by Inhibiting High-Mobility Group Box 1 (HMGB1) Expression and Neuronal HMGB1 Release
title_short Glycyrrhizin Protects Mice Against Experimental Autoimmune Encephalomyelitis by Inhibiting High-Mobility Group Box 1 (HMGB1) Expression and Neuronal HMGB1 Release
title_sort glycyrrhizin protects mice against experimental autoimmune encephalomyelitis by inhibiting high mobility group box 1 hmgb1 expression and neuronal hmgb1 release
topic high-mobility group box 1
experimental autoimmune encephalomyelitis
multiple sclerosis
glycyrrhizin
neurons
url https://www.frontiersin.org/article/10.3389/fimmu.2018.01518/full
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