Neuroprotective Effects of Savinin on LPS-Induced Neuroinflammation In Vivo via Regulating MAPK/NF-κB Pathway and NLRP3 Inflammasome Activation

The traditional herb <i>Eleutherococcus henryi</i> Oliv. is commonly used to treat inflammatory conditions including rheumatism, arthritis, and hepatitis, as well as mental fatigue and amnesia, according to traditional Chinese medicine (TCM) theory. Savinin is a natural lignan obtained f...

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Main Authors: Siqi Tang, Chunying Li, Zongwu Suo, Yi Xu, Kaixin Wei, Lei Zhao, Hao Huang, Xiangqian Liu, Dongxu Liu, Xiaojun Li
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/28/4/1575
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author Siqi Tang
Chunying Li
Zongwu Suo
Yi Xu
Kaixin Wei
Lei Zhao
Hao Huang
Xiangqian Liu
Dongxu Liu
Xiaojun Li
author_facet Siqi Tang
Chunying Li
Zongwu Suo
Yi Xu
Kaixin Wei
Lei Zhao
Hao Huang
Xiangqian Liu
Dongxu Liu
Xiaojun Li
author_sort Siqi Tang
collection DOAJ
description The traditional herb <i>Eleutherococcus henryi</i> Oliv. is commonly used to treat inflammatory conditions including rheumatism, arthritis, and hepatitis, as well as mental fatigue and amnesia, according to traditional Chinese medicine (TCM) theory. Savinin is a natural lignan obtained from the roots of <i>E. henryi</i>. The present study was undertaken to determine whether savinin can relieve LPS-induced neuroinflammation and if so, what the mechanism is. Groups of male C57BL/6 mice were administered savinin (5, 10, 20 mg/kg) and DEX (10 mg/kg) by gavage once daily for a continuous 7 days. On the 5th day of continuous pre-administration, LPS (2.5 mg/kg) was injected into the lateral ventricles of the mice for modeling 48 h. We found that treatment with savinin decreased the levels of neuroinflammatory cytokines and histopathological alterations dramatically. Consequently, it improved the LPS-induced neuroinflammatory response in mice. Furthermore, savinin inhibited the up-regulated expression of related proteins in the activated MAPK/NF-κB and NLRP3 inflammasome signaling pathways caused by LPS. Docking studies demonstrated the binding of savinin to three receptors (MAPK, NF-κB and NLRP3) using a well-fitting mode. These findings suggest that savinin may suppress neuroinflammation induced by LPS in vivo via modulating MAPK/NF-κB and NLRP3 signaling pathways.
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spelling doaj.art-37863fdc038f4dec96efe70c398223602023-11-16T22:20:23ZengMDPI AGMolecules1420-30492023-02-01284157510.3390/molecules28041575Neuroprotective Effects of Savinin on LPS-Induced Neuroinflammation In Vivo via Regulating MAPK/NF-κB Pathway and NLRP3 Inflammasome ActivationSiqi Tang0Chunying Li1Zongwu Suo2Yi Xu3Kaixin Wei4Lei Zhao5Hao Huang6Xiangqian Liu7Dongxu Liu8Xiaojun Li9National Engineering Research Center for Modernization of Traditional Chinese Medicine—Hakka Medical Resources Branch, School of Pharmacy, Gannan Medical University, Ganzhou 341000, ChinaCollege of Basic Medicine, Gannan Medical University, Ganzhou 341000, ChinaNational Engineering Research Center for Modernization of Traditional Chinese Medicine—Hakka Medical Resources Branch, School of Pharmacy, Gannan Medical University, Ganzhou 341000, ChinaNational Engineering Research Center for Modernization of Traditional Chinese Medicine—Hakka Medical Resources Branch, School of Pharmacy, Gannan Medical University, Ganzhou 341000, ChinaNational Engineering Research Center for Modernization of Traditional Chinese Medicine—Hakka Medical Resources Branch, School of Pharmacy, Gannan Medical University, Ganzhou 341000, ChinaCollege of Basic Medicine, Gannan Medical University, Ganzhou 341000, ChinaNational Engineering Research Center for Modernization of Traditional Chinese Medicine—Hakka Medical Resources Branch, School of Pharmacy, Gannan Medical University, Ganzhou 341000, ChinaSchool of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, ChinaCollege of Basic Medicine, Gannan Medical University, Ganzhou 341000, ChinaNational Engineering Research Center for Modernization of Traditional Chinese Medicine—Hakka Medical Resources Branch, School of Pharmacy, Gannan Medical University, Ganzhou 341000, ChinaThe traditional herb <i>Eleutherococcus henryi</i> Oliv. is commonly used to treat inflammatory conditions including rheumatism, arthritis, and hepatitis, as well as mental fatigue and amnesia, according to traditional Chinese medicine (TCM) theory. Savinin is a natural lignan obtained from the roots of <i>E. henryi</i>. The present study was undertaken to determine whether savinin can relieve LPS-induced neuroinflammation and if so, what the mechanism is. Groups of male C57BL/6 mice were administered savinin (5, 10, 20 mg/kg) and DEX (10 mg/kg) by gavage once daily for a continuous 7 days. On the 5th day of continuous pre-administration, LPS (2.5 mg/kg) was injected into the lateral ventricles of the mice for modeling 48 h. We found that treatment with savinin decreased the levels of neuroinflammatory cytokines and histopathological alterations dramatically. Consequently, it improved the LPS-induced neuroinflammatory response in mice. Furthermore, savinin inhibited the up-regulated expression of related proteins in the activated MAPK/NF-κB and NLRP3 inflammasome signaling pathways caused by LPS. Docking studies demonstrated the binding of savinin to three receptors (MAPK, NF-κB and NLRP3) using a well-fitting mode. These findings suggest that savinin may suppress neuroinflammation induced by LPS in vivo via modulating MAPK/NF-κB and NLRP3 signaling pathways.https://www.mdpi.com/1420-3049/28/4/1575savininneuroinflammationMAPKNF-κBNLRP3 inflammasome
spellingShingle Siqi Tang
Chunying Li
Zongwu Suo
Yi Xu
Kaixin Wei
Lei Zhao
Hao Huang
Xiangqian Liu
Dongxu Liu
Xiaojun Li
Neuroprotective Effects of Savinin on LPS-Induced Neuroinflammation In Vivo via Regulating MAPK/NF-κB Pathway and NLRP3 Inflammasome Activation
Molecules
savinin
neuroinflammation
MAPK
NF-κB
NLRP3 inflammasome
title Neuroprotective Effects of Savinin on LPS-Induced Neuroinflammation In Vivo via Regulating MAPK/NF-κB Pathway and NLRP3 Inflammasome Activation
title_full Neuroprotective Effects of Savinin on LPS-Induced Neuroinflammation In Vivo via Regulating MAPK/NF-κB Pathway and NLRP3 Inflammasome Activation
title_fullStr Neuroprotective Effects of Savinin on LPS-Induced Neuroinflammation In Vivo via Regulating MAPK/NF-κB Pathway and NLRP3 Inflammasome Activation
title_full_unstemmed Neuroprotective Effects of Savinin on LPS-Induced Neuroinflammation In Vivo via Regulating MAPK/NF-κB Pathway and NLRP3 Inflammasome Activation
title_short Neuroprotective Effects of Savinin on LPS-Induced Neuroinflammation In Vivo via Regulating MAPK/NF-κB Pathway and NLRP3 Inflammasome Activation
title_sort neuroprotective effects of savinin on lps induced neuroinflammation in vivo via regulating mapk nf κb pathway and nlrp3 inflammasome activation
topic savinin
neuroinflammation
MAPK
NF-κB
NLRP3 inflammasome
url https://www.mdpi.com/1420-3049/28/4/1575
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