Anti-Inflammatory Effect of Columbianetin on Lipopolysaccharide-Stimulated Human Peripheral Blood Mononuclear Cells

Dysregulated inflammation is increasingly considered as the main cause of many diseases on which NOD1/NF-κB pathway plays an important role. Columbianetin (CBT) is derived from the root of the Chinese herb Radix Angelicae Pubescentis for treating inflammatory diseases. Although the anti-inflammatory...

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Main Authors: Junying Lu, Keyong Fang, Shiji Wang, Lingxin Xiong, Chao Zhang, Zhongmin Liu, Xuewa Guan, Ruipeng Zheng, Guoqiang Wang, Jingtong Zheng, Fang Wang
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2018/9191743
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author Junying Lu
Keyong Fang
Shiji Wang
Lingxin Xiong
Chao Zhang
Zhongmin Liu
Xuewa Guan
Ruipeng Zheng
Guoqiang Wang
Jingtong Zheng
Fang Wang
author_facet Junying Lu
Keyong Fang
Shiji Wang
Lingxin Xiong
Chao Zhang
Zhongmin Liu
Xuewa Guan
Ruipeng Zheng
Guoqiang Wang
Jingtong Zheng
Fang Wang
author_sort Junying Lu
collection DOAJ
description Dysregulated inflammation is increasingly considered as the main cause of many diseases on which NOD1/NF-κB pathway plays an important role. Columbianetin (CBT) is derived from the root of the Chinese herb Radix Angelicae Pubescentis for treating inflammatory diseases. Although the anti-inflammatory effect of CBT has been reported, its anti-inflammatory mechanism was poorly studied. In this study, we explored the anti-inflammatory pathway of CBT in lipopolysaccharide- (LPS-) stimulated human peripheral blood mononuclear cell (PBMC) model. Inflammatory cytokine production in culture supernatant was assessed using ELISA assay, and the possible anti-inflammatory pathway of CBT was screened using qPCR array and enrichment analysis with DAVID6.8. To further confirm the targeted pathway of CBT, we pretreated PBMC with the selective NOD1 inhibitor ML130 and then measured the protein levels of the pathway by Western blotting. The result showed that CBT effectively suppressed the expressions of TNF-α, IL-6, MCP-1, and IL-1β in a dose-dependent manner and significantly downregulated 19 out of 32 differentially expressed genes, most of which were involved in the NOD1/NF-κB pathway, and also showed that CBT remarkably inhibited LPS-induced NOD1, RIP2, and NF-κB activation. Furthermore, the inhibitory effects of CBT on NOD1/NF-κB pathways were blocked by ML130. These findings indicated that CBT inhibits the production of inflammatory cytokines induced by LPS involved in the downregulation of NOD1/NF-κB pathways.
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series Mediators of Inflammation
spelling doaj-art-e9922c8eddb8429dbba3989606e24e302025-02-03T06:00:46ZengWileyMediators of Inflammation0962-93511466-18612018-01-01201810.1155/2018/91917439191743Anti-Inflammatory Effect of Columbianetin on Lipopolysaccharide-Stimulated Human Peripheral Blood Mononuclear CellsJunying Lu0Keyong Fang1Shiji Wang2Lingxin Xiong3Chao Zhang4Zhongmin Liu5Xuewa Guan6Ruipeng Zheng7Guoqiang Wang8Jingtong Zheng9Fang Wang10Department of Pathogeny Biology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pathogeny Biology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Intensive Care Unit, First Hospital of Jilin University, Changchun 130021, ChinaDepartment of Pathogeny Biology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pathogeny Biology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Intensive Care Unit, First Hospital of Jilin University, Changchun 130021, ChinaDepartment of Pathogeny Biology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pathogeny Biology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pathogeny Biology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pathogeny Biology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pathogeny Biology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDysregulated inflammation is increasingly considered as the main cause of many diseases on which NOD1/NF-κB pathway plays an important role. Columbianetin (CBT) is derived from the root of the Chinese herb Radix Angelicae Pubescentis for treating inflammatory diseases. Although the anti-inflammatory effect of CBT has been reported, its anti-inflammatory mechanism was poorly studied. In this study, we explored the anti-inflammatory pathway of CBT in lipopolysaccharide- (LPS-) stimulated human peripheral blood mononuclear cell (PBMC) model. Inflammatory cytokine production in culture supernatant was assessed using ELISA assay, and the possible anti-inflammatory pathway of CBT was screened using qPCR array and enrichment analysis with DAVID6.8. To further confirm the targeted pathway of CBT, we pretreated PBMC with the selective NOD1 inhibitor ML130 and then measured the protein levels of the pathway by Western blotting. The result showed that CBT effectively suppressed the expressions of TNF-α, IL-6, MCP-1, and IL-1β in a dose-dependent manner and significantly downregulated 19 out of 32 differentially expressed genes, most of which were involved in the NOD1/NF-κB pathway, and also showed that CBT remarkably inhibited LPS-induced NOD1, RIP2, and NF-κB activation. Furthermore, the inhibitory effects of CBT on NOD1/NF-κB pathways were blocked by ML130. These findings indicated that CBT inhibits the production of inflammatory cytokines induced by LPS involved in the downregulation of NOD1/NF-κB pathways.http://dx.doi.org/10.1155/2018/9191743
spellingShingle Junying Lu
Keyong Fang
Shiji Wang
Lingxin Xiong
Chao Zhang
Zhongmin Liu
Xuewa Guan
Ruipeng Zheng
Guoqiang Wang
Jingtong Zheng
Fang Wang
Anti-Inflammatory Effect of Columbianetin on Lipopolysaccharide-Stimulated Human Peripheral Blood Mononuclear Cells
Mediators of Inflammation
title Anti-Inflammatory Effect of Columbianetin on Lipopolysaccharide-Stimulated Human Peripheral Blood Mononuclear Cells
title_full Anti-Inflammatory Effect of Columbianetin on Lipopolysaccharide-Stimulated Human Peripheral Blood Mononuclear Cells
title_fullStr Anti-Inflammatory Effect of Columbianetin on Lipopolysaccharide-Stimulated Human Peripheral Blood Mononuclear Cells
title_full_unstemmed Anti-Inflammatory Effect of Columbianetin on Lipopolysaccharide-Stimulated Human Peripheral Blood Mononuclear Cells
title_short Anti-Inflammatory Effect of Columbianetin on Lipopolysaccharide-Stimulated Human Peripheral Blood Mononuclear Cells
title_sort anti inflammatory effect of columbianetin on lipopolysaccharide stimulated human peripheral blood mononuclear cells
url http://dx.doi.org/10.1155/2018/9191743
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