Mechanisms of TQ-6, a Novel Ruthenium-Derivative Compound, against Lipopolysaccharide-Induced In Vitro Macrophage Activation and Liver Injury in Experimental Mice: The Crucial Role of p38 MAPK and NF-κB Signaling

Chih-Hsuan Hsia, Marappan Velusamy, Thanasekaran Jayakumar, Yen-Jen Chen, Chih-Wei Hsia, Jie-Heng Tsai, Ruei-Dun Teng, Joen-Rong Sheu

Research output: Contribution to journalArticle

Abstract

Several studies have reported that metal complexes exhibit anti-inflammatory activities; however, the molecular mechanism is not well understood. In this study, we used a potent ruthenium (II)-derived compound, [Ru(η6-cymene)2-(1H-benzoimidazol-2-yl)-quinoline Cl]BF4 (TQ-6), to investigate the molecular mechanisms underlying the anti-inflammatory effects against lipopolysaccharide (LPS)-induced macrophage activation and liver injury in mice. Treating LPS-stimulated RAW 264.7 cells with TQ-6 suppressed nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in a concentration-dependent manner. The LPS-induced expression of tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) were reduced in TQ-6-treated cells. TQ-6 suppressed, LPS-stimulated p38 MAPK phosphorylation, IκBα degradation, and p65 nuclear translocation in cells. Consistent with the in vitro studies, TQ-6 also suppressed the expression of iNOS, TNF-α, and p65 in the mouse model with acute liver injury induced by LPS. The present study showed that TQ-6 could protect against LPS-induced in vitro inflammation in macrophage and in vivo liver injury in mice, and suggested that NF-κB could be a promising target for protecting against LPS-induced inflammation and liver injury by TQ-6. Therefore, TQ-6 can be a potential therapeutic agent for treating inflammatory diseases.

Original languageEnglish
JournalCells
Volume7
Issue number11
DOIs
Publication statusPublished - Nov 19 2018

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Ruthenium Compounds
Ruthenium
Macrophage Activation
Macrophages
p38 Mitogen-Activated Protein Kinases
Liver
Lipopolysaccharides
Chemical activation
Derivatives
Wounds and Injuries
Nitric Oxide Synthase Type II
Anti-Inflammatory Agents
Tumor Necrosis Factor-alpha
Inflammation
Phosphorylation
Coordination Complexes
In Vitro Techniques
Interleukin-1beta
Nitric Oxide
Cells

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Mechanisms of TQ-6, a Novel Ruthenium-Derivative Compound, against Lipopolysaccharide-Induced In Vitro Macrophage Activation and Liver Injury in Experimental Mice : The Crucial Role of p38 MAPK and NF-κB Signaling. / Hsia, Chih-Hsuan; Velusamy, Marappan; Jayakumar, Thanasekaran; Chen, Yen-Jen; Hsia, Chih-Wei; Tsai, Jie-Heng; Teng, Ruei-Dun; Sheu, Joen-Rong.

In: Cells, Vol. 7, No. 11, 19.11.2018.

Research output: Contribution to journalArticle

Hsia, Chih-Hsuan ; Velusamy, Marappan ; Jayakumar, Thanasekaran ; Chen, Yen-Jen ; Hsia, Chih-Wei ; Tsai, Jie-Heng ; Teng, Ruei-Dun ; Sheu, Joen-Rong. / Mechanisms of TQ-6, a Novel Ruthenium-Derivative Compound, against Lipopolysaccharide-Induced In Vitro Macrophage Activation and Liver Injury in Experimental Mice : The Crucial Role of p38 MAPK and NF-κB Signaling. In: Cells. 2018 ; Vol. 7, No. 11.
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T2 - The Crucial Role of p38 MAPK and NF-κB Signaling

AU - Hsia, Chih-Hsuan

AU - Velusamy, Marappan

AU - Jayakumar, Thanasekaran

AU - Chen, Yen-Jen

AU - Hsia, Chih-Wei

AU - Tsai, Jie-Heng

AU - Teng, Ruei-Dun

AU - Sheu, Joen-Rong

PY - 2018/11/19

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AB - Several studies have reported that metal complexes exhibit anti-inflammatory activities; however, the molecular mechanism is not well understood. In this study, we used a potent ruthenium (II)-derived compound, [Ru(η6-cymene)2-(1H-benzoimidazol-2-yl)-quinoline Cl]BF4 (TQ-6), to investigate the molecular mechanisms underlying the anti-inflammatory effects against lipopolysaccharide (LPS)-induced macrophage activation and liver injury in mice. Treating LPS-stimulated RAW 264.7 cells with TQ-6 suppressed nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in a concentration-dependent manner. The LPS-induced expression of tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) were reduced in TQ-6-treated cells. TQ-6 suppressed, LPS-stimulated p38 MAPK phosphorylation, IκBα degradation, and p65 nuclear translocation in cells. Consistent with the in vitro studies, TQ-6 also suppressed the expression of iNOS, TNF-α, and p65 in the mouse model with acute liver injury induced by LPS. The present study showed that TQ-6 could protect against LPS-induced in vitro inflammation in macrophage and in vivo liver injury in mice, and suggested that NF-κB could be a promising target for protecting against LPS-induced inflammation and liver injury by TQ-6. Therefore, TQ-6 can be a potential therapeutic agent for treating inflammatory diseases.

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KW - nuclear translocation

KW - mice liver injury

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