Hepatic anti-inflammatory effect of hexane extracts of Dioscorea batatas Decne: Possible suppression of toll-like receptor 4-mediated signaling

Oxymatrine (OMT) is the quinolizidine alkaloid extracted from the Chinese herb Sophora flavescens Ait. that has many pharmacological effects and is used for the treatment of some inflammatory diseases. In this study, RAW264.7 cells and THP-1 differentiated macrophages were pretreated with various concentrations of OMT at 2 h prior to treatment with lipopolysaccharide (LPS) (1.0 μg/mL) for different durations. We detected the anti-inflammatory effect of OMT in LPS-stimulated macrophages and investigated the molecular mechanism. We showed that OMT pretreatment significantly inhibited the LPS-induced secretion of nitric oxide (NO), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) in supernatant, attenuated the mRNA levels of inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, and Toll-like receptor 4 (TLR4), increased TLR4 and phosphorylation of inhibitor of kappa B-alpha (p-IBα) in cytosol, and decreased the nuclear level of nuclear factor-κB (NF-κB) p65 in macrophages. In conclusion, OMT exerts anti-inflammatory properties in LPS-stimulated macrophages by down-regulating the TLR4/NF-κB pathway.

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Ginsenoside Rb1 exerts anti-inflammatory effects in vitro and in vivo by modulating toll-like receptor 4 dimerization and NF-kB/MAPKs signaling pathways

Phytomedicine ◽

10.1016/j.phymed.2020.153197 ◽

2020 ◽

Vol 69 ◽

pp. 153197 ◽

Cited By ~ 5

Author(s):

Hongwei Gao ◽

Naixin Kang ◽

Chao Hu ◽

Ziyu Zhang ◽

Qiongming Xu ◽

...

Keyword(s):

Signaling Pathways ◽

Ginsenoside Rb1 ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Anti Inflammatory

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High Mobility Group Box 1 Promotes Small Intestinal Damage Induced by Nonsteroidal Anti-Inflammatory Drugs through Toll-Like Receptor 4

American Journal Of Pathology ◽

10.1016/j.ajpath.2012.03.039 ◽

2012 ◽

Vol 181 (1) ◽

pp. 98-110 ◽

Cited By ~ 41

Author(s):

Yuji Nadatani ◽

Toshio Watanabe ◽

Tetsuya Tanigawa ◽

Hirohisa Machida ◽

Hirotoshi Okazaki ◽

...

Keyword(s):

High Mobility ◽

High Mobility Group ◽

Intestinal Damage ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Inflammatory Drugs ◽

Small Intestinal ◽

Anti Inflammatory

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Vitamin D inhibits lipopolysaccharide-induced inflammatory response potentially through the Toll-like receptor 4 signalling pathway in the intestine and enterocytes of juvenile Jian carp (Cyprinus carpio var. Jian)

British Journal Of Nutrition ◽

10.1017/s0007114515003256 ◽

2015 ◽

Vol 114 (10) ◽

pp. 1560-1568 ◽

Cited By ~ 21

Author(s):

Jun Jiang ◽

Dan Shi ◽

Xiao-Qiu Zhou ◽

Long Yin ◽

Lin Feng ◽

...

Keyword(s):

Vitamin D ◽

Inflammatory Response ◽

Mrna Expression ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Jian Carp ◽

Pre Treatment ◽

Inflammatory Effect

AbstractThe present study was conducted to investigate the anti-inflammatory effect of vitamin D both in juvenile Jian carp (Cyprinus carpio var. Jian) in vivo and in enterocytes in vitro. In primary enterocytes, exposure to 10 mg lipopolysaccharide (LPS)/l increased lactate dehydrogenase activity in the culture medium (P<0·05) and resulted in a significant loss of cell viability (P<0·05). LPS exposure increased (P<0·05) the mRNA expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8), which was decreased by pre-treatment with 1,25-dihydroxyvitamin D (1,25D3) in a dose-dependent manner (P<0·05). Further results showed that pre-treatment with 1,25D3 down-regulated Toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (Myd88) and NF-κB p65 mRNA expression (P<0·05), suggesting potential mechanisms against LPS-induced inflammatory response. In vivo, intraperitoneal injection of LPS significantly increased TNF-α, IL-1β, IL-6 and IL-8 mRNA expression in the intestine of carp (P<0·05). Pre-treatment of fish with vitamin D3 protected the fish intestine from the LPS-induced increase of TNF-α, IL-1β, IL-6 and IL-8 mainly by downregulating TLR4, Myd88 and NF-κB p65 mRNA expression (P<0·05). These observations suggest that vitamin D could inhibit LPS-induced inflammatory response in juvenile Jian carp in vivo and in enterocytes in vitro. The anti-inflammatory effect of vitamin D is mediated at least in part by TLR4-Myd88 signalling pathways in the intestine and enterocytes of juvenile Jian carp.

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Common Interaction Surfaces of the Toll-Like Receptor 4 Cytoplasmic Domain Stimulate Multiple Nuclear Targets

Molecular and Cellular Biology ◽

10.1128/mcb.23.7.2543-2555.2003 ◽

2003 ◽

Vol 23 (7) ◽

pp. 2543-2555 ◽

Cited By ~ 45

Author(s):

Tapani Ronni ◽

Vishal Agarwal ◽

Michael Haykinson ◽

Margaret E. Haberland ◽

Genhong Cheng ◽

...

Keyword(s):

Target Genes ◽

Interleukin 1 ◽

Adaptor Proteins ◽

Critical Surface ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Tlr4 Signaling ◽

Tir Domain ◽

Anti Inflammatory ◽

Mutant Phenotypes

ABSTRACT Toll-like receptor 4 (TLR4) mediates the host response to lipopolysaccharide (LPS) by promoting the activation of pro- and anti-inflammatory cytokine genes. To activate each gene, numerous signal transduction pathways are required. The adaptor proteins MyD88 and TIRAP contribute to the activation of several and possibly all pathways via direct interactions with TLR4's Toll/interleukin-1 receptor (IL-1R) (TIR) domain. However, additional adaptors that are required for the activation of specific subsets of pathways may exist, which could contribute to the differential regulation of target genes. Furthermore, it remains unknown whether direct interactions that have been reported between TIR domains and other proteins are required for TLR4 signaling. To address these issues, we systematically mutated the TLR4 TIR domain in the context of a CD4/TLR4 fusion protein. Several exposed residues defining at least two structural surfaces were required in macrophages for activation of the proinflammatory IL-12 p40 and anti-inflammatory IL-10 promoters, as well as promoters dependent on individual transcription factors. Interestingly, the same residues were required by all promoters tested, suggesting that the signaling pathways diverge downstream of the adaptors. The mutant phenotypes provide a framework for future studies of TLR4 signaling, as the interaction supported by each critical surface residue will need to be defined.

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