Toll-like receptor 4 (TLR4) inhibitors: Current research and prospective

Zhang, Yongsheng; Liang, Xinjie; Bao, Xuefei; Xiao, Wei; Chen, Guoliang

doi:10.1016/j.ejmech.2022.114291

Cited by 115 publications

(69 citation statements)

References 123 publications

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“…The effects of LPS are mediated through its interaction with several receptors for microbial products comprising Toll-like receptors (TLRs) that are a group of type 1 transmembrane proteins able to recognize a variety of molecular signals, including endogenous-damage- and pathogen-associated signals. The best-studied member of the TLR family is TLR-4, involved in the recognition of endotoxins or bacterial LPS [ 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Influence of Polydatin on the Tumor Microenvironment In Vitro: Studies with a Colon Cancer Cell Model

Gregorio

Krasnowska

Zonfrillo

et al. 2022

IJMS

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The tumor microenvironment of colon carcinoma, the site at which tumor cells and the host immune system interact, is influenced by signals from tumor cells, immunocompetent cells, and bacterial components, including LPS. A large amount of LPS is available in the colon, and this could promote inflammation and metastasis by enhancing tumor cell adhesion to the endothelium. Polydatin (PD), the 3-β-D-glucoside of trans-resveratrol, is a polyphenol with anti-cancer, anti-inflammatory, and immunoregulatory effects. This study was designed to explore whether PD is able to produce antiproliferative effects on three colon cancer lines, to reduce the expression of adhesion molecules that are upregulated by LPS on endothelial cells, and to decrease the proinflammatory cytokines released in culture supernatants. Actually, we investigated the effects of PD on tumor growth in a coculture model with human mononuclear cells (MNCs) that mimics, at least in part, an in vitro tumor microenvironment. The results showed that PD alone or in combination with MNC exerts antiproliferative and proapoptotic effects on cancer cells, inhibits the production of the immunosuppressive cytokine IL-10 and of the proinflammatory cytokines upregulated by LPS, and reduces E-selectin and VCAM-1 on endothelial cells. These data provide preclinical support to the hypothesis that PD could be of potential benefit as a therapeutic adjuvant in colon cancer treatment and prevention.

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Section: Introductionmentioning

confidence: 99%

Influence of Polydatin on the Tumor Microenvironment In Vitro: Studies with a Colon Cancer Cell Model

Gregorio

Krasnowska

Zonfrillo

et al. 2022

IJMS

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“…As we all know, TLR4, a member of the toll-like receptor (TLR) family, is involved in innate immunity and mediates inflammatory responses by recognizing LPS or bacterial endotoxins. 56,57 LPS is an important factor in inducing liver damage by activating the TLR4/NF-κB signaling pathway. 5 A lot of studies indicated that LPS exposure induced tissue injury and organ failure.…”

Section: Discussionmentioning

confidence: 99%

“…54 Among the bacteria that changed significantly, Muribaculaceae as a polysaccharide degrading microorganism has been reported to modulate the glucose metabolism and repair the intestinal barrier in highfat diet fed mice. 55,56 Recent studies have shown that gut microbiota can interact with the host by producing metabolites, which are small molecules representing intermediates or end-products of microbial metabolism, and SCFAs or tryptophan metabolites that are able to restore the gut barrier dysfunction in alcohol-fed mice. 54,[57][58][59][60][61] More importantly, ethanol feeding has been shown to cause impaired tryptophan metabolism in the gut, which is the result of ethanol-induced gut microbiota dysbiosis.…”

Section: Papermentioning

confidence: 99%

Fu brick tea alleviates alcoholic liver injury by modulating the gut microbiota–liver axis and inhibiting the hepatic TLR4/NF-κB signaling pathway

Yang

Ren

et al. 2022

Food Funct.

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“…We suggest that XOS interaction with TLR4 has similar effects based on the detected reduction in proinflammatory cytokine production by LPS-stimulated U-937, and this inhibition further contributes to the antitumor activity of the sample. Indeed, another recent study identified the Arg241 residue of TLR4 and the Tyr102, Ser120, and Lys122 residues of MD-2 as the key binding sites of antagonistic ligands [ 52 ]. These data strongly support our results because docking analyses of the XOS-TLR4 and MD-2 interaction showed the ability of xylohexaose to bind at position Tyr102 in MD-2 and strengthen our hypothesis for the inhibitory effect of the XOS sample on TLR4 signaling.…”

Section: Discussionmentioning

confidence: 99%

Natural Xylooligosaccharides Exert Antitumor Activity via Modulation of Cellular Antioxidant State and TLR4

Batsalova

Georgiev

Moten

et al. 2022

IJMS

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It has been recently proven that xylooligosaccharides (XOS) with prebiotic properties have diverse beneficial biological effects including immunomodulatory and antitumor activities. The present article focused on the chemical and biological evaluation of corn-derived commercially available XOS and aimed to elucidate their cytotoxicity and inhibitory potential against tumor cells. Spectrophotometric chemical analyses, Fourier transform infrared spectroscopy, and high-performance liquid chromatography analyses were performed. Antioxidant activity was determined by measuring the oxygen radical absorbance capacity and hydroxyl radical averting capacity. In vitro cytotoxicity assays with human cell lines derived from normal and tumor tissues, assessments of ATP production, mitochondrial membrane potential specific staining, cytokine assays, and molecular docking were used to evaluate the biological activity of XOS. The sample showed significant antioxidant activity, and it was determined that most xylose oligomers in it are composed of six units. XOS exhibited antitumor activity with pronounced inhibitory effect on lysosomes, but mitochondrial functionality was also affected. The production of proinflammatory cytokines by lipopolysaccharide-stimulated U-937 cells was reduced by XOS treatment, which suggested the involvement of Toll-like receptor 4 (TLR4)-mediated signaling in the mechanism of XOS action. Molecular docking analyses confirmed the potential inhibitory interaction between the sample and TLR4. In addition, XOS treatment had significant tumor-cell-specific influence on the glutathione antioxidant system, affecting its balance and thus contributing to the inhibition of cellular viability. The present study elucidated the tumor-inhibitory potential of commercially available XOS that could be utilized in pharmaceutical and food industry providing disease-preventive and therapeutic benefits.

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Toll-like receptor 4 (TLR4) inhibitors: Current research and prospective

Cited by 115 publications

References 123 publications

Influence of Polydatin on the Tumor Microenvironment In Vitro: Studies with a Colon Cancer Cell Model

Influence of Polydatin on the Tumor Microenvironment In Vitro: Studies with a Colon Cancer Cell Model

Fu brick tea alleviates alcoholic liver injury by modulating the gut microbiota–liver axis and inhibiting the hepatic TLR4/NF-κB signaling pathway

Natural Xylooligosaccharides Exert Antitumor Activity via Modulation of Cellular Antioxidant State and TLR4

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