Indole-3-aldehyde alleviates chondrocytes inflammation through the AhR-NF-κB signalling pathway

Zhuang, Huangming; Li, Bin; Xie, Ting; Xu, Changgeng; Ren, Xunshan; Jiang, Fuze; Lei, Tiechi; Zhou, Panghu

doi:10.1016/j.intimp.2022.109314

Cited by 17 publications

(9 citation statements)

References 36 publications

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“…Activation of aryl hydrocarbon receptors (AhR) in the intestine promotes the secretion of IL-22 by intestinal epithelial cells and the growth of epithelial cells in the intestine, thus maintaining intestinal health [13]. Metabolite 3-Indolealdehyde (3-IAld) is a common tryptophan metabolite in the intestinal tract and has significant anti-inflammatory effects by activating AhR receptors, such as reducing chondrocyte inflammation by modulating the AhR-NF-κB signaling pathway [14], and it has also been shown to restore the integrity of the intestinal mucosa [15]. However, the exact mechanism by which 3-IAld treats UC remains unclear.…”

Section: Introductionmentioning

confidence: 99%

The Tryptophan Metabolite Indole-3-Carboxaldehyde Alleviates Mice with DSS-Induced Ulcerative Colitis by Balancing Amino Acid Metabolism, Inhibiting Intestinal Inflammation, and Improving Intestinal Barrier Function

et al. 2023

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Ulcerative colitis (UC) has attracted much attention for its negative influence on quality of life and increased risk of colorectal cancer. Chemical and biological drugs are currently the usual treatment for UC. These drugs always induce severe side effects, or patients might become resistant to these therapies. Therefore, new therapeutic options for UC are urgently needed. In this study, we discovered the inhibitory activity of the intestinal tryptophan metabolite indole-3-carboxaldehyde (3-IAld) in dextran sulfate sodium salt (DSS)-induced UC mice by targeting the TLR4/NF-κB/p38 signaling pathway. This compound effectively protected against colon length shortening and damage induced by DSS in the colon, notably reducing the severity of inflammation. The production of inflammatory factors of TNF-α, IL-6, and IL-1β was significantly attenuated when treating with 3-IAld in vivo and vitro. This might be attributed to inhibition of the TLR4/NF-kB/p38 signaling pathway. Moreover, 3-IAld could up-regulate the expression of ZO-1 and Occludin in vivo and vitro. Meanwhile, liquid chromatography mass spectrometry (LC-MS) results showed that 3-IAld could balance the aspartate and glutamate metabolism and the lysine degradation metabolism in the serum of DSS-induced colitis mice. In conclusion, 3-IAld ameliorated the intestinal barrier dysfunction and inflammatory response in DSS-induced UC mice, balanced amino acid metabolism, and inhibited the activation of the TLR4/NF-kB/p38 signaling pathway, thereby protecting mice with colitis.

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Section: Introductionmentioning

confidence: 99%

The Tryptophan Metabolite Indole-3-Carboxaldehyde Alleviates Mice with DSS-Induced Ulcerative Colitis by Balancing Amino Acid Metabolism, Inhibiting Intestinal Inflammation, and Improving Intestinal Barrier Function

et al. 2023

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“…These intestinal microbiota-derived tryptophan metabolites play a vital role in maintaining gut homeostasis, as well as attenuating inflammatory-related diseases ( Su et al, 2022 ). I3A can restore mucosal integrity and inhibit inflammation by regulating intestinal microbiome ( D’Onofrio et al, 2021 ; Zhuang et al, 2022 ). ILA significantly reduced LPS-induced macrophage inflammatory response and oxidative stress response, and is elevated in infant feces, showing protective effect on intestinal epithelial cells ( Ehrlich et al, 2020 ; Meng et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

Unlocking the potential of Rosa roxburghii Tratt polyphenol: a novel approach to treating acute lung injury from a perspective of the lung-gut axis

Tang,

Zhang,

Zhang

et al. 2024

Front. Microbiol.

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IntroductionAcute lung injury (ALI) is a serious respiratory disease characterized by progressive respiratory failure with high morbidity and mortality. It is becoming increasingly important to develop functional foods from polyphenol-rich medicinal and dietary plants in order to prevent or alleviate ALI by regulating intestinal microflora. Rosa roxburghii Tratt polyphenol (RRTP) has significant preventive and therapeutic effects on lipopolysaccharide-induced ALI mice, but its regulatory effects on gut homeostasis in ALI mice remains unclear.MethodsThis study aims to systematically evaluate the ameliorative effects of RRTP from the perspective of “lung-gut axis” on ALI mice by intestine histopathological assessment, oxidative stress indicators detection and short-chain fatty acids (SCFAs) production, and then explore the modulatory mechanisms of RRTP on intestinal homeostasis by metabolomics and gut microbiomics of cecal contents.ResultsThe results showed that RRTP can synergistically exert anti-ALI efficacy by significantly ameliorating intestinal tissue damage, inhibiting oxidative stress, increasing SCFAs in cecal contents, regulating the composition and structure of intestinal flora, increasing Akkermansia muciniphila and modulating disordered intestinal endogenous metabolites.DiscussionThis study demonstrated that RRTP has significant advantages in adjuvant therapy of ALI, and systematically clarified its comprehensive improvement mechanism from a new perspective of “lung-gut axis”, which provides a breakthrough for the food and healthcare industries to develop products from botanical functional herbs and foods to prevent or alleviate ALI by regulating intestinal flora.

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“…Furthermore, it has been shown that the activation of the AhR pathway can inhibit the NF-κB pathway, which plays a crucial role in enhancing intestinal barrier function and attenuating the inflammatory response. 13,46 It was found that ligand-activated AhR can block NF-κB transcription, negatively regulate NLRP3 inflammasome expression in peritoneal macrophages, inhibit caspase-1 activation, and the secretion of IL-1β. 47 The NF-κB pathway activation contributes to the secretion of a large number of inflammatory factors, among which high concentrations of TNF-α and IL-6 will cause intestinal inflammation and intestinal barrier damage.…”

Section: ■ Discussionmentioning

confidence: 99%

“…This suggested that S164 and its Trp metabolite could activate the AhR–Nrf2 pathway through a two-pronged mechanism, thus improving intestinal barrier function in vivo . Furthermore, it has been shown that the activation of the AhR pathway can inhibit the NF-κB pathway, which plays a crucial role in enhancing intestinal barrier function and attenuating the inflammatory response. , It was found that ligand-activated AhR can block NF-κB transcription, negatively regulate NLRP3 inflammasome expression in peritoneal macrophages, inhibit caspase-1 activation, and the secretion of IL-1β . The NF-κB pathway activation contributes to the secretion of a large number of inflammatory factors, among which high concentrations of TNF-α and IL-6 will cause intestinal inflammation and intestinal barrier damage. − Niu et al found that Lactobacillus rhamnosus MN-431 Trp broth activated ileal and colonic PXR–NF-κB signaling, reduced the inflammatory factor expression, especially TNF-α, and attenuated intestinal mucosal injury in rats .…”

Section: Discussionmentioning

confidence: 99%

Lactiplantibacillus plantarum-Derived Indole-3-lactic Acid Ameliorates Intestinal Barrier Integrity through the AhR/Nrf2/NF-κB Axis

Wang,

Guan,

Wang

et al. 2024

J. Agric. Food Chem.

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Our previous studies have shown that Lactiplantibacillus plantarum DPUL-S164-derived indole-3-lactic acid (ILA) ameliorates intestinal epithelial cell barrier injury by activating aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2related factor 2 (Nrf2) signaling pathways and promoting tight junction protein expression. This study further explored the crucial substances of L. plantarum DPUL-S164 in alleviating intestinal barrier damage in mice through a dextran sodium sulfate-induced ulcerative colitis mouse model. Compared to dead L. plantarum DPUL-S164 (D-S164), live L. plantarum DPUL-S164 (S164) and its tryptophan metabolite, ILA, showed an effective ameliorating effect on the intestinal barrier injury of mice treated by antibiotic cocktail and sodium dextran sulfate, suggesting that the crucial substances of L. plantarum DPUL-S164 ameliorating intestinal barrier injury are its extracellular metabolites. Furthermore, S164 and its tryptophan metabolite, ILA, ameliorate intestinal barrier injury and suppress intestinal inflammation by activating the AhR−Nrf2 pathway and inhibiting the nuclear factor kappa-B (NF-κB) pathway. These results suggest that L. plantarum DPUL-S164 ameliorates intestinal epithelial barrier damage in mice, primarily by producing ILA as a ligand to activate the AhR pathway.

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Indole-3-aldehyde alleviates chondrocytes inflammation through the AhR-NF-κB signalling pathway

Cited by 17 publications

References 36 publications

The Tryptophan Metabolite Indole-3-Carboxaldehyde Alleviates Mice with DSS-Induced Ulcerative Colitis by Balancing Amino Acid Metabolism, Inhibiting Intestinal Inflammation, and Improving Intestinal Barrier Function

The Tryptophan Metabolite Indole-3-Carboxaldehyde Alleviates Mice with DSS-Induced Ulcerative Colitis by Balancing Amino Acid Metabolism, Inhibiting Intestinal Inflammation, and Improving Intestinal Barrier Function

Unlocking the potential of Rosa roxburghii Tratt polyphenol: a novel approach to treating acute lung injury from a perspective of the lung-gut axis

Lactiplantibacillus plantarum-Derived Indole-3-lactic Acid Ameliorates Intestinal Barrier Integrity through the AhR/Nrf2/NF-κB Axis

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