Soy isoflavones ameliorate experimental colitis by targeting ERα/NLRP3 inflammasome pathways

Gao, Xiaona; Fan, Wentao; Tan, Lei; Shi, Yuanguo; Ding, Chenchen; Liu, Shuhui; Miao, Yufan; Luo, Yan; Shi, Xizhi; DeSaeger, Sarah; Song, Suquan

doi:10.1016/j.jnutbio.2020.108438

Cited by 17 publications

(15 citation statements)

References 37 publications

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“…Soy isoflavones represent an interesting flavonoid choice for the treatment of many inflammation disorders. A recent study conducted on dextran sodium sulphate (DSS)-treated mice reported the inhibiting capacity of soy isoflavones on NLRP3 inflammasome complex expression, reducing the NLRP3, caspase-1 p20, and ASC protein levels and suppressing the release of IL-1β and IL-18 [ 91 ].…”

Section: Food Components As Nlpr3 Modulatorsmentioning

confidence: 99%

Modulatory Properties of Food and Nutraceutical Components Targeting NLRP3 Inflammasome Activation

et al. 2022

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Inflammasomes are key intracellular multimeric proteins able to initiate the cellular inflammatory signaling pathway. NLRP3 inflammasome represents one of the main protein complexes involved in the development of inflammatory events, and its activity has been largely demonstrated to be connected with inflammatory or autoinflammatory disorders, including diabetes, gouty arthritis, liver fibrosis, Alzheimer’s disease, respiratory syndromes, atherosclerosis, and cancer initiation. In recent years, it has been demonstrated how dietary intake and nutritional status represent important environmental elements that can modulate metabolic inflammation, since food matrices are an important source of several bioactive compounds. In this review, an updated status of knowledge regarding food bioactive compounds as NLRP3 inflammasome modulators is discussed. Several chemical classes, namely polyphenols, organosulfurs, terpenes, fatty acids, proteins, amino acids, saponins, sterols, polysaccharides, carotenoids, vitamins, and probiotics, have been shown to possess NLRP3 inflammasome-modulating activity through in vitro and in vivo assays, mainly demonstrating an anti-NLRP3 inflammasome activity. Plant foods are particularly rich in important bioactive compounds, each of them can have different effects on the pathway of inflammatory response, confirming the importance of the nutritional pattern (food model) as a whole rather than any single nutrient or functional compound.

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Section: Food Components As Nlpr3 Modulatorsmentioning

confidence: 99%

Modulatory Properties of Food and Nutraceutical Components Targeting NLRP3 Inflammasome Activation

et al. 2022

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“…CAC is a progressive process from inflammation to cancer, so the prevention of CAC is of vital importance. At present, one of the most prevalent treatments for IBD in clinical is administration of some agents, including 5-aminosalicylic acid, corticosteroids, biological agents and immunosuppressants (Gao et al, 2020). However, treatment with these drugs tends to increase the patient's susceptibility to infection and leads to different adverse drug reactions (Gong et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Amelioration of AOM/DSS-Induced Murine Colitis-Associated Cancer by Evodiamine Intervention is Primarily Associated with Gut Microbiota-Metabolism-Inflammatory Signaling Axis

et al. 2021

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Evodiamine (EVO), an indole alkaloid derived from Rutaceae plants Evodia rutaecarpa (Juss.) Benth.、Evodia rutaecarpa (Juss.) Benth. Var. bodinieri (Dode) Huang or Evodia rutaecarpa (Juss.) Benth. Var. officinalis (Dode) Huang, has anti-inflammatory and anti-tumor activities. Our previous study found that EVO attenuates colitis by regulating gut microbiota and metabolites. However, little is known about its effect on colitis-associated cancer (CAC). In this study, the protective effects of EVO on azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis and tumor mice were observed, and the underlying potential mechanism was clarified. The results suggested that EVO ameliorated AOM/DSS-induced colitis by inhibiting the intestinal inflammation and improving mucosal barrier function. And EVO significantly reduced the number and size of AOM/DSS-induced colorectal tumors along with promoted apoptosis and inhibited proliferation of epithelial cell. Moreover, EVO promoted the enrichment of SCFAs-producing bacteria and reduced the levels of the pro-inflammatory bacteria, which contributes to the changes of microbiota metabolism, especially tryptophan metabolism. Furthermore, inflammatory response (like Wnt signaling pathway、Hippo signaling pathway and IL-17 signaling pathway) were effectively alleviated by EVO. Our study demonstrated that the protective therapeutic action of EVO on CAC is to inhibit the development of intestinal inflammation-cancer by regulating gut microbiota metabolites and signaling pathways of colon intestinal epithelial, which may represent a novel agent for colon cancer prevention via manipulation of gut microbiota.

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“…Moreover, they can inhibit the expression of NLRP3, HSCs activation, and liver fibrosis by acting on different estrogen ligands. Soybean isoflavones can alleviate DSS-induced colitis by inhibiting the ERα pathway and downregulating the subsequent activation of the NLRP3 inflammasome ( Gao et al, 2020 ). Phytoestrogen calycosin inhibits the activation, proliferation, and migration of HSCs induced by TGF-β1 via downregulating ERβ ( Deng et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…Research on the anti-fibrosis effects of estrogen confirmed that ERs are expressed in hepatocytes, sinusoidal endothelial cells, Kupffer cells and stellate cells, and that estrogen can improve the microcirculation of damaged liver, inhibit the proliferation of activated HSCs and the synthesis of collagen, promote the activity of antioxidant enzyme GPx in hepatocytes, prevent lipid peroxidation, regulate the expression of cytokines such as transforming growth factor, and inhibit the occurrence and development of liver fibrosis ( Zhang et al, 2016 ; Lee et al, 2019 ). Studies have shown that the inhibition of NLRP3 inflammasome depends on the blockade of ERα in colitis ( Gao et al, 2020 ). Zhang et al demonstrated that estrogen exerted its anti-fibrosis effects via ERβ rather than ERα or GPER ( Zhang et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Saikosaponin d Alleviates Liver Fibrosis by Negatively Regulating the ROS/NLRP3 Inflammasome Through Activating the ERβ Pathway

Zhang

Lei²,

Zhu³

et al. 2022

Front. Pharmacol.

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Background and aims: Saikosaponin d (SSd) has a steroidal structure and significant anti-inflammatory effects. The purpose of this study was to explore the mechanism underlying SSd’s inhibitory effects on liver fibrosis.Methods: Wild-type and estrogen receptor knockout (ERKO) mice were treated with CCl4 to establish liver fibrosis mouse models. The effects of SSd on hepatic fibrogenesis were studied in these mouse models. Hepatic stellate cells (HSCs) were activated by H2O2 to investigate the potential molecular mechanisms. The establishment of the models and the degrees of inflammation and liver tissue fibrosis were evaluated by detecting changes in serum liver enzymes and liver histopathology. The expression of α-SMA and TGF-β1 was determined by immunohistochemistry. The expression and significance of NLRP3 inflammasome proteins were explored by RT-PCR and Western blotting analyses. The mitochondrial ROS-related indexes were evaluated by MitoSOX Red.Results: In wild-type and ERKO mice treated with CCl4, the fluorescence expression of mitochondrial ROS was up-regulated, while the mitochondrial membrane potential and ATP content were decreased, suggesting that the mitochondria were damaged. In addition, the expression of NLRP3 inflammatory bodies and fibrosis markers (α-SMA, TGF-β, TIMP-1, MMP-2, and Vimentin) in liver tissue increased. Furthermore, the above indexes showed the same expression trend in activated HSCs. In addition, the peripheral serum ALT and AST levels increased in CCl4-induced liver injury model mice. And HE staining showed a large number of inflammatory cell infiltration in the liver of model mice. Picric acid-Sirius staining and Masson staining showed that there was significant collagen fibrous tissue deposition in mice liver sections. IHC and WB detection confirmed that the expression of α-SMA and TGF-β1 increased. Liver fibrosis scores were also elevated. Then, after SSd intervention, the expression of ROS in wild-type mice and αERKO mice decreased, mitochondrial membrane potential recovered, ATP level increased, NLRP3 inflammasome and fibrosis indexes decreased, liver enzyme levels decreased, and liver pathology showed liver inflammation. The damage and collagen deposition were significantly relieved, the expression of α-SMA and TGF-β1 was decreased, and the fibrosis score was also decreased. More importantly, the effect of SSd in alleviating liver injury and liver fibrosis had no effect on βERKO mice.Conclusion: SSd alleviated liver fibrosis by negatively regulating the ROS/NLRP3 inflammasome through activating the ERβ pathway. By establishing liver fibrosis models using wild-type and ERKO mice, we demonstrated that SSd could alleviate liver fibrosis by inhibiting the ROS/NLRP3 inflammasome axis through activating the ERβ pathway.

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Soy isoflavones ameliorate experimental colitis by targeting ERα/NLRP3 inflammasome pathways

Cited by 17 publications

References 37 publications

Modulatory Properties of Food and Nutraceutical Components Targeting NLRP3 Inflammasome Activation

Modulatory Properties of Food and Nutraceutical Components Targeting NLRP3 Inflammasome Activation

Amelioration of AOM/DSS-Induced Murine Colitis-Associated Cancer by Evodiamine Intervention is Primarily Associated with Gut Microbiota-Metabolism-Inflammatory Signaling Axis

Saikosaponin d Alleviates Liver Fibrosis by Negatively Regulating the ROS/NLRP3 Inflammasome Through Activating the ERβ Pathway

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