Baicalein ameliorates ulcerative colitis by improving intestinal epithelial barrier via AhR/IL-22 pathway in ILC3s

Cornuside is an iridoid glycoside from Cornus officinalis, with the activities of anti-inflammatory, antioxidant, anti-mitochondrial dysfunction, and neuroprotection. In the present research, a triple-transgenic mice model of AD (3 × Tg-AD) was used to explore the beneficial actions and potential mechanism of cornuside on the memory deficits. We found that cornuside prominently alleviated neuronal injuries, reduced amyloid plaque pathology, inhibited Tau phosphorylation, and repaired synaptic damage. Additionally, cornuside lowered the release of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO), lowered the level of malondialdehyde (MDA), and increased the activity of superoxide dismutase (SOD) and the level of glutathione peroxidase (GSH-Px). Cornuside also significantly reduced the activation of astrocytes and modulated A1/A2 phenotypes by the AKT/Nrf2/NF-κB signaling pathway. We further confirmed that LY294002 and Nrf2 silencing could block the cornuside-mediated phenotypic switch of C6 cells induced by microglia conditioned medium (MCM) in response to lipopolysaccharide (LPS), which indicated that the effects of cornuside in astrocyte activation are dependent on AKT/Nrf2/NF-κB signaling. In conclusion, cornuside may regulate the phenotypic conversion of astrocytes, inhibit neuroinflammation and oxidative stress, improve synaptic plasticity, and alleviate cognitive impairment in mice through the AKT/Nrf2/NF-κB axis. Our present work provides an experimental foundation for further research and development of cornuside as a candidate drug for AD management.

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“…Western blot was conducted following the prior procedure [ 44 , 45 ]. The BCA protein assay kit (Solarbio Science & Technology, Beijing, China.)…”

Section: Methodsmentioning

confidence: 99%

Cornuside Is a Potential Agent against Alzheimer’s Disease via Orchestration of Reactive Astrocytes

et al. 2022

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“…As mentioned previously, 3,4-DAA shares an anthranilic acid core with 3-HAA and 3-HKA, and CH223191 is an antagonist of AhR. 27,33 Therefore, we explored the expression level of AhR in the liver of recipient rats. The expression of AhR and PD-1 in recipient livers was increased and reduced in the 3,4-DAA group and CH223191 group, respectively ( Figure S6E–J , SDC , http://links.lww.com/TP/C449).…”

Section: Resultsmentioning

confidence: 99%

Activation of the Aryl Hydrocarbon Receptor Ameliorates Acute Rejection of Rat Liver Transplantation by Regulating Treg Proliferation and PD-1 Expression

Cao

et al. 2022

Transplantation

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Background. Aryl hydrocarbon receptor (AhR) plays important roles in modulating immune responses. However, the role of AhR in rat liver transplantation (LT) has not been explored. Methods. Safety and side effects of N-(3,4-dimethoxycinnamonyl) anthranilic acid (3,4-DAA) and 2-methyl-2H-pyrazole-3-carboxylic acid amide (CH223191) were evaluated. We used optimal doses of 2 drugs, 3,4-DAA, a drug used for mediating AhR activation, and CH223191, antagonist of AhR (3,4-DAA, CH223191, and 3,4-DAA + CH223191), intraperitoneally administered to recipients daily to investigate the role of AhR in the rat LT model. The recipient livers were used to observe the pathological changes, the cells infiltrating the graft, and changes of AhR and programmed death-1 (PD-1) by Western blot, real-time polymerase chain reaction, and immunofluorescence assays. The contents of Foxp3+ and PD-1+ T cells in the recipient spleen and peripheral blood mononuclear cells were evaluated by flow cytometry. In vitro, after isolating CD4+ T cells, they were treated with different AhR ligands to observe the differentiation direction and PD-1 expression level. Results. The activation of AhR by 3,4-DAA prolonged survival time and ameliorated graft rejection, which were associated with increased expression of AhR and PD-1 in the livers and increased Foxp3+ T cells and PD-1+ T cells in recipient spleens, livers, and peripheral blood mononuclear cells. In vitro, primary T cells incubated with 3,4-DAA mediated increased proportion of Treg and PD-1+ T cells. However, the suppression of AhR with CH223191 reverses these effects, both in the LT model and in vitro. Conclusions. Our results indicated that AhR activation might reduce the occurrence of rat acute rejection by increasing the proportion of Treg and the expression of PD-1.

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“…Although IL-22 can have both pro-inflammatory and anti-inflammatory roles, its pro-inflammatory roles have been studied most extensively, and several studies have shown correlations between IL-22 production and inflammatory skin conditions, uveitis, Alzheimer’s disease, and liver injury [ 7 , 11 , 12 ]. Nonetheless, IL-22 has an anti-inflammatory effect on inflammatory bowel diseases [ 41 , 42 ]. The cell surface-standing IL-22 receptor complex consists of the IL-22Rα and IL-10Rβ receptor chains [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

The Roles of IL-22 and Its Receptor in the Regulation of Inflammatory Responses in the Brain

Lee

et al. 2022

IJMS

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Interleukin (IL)-22 is a potent mediator of inflammatory responses. The IL-22 receptor consists of the IL-22Rα and IL-10Rβ subunits. Previous studies have shown that IL-22Rα expression is restricted to non-hematopoietic cells in the skin, pancreas, intestine, liver, lung, and kidney. Although IL-22 is involved in the development of inflammatory responses, there have been no reports of its role in brain inflammation. Here, we used RT-PCR, Western blotting, flow cytometry, immunohistochemical, and microarray analyses to examine the role of IL-22 and expression of IL-22Rα in the brain, using the microglial cell line, hippocampal neuronal cell line, and inflamed mouse brain tissue. Treatment of BV2 and HT22 cells with recombinant IL-22 increased the expression levels of the pro-inflammatory cytokines IL-6 and TNF-α, as well as cyclooxygenase (COX)-2 and prostaglandin E2. We also found that the JNK and STAT3 signaling pathways play an important role in IL-22-mediated increases in inflammatory mediators. Microarray analyses revealed upregulated expression of inflammation-related genes in IL-22-treated HT22 cells. Finally, we found that IL-22Rα is spontaneously expressed in the brain and is upregulated in inflamed mouse brain. Overall, our results demonstrate that interaction of IL-22 with IL-22Rα plays a role in the development of inflammatory responses in the brain.

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Baicalein ameliorates ulcerative colitis by improving intestinal epithelial barrier via AhR/IL-22 pathway in ILC3s

Cited by 68 publications

References 39 publications

Cornuside Is a Potential Agent against Alzheimer’s Disease via Orchestration of Reactive Astrocytes

Cornuside Is a Potential Agent against Alzheimer’s Disease via Orchestration of Reactive Astrocytes

Activation of the Aryl Hydrocarbon Receptor Ameliorates Acute Rejection of Rat Liver Transplantation by Regulating Treg Proliferation and PD-1 Expression

The Roles of IL-22 and Its Receptor in the Regulation of Inflammatory Responses in the Brain

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