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Objective: To investigate the effects of Astragaloside IV (AS-IV) on intestinal barrier function in mice with ulcerative colitis (UC) and to explore its underlying mechanisms. Methods: The UC mouse model was established using 3% dextran sulfate sodium (DSS). Upon successful model establishment, the animals were divided into control, DSS model, and AS-IV treatment groups (10, 20 and 40 mg/kg). All treatments were administered via oral gavage once daily for 10 days. The protein expression levels of the AhR/IL-22 pathway were analyzed by Western blotting. Fluorescence in situ hybridization (FISH) was performed to examine DAPI staining patterns in colon tissue sections. Apoptosis rates were measured by flow cytometry, and transcriptional levels of AHR, CYP1A1, and IL-22 were evaluated using qRT-PCR. Results: AS-IV ameliorated intestinal inflammation, reduced intestinal permeability, and promoted the restoration of colonic tight junction structures in colitis mice, potentially through activation of the AhR/IL-22 pathway. The therapeutic effects of AS-IV were partially attenuated by the AhR antagonist CH223191, whereas the AhR agonist FICZ exhibited comparable protective effects on colitis symptoms and intestinal barrier function. In vitro mechanistic investigations demonstrated that AS-IV treatment significantly upregulated the expression of CYP1A1 (P<0.01), a downstream target protein of AhR, in MNK-3 cells. Furthermore, AS-IV markedly enhanced IL-22 secretion (P<0.01) by facilitating AhR nuclear translocation. Notably, these regulatory effects were substantially diminished in AhR-silenced MNK-3 cells (shAhR-MNK3) (P>0.05), conclusively establishing that AS-IV modulates IL-22 production through an AhR-dependent mechanism. Conclusion: AS-IV ameliorated UC by activating the AhR/IL-22 pathway in ILC3 cells, thereby restoring intestinal barrier function. These findings highlight AS-IV as a potential therapeutic candidate for UC treatment.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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