دورية أكاديمية
Nobiletin Attenuates DSS-Induced Intestinal Barrier Damage through the HNF4α-Claudin-7 Signaling Pathway.
| العنوان: | Nobiletin Attenuates DSS-Induced Intestinal Barrier Damage through the HNF4α-Claudin-7 Signaling Pathway. |
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| المؤلفون: | Wen, Xiang, Zhao, Hui, Wang, Liwen, Wang, Liang, Du, Gang, Guan, Wenqiang, Liu, Jianfu, Cao, Xiaocang, Jiang, Xiaohua, Tian, Jingrui, Wang, Meiyan, Ho, Chi-Tang, Li, Shiming |
| المصدر: | Journal of Agricultural and Food Chemistry, 68 (16), 4641 - 4649 (2020-04-22) |
| بيانات النشر: | American Chemical Society (ACS), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | HNF-4α, claudin-7, intestinal epithelial barrier, nobiletin, tangerine peels, Claudins, Cldn7 protein, mouse, Cytokines, Drugs, Chinese Herbal, Flavones, Hepatocyte Nuclear Factor 4, Hnf4a protein, mouse, Tumor Necrosis Factor-alpha, Dextran Sulfate, Animals, Caco-2 Cells, Claudins/genetics, Claudins/metabolism, Colitis/chemically induced, Colitis/drug therapy, Colitis/genetics, Colitis/metabolism, Cytokines/genetics, Cytokines/metabolism, Dextran Sulfate/adverse effects, Disease Models, Animal, Drugs, Chinese Herbal/administration & dosage, Flavones/administration & dosage, Hepatocyte Nuclear Factor 4/genetics, Hepatocyte Nuclear Factor 4/metabolism, Humans, Intestinal Mucosa/drug effects, Intestinal Mucosa/metabolism, Male, Mice, Mice, Inbred C57BL, Signal Transduction/drug effects, Tight Junctions/drug effects, Tight Junctions/metabolism, Tumor Necrosis Factor-alpha/genetics, Tumor Necrosis Factor-alpha/metabolism, General Agricultural and Biological Sciences, General Chemistry, Human health sciences, Gastroenterology & hepatology, Sciences de la santé humaine, Gastroentérologie & hépatologie |
| الوصف: | The intestinal epithelium barrier functions to protect human bodies from damages such as harmful microorganisms, antigens, and toxins. In this study, we evaluated the protective effect and molecular mechanism of a dominant polymethoxyflavone nobiletin (NOB) from tangerine peels on intestinal epithelial integrity. The results from transepithelial electrical resistance (TEER) suggested that NOB pretreatment counteracts epithelial injury induced by inflammatory cytokines (TEER value in 48 h: vehicle, 135.6 ± 3.9 Ω/cm2; TNF-α + IL-1β, 90.7 ± 0.5 Ω/cm2; 10 μM NOB + TNF-α + IL-1β, 126.1 ± 0.8 Ω/cm2; 100 μM NOB + TNF-α + IL-1β, 125.3 ± 0.5 Ω/cm2. P < 0.001). Clinical and pathological test results suggested that administration of NOB effectively alleviates intestinal barrier injury induced by dextran sulfate sodium (DSS) as evidenced by the length of colon villi on day 7 (control, 253.7 ± 4.8 μm, DSS 131.6 ± 4.6 μm, NOB + DSS, 234.5 ± 5.1 μm. P < 0.001). Interestingly, when screening tight junction molecules for intestinal barrier integrity, we observed that independent treatment with NOB sharply increased claudin-7 levels (ratio of claudin-7 over GAPDH: control, 1.0 ± 0.06; DSS, 0.02 ± 0.001; NOB + DSS, 0.3 ± 0.07. P < 0.001), which was previously suppressed upon DSS stimulation. Furthermore, hepatocyte nuclear factor 4α (HNF-4α) transcriptional regulation of claudin-7 contributed to intestinal barrier homeostasis. Therefore, our study suggests potential intestinal protective strategies based on polymethoxyflavones of aged tangerine peels. |
| نوع الوثيقة: | journal article http://purl.org/coar/resource_type/c_6501 article peer reviewed |
| اللغة: | English |
| Relation: | https://pubs.acs.org/doi/pdf/10.1021/acs.jafc.0c01217; urn:issn:0021-8561; urn:issn:1520-5118 |
| DOI: | 10.1021/acs.jafc.0c01217 |
| URL الوصول: | https://orbi.uliege.be/handle/2268/316052 |
| حقوق: | open access http://purl.org/coar/access_right/c_abf2 info:eu-repo/semantics/openAccess |
| رقم الأكسشن: | edsorb.316052 |
| قاعدة البيانات: | ORBi |
| DOI: | 10.1021/acs.jafc.0c01217 |
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