[en] 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.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Wen, Xiang ; Université de Liège - ULiège > GIGA > GIGA Stem Cells - Medical Chemistry ; Tianjin Key Laboratory of Food and Biotechnology, State Experimental and Training Centre of Food and Drug, School of Biotechnology and Food Science, Tianjin University of Commerce, No. 409 Guangrong Road, Beichen, Tianjin 300134, China
Zhao, Hui ; Tianjin Key Laboratory of Food and Biotechnology, State Experimental and Training Centre of Food and Drug, School of Biotechnology and Food Science, Tianjin University of Commerce, No. 409 Guangrong Road, Beichen, Tianjin 300134, China
Wang, Liwen; Tianjin Key Laboratory of Food and Biotechnology, State Experimental and Training Centre of Food and Drug, School of Biotechnology and Food Science, Tianjin University of Commerce, No. 409 Guangrong Road, Beichen, Tianjin 300134, China
Wang, Liang; Tianjin Key Laboratory of Food and Biotechnology, State Experimental and Training Centre of Food and Drug, School of Biotechnology and Food Science, Tianjin University of Commerce, No. 409 Guangrong Road, Beichen, Tianjin 300134, China
Du, Gang; Tianjin Key Laboratory of Food and Biotechnology, State Experimental and Training Centre of Food and Drug, School of Biotechnology and Food Science, Tianjin University of Commerce, No. 409 Guangrong Road, Beichen, Tianjin 300134, China
Guan, Wenqiang; Tianjin Key Laboratory of Food and Biotechnology, State Experimental and Training Centre of Food and Drug, School of Biotechnology and Food Science, Tianjin University of Commerce, No. 409 Guangrong Road, Beichen, Tianjin 300134, China
Liu, Jianfu; Tianjin Key Laboratory of Food and Biotechnology, State Experimental and Training Centre of Food and Drug, School of Biotechnology and Food Science, Tianjin University of Commerce, No. 409 Guangrong Road, Beichen, Tianjin 300134, China
Cao, Xiaocang; Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, No. 154 Anshan Road, Heping, Tianjin 300020, China
Jiang, Xiaohua; Department of Histlolgy and Embrylolgy, School of Basic Medicine, North China University of Science and Technology, 21 Bohai Road, Caofeidian Xincheng, Tangshan, Hebei 063210, China
Tian, Jingrui; Department of Histlolgy and Embrylolgy, School of Basic Medicine, North China University of Science and Technology, 21 Bohai Road, Caofeidian Xincheng, Tangshan, Hebei 063210, China
Wang, Meiyan ; Tianjin Key Laboratory of Food and Biotechnology, State Experimental and Training Centre of Food and Drug, School of Biotechnology and Food Science, Tianjin University of Commerce, No. 409 Guangrong Road, Beichen, Tianjin 300134, China
Ho, Chi-Tang; Department of Food Science, Rutgers University, New Brunswick, New Jersey 07102, United States
Li, Shiming; Hubei Key Laboratory of EFGIR, Huanggang Normal University, Huanggang, Hubei 438000, China ; Department of Food Science, Rutgers University, New Brunswick, New Jersey 07102, United States
NSCF - National Natural Science Foundation of China
Funding text :
This study was supported by the National Natural Science Foundation of China (grant nos. 31571832, 31772019, and 81803548), Tianjin Innovative Research Team grant (TD13-5087), Natural Science Foundation of Tianjin (19JCQNJC12400), Open Project of Tianjin Key Laboratory of Food Biotechnology (TJCU-KLFB-18201), and College Student Innovation and Entrepreneurship Training (201910069164).
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