Nobiletin Attenuates DSS-Induced Intestinal Barrier Damage through the HNF4a-Claudin-7 Signaling Pathway

Xiang Wen, Hui Zhao, Liwen Wang, Liang Wang, Gang Du, Wenqiang Guan, Jianfu Liu, Xiaocang Cao, Xiaohua Jiang, Jingrui Tian, Meiyan Wang, Chi Tang Ho, Shiming Li

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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 ?/cm2 TNF-a + IL-1ß, 90.7 ± 0.5 ?/cm2 10 µM NOB + TNF-a + IL-1ß, 126.1 ± 0.8 ?/cm2 100 µM NOB + TNF-a + IL-1ß, 125.3 ± 0.5 ?/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 4a (HNF-4a) 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.

Original languageEnglish (US)
Pages (from-to)4641-4649
Number of pages9
JournalJournal of agricultural and food chemistry
Volume68
Issue number16
DOIs
StatePublished - Apr 22 2020

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

Keywords

  • HNF-4a
  • claudin-7
  • intestinal epithelial barrier
  • nobiletin
  • tangerine peels

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