Journal
FRONTIERS IN PHARMACOLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.1000444
Keywords
ulcerative colitis; inflammatory bowel disease; inflammation; ginsenoside Rc; intestinal barriers
Categories
Funding
- Key projects of Guangdong Provincial Department of Education
- Basic and Applied Basic Research Foundation of Guangdong Province Regional Joint Fund Project [2021ZDZX 2010]
- Discipline Construction Project of Guangdong Medical University [2020B1515120021]
- Zhanjiang City science and technology development special fund competitive allocation project [4SG21276P, 1003K20220004]
- TCM Scientific Research Project of Guangdong Provincial Bureau of Traditional Chinese Medicine [2018A01029]
- Characteristic Innovation Project of Guangdong Province General University [20211215]
- Dongguan City Science and Technology Correspondent Project [2020KTSCX042, 2019KTSCX046]
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The study demonstrates that ginsenoside Rc can alleviate inflammation and barrier function deficiencies by activating FXR signaling, thereby protecting the intestines from damage induced by dextran sulfate sodium (DSS).
Objectives: Farnesoid X receptor (FXR) activation is involved in ameliorating inflammatory bowel disease (IBD), such as ulcerative colitis (UC), and inflammatory regulation may be involved in its mechanism. Ginsenoside Rc (Rc) is a major component of Panax ginseng, and it plays an excellent role in the anti-inflammatory processes. Our aim is to explore the alleviative effect of Rc on dextran sulfate sodium (DSS)-induced inflammation and deficiencies in barrier function based on FXR signaling.Materials and Methods: In vitro, we treated human intestinal epithelial cell lines (LS174T) with LPS to explore the anti-inflammatory effect of Rc supplementation. In vivo, a DSS-induced IBD mice model was established, and the changes in inflammatory and barrier function in colons after Rc treatment were measured using the disease activity index (DAI), hematoxylin and eosin (H & E) staining, immunofluorescence, ELISA, and qPCR. Molecular docking analysis, luciferase reporter gene assay, and qPCR were then used to analyze the binding targets of Rc. DSS-induced FXR-knockout (FXR-/-) mice were used for further validation.Results: Rc significantly recovered the abnormal levels of inflammation indexes (TNF-alpha, IL-6, IL-1 beta, and NF-KB) induced by LPS in LS174T. DSS-induced C57BL/6 mice exhibited a significantly decreased body weight and elevated DAI, as well as a decrease in colon weight and length. Increased inflammatory markers (TNF-alpha, IL-6, IL-1 beta, ICAM1, NF-KB, F4/80, and CD11b displayed an increased expression) and damaged barrier function (Claudin-1, occludin, and ZO-1 displayed a decreased expression) were observed in DSS-induced C57BL/6 mice. Nevertheless, supplementation with Rc mitigated the increased inflammatory and damaged barrier function associated with DSS. Further evaluation revealed an activation of FXR signaling in Rc-treated LS174T, with FXR, BSEP, and SHP found to be upregulated. Furthermore, molecular docking indicated that there is a clear interaction between Rc and FXR, while Rc activated transcriptional expression of FXR in luciferase reporter gene assay. However, these reversal abilities of Rc were not observed in DSS-induced FXR-/- mice.Conclusion: Our findings suggest that Rc may ameliorate inflammation and barrier function in the intestine, which in turn leads to the attenuation of DSS-induced UC, in which Rc may potentially activate FXR signaling to protect the intestines from DSS-induced injury.
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