St. John's Wort alleviates dextran sodium sulfate‐induced colitis through pregnane X receptor‐dependent NFκB antagonism. Issue 11 (13th October 2021)

• Record Type: Journal Article
• Authors: Yan, Tingting; Luo, Yuhong; Xia, Yangliu; Hamada, Keisuke; Wang, Qiong; Yan, Nana; Krausz, Kristopher W.; Ward, Jerrold M.; Hao, Haiping; Wang, Ping; Gonzalez, Frank J.
• Is Part Of: FASEB journal. Volume 35:Issue 11(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-10-13
• Subjects: DSS -- IBD -- natural products -- NFκB -- PXR -- small intestine; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202001098R
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: St. John's wort (SJW), from traditional herbs, activates the pregnane X receptor (PXR), a potential drug target for treating inflammatory bowel disease (IBD). However, how SJW alleviates dextran sodium sulfate (DSS)‐induced experimental IBD by activating PXR is unknown. To test this, PXR ‐humanized, wild‐type (WT) and Pxr ‐null mice, primary intestinal organoids cultures, and the luciferase reporter gene assays were employed. In vivo, a diet supplemented with SJW was found to activate intestinal PXR both in WT and PXR ‐humanized mice, but not in Pxr ‐null mice. SJW prevented DSS‐induced IBD in PXR ‐humanized and WT mice, but not in Pxr ‐null mice. In vitro, hyperforin, a major component of SJW, activated PXR and suppressed tumor necrosis factor (TNF)α‐induced nuclear factor (NF) κB translocation in primary intestinal organoids from PXR ‐humanized mice, but not Pxr ‐null mice. Luciferase reporter gene assays showed that hyperforin dose‐dependently alleviated TNFα‐induced NFκB transactivation by activating human PXR in Caco2 cells. Furthermore, SJW therapeutically attenuated DSS‐induced IBD in PXR ‐humanized mice. These data indicate the therapeutic potential of SJW in alleviating DSS‐induced IBD in vivo, and TNFα‐induced NFκB activation in vitro, dependent on PXR activation, which may have clinical implications for using SJW as a herbal drug anti‐IBD treatment.