biostudies-literatureYan TIntramural NIH HHSe21968https://www.ebi.ac.uk/biostudies/studies/S-EPMC10167919biostudies-literatureUnknown35(11)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 translocationFASEB journal : official publication of the Federation of American Societies for Experimental BiologySt. John's Wort alleviates dextran sodium sulfate-induced colitis through pregnane X receptor-dependent NFκB antagonism.PMC10167919ZIA BC005562Xia YHamada KWang PWang QYan NKrausz KWYan TLuo YHao HGonzalez FJWard JMfalseSt. John's Wort alleviates dextran sodium sulfate-induced colitis through pregnane X receptor-dependent NFκB antagonism.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 translocation2021-01-01T00:00:00Z2021 Nov2025-04-05T09:10:20.293Z2025-04-05T09:10:20.293ZS-EPMC101679193464442610.1096/fj.202001098R10.1096/fj.202001098r