PT  - JOURNAL ARTICLE
AU  - Zhang, Jingjing
AU  - Ding, Lili
AU  - Wang, Baocan
AU  - Ren, Gaiyan
AU  - Sun, Aning
AU  - Deng, Chao
AU  - Wei, Xiaohui
AU  - Mani, Sridhar
AU  - Wang, Zhengtao
AU  - Dou, Wei
TI  - Notoginsenoside R1 Attenuates Experimental Inflammatory Bowel Disease via Pregnane X Receptor Activation
AID  - 10.1124/jpet.114.218750
DP  - 2015 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 315--324
VI  - 352
IP  - 2
4099  - http://jpet.aspetjournals.org/content/352/2/315.short
4100  - http://jpet.aspetjournals.org/content/352/2/315.full
SO  - J Pharmacol Exp Ther2015 Feb 01; 352
AB  - Notoginsenoside R1 (R1) is the main bioactive component in Panax notoginseng, an old herb medicine widely used in Asian countries in the treatment of microcirculatory diseases. However, little is known about the effect of R1 on inflammatory bowel disease (IBD). The present study demonstrated that R1 alleviated the severity of dextran sulfate sodium–induced colitis in mice by decreasing the activity of myeloperoxidase, the production of cytokines, the expression of proinflammatory genes, and the phosphorylation of IκB kinase, IκBα, and p65 in the colon. Further studies indicated that R1 dose-dependently activated human/mouse pregnane X receptor (PXR), a known target for decreasing inflammation in IBD, and upregulated the expression of genes involved in xenobiotic metabolism in colorectal cells and the colon. Ligand pocket–filling mutant (S247W/C284W or S247W/C284W/S208W) of the human PXR abrogated the effect of R1 on PXR activation. Time-resolved fluorescence resonance energy transfer PXR competitive binding assay confirmed R1 (ligand) binding affinity. In addition, PXR overexpression inhibited nuclear factor-κB (NF-κB)–luciferase activity, which was potentiated by R1 treatment. PXR knockdown by small interfering RNA demonstrated the necessity of PXR in R1-induced upregulation of the expression of xenobiotic-metabolizing enzymes and downregulation of NF-κB activity. Finally, the anti-inflammatory effect of R1 was confirmed in trinitrobenzene sulfonic acid–induced colitis in mice. These findings suggest that R1 attenuates experimental IBD possibly via the activation of intestinal PXR signaling.