ArticleThe Journal of nutritional biochemistry2014
Plant flavonol isorhamnetin attenuates chemically induced inflammatory bowel disease via a PXR-dependent pathway.
Article in The Journal of nutritional biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 86 citations in OpenAlex.
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- Integrated multi-omics analysis reveals a gut microbiota-tryptophan metabolism axis contributes to sex differences in a β-aminopropionitrile-induced aortic dissection mouse model.Biology of sex differences · 2026Article
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- Gastrodin Attenuates Colitis and Prevents Tumorigenesis in Mice by Interrupting TLR4/MD2/NF-κB Signaling Transduction.Anti-cancer agents in medicinal chemistry · 2024Article
- Harnessing the Anti-Inflammatory Properties of Polyphenols in the Treatment of Inflammatory Bowel Disease.International journal of biological sciences · 2024Review
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- Advances in natural compound-based nanomedicine and the interaction with gut microbiota in ulcerative colitis therapy.Frontiers in pharmacology · 2023Review
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- Pregnane X Receptor and the Gut-Liver Axis: A Recent Update.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- In Silico and In Vitro Identification of Pan-Coronaviral Main Protease Inhibitors from a Large Natural Product Library.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Understanding the physiological functions of the host xenobiotic-sensing nuclear receptors PXR and CAR on the gut microbiome using genetically modified mice.Acta pharmaceutica Sinica. B · 2022Article
- Effects of Isorhamnetin on Diabetes and Its Associated Complications: A Review of In Vitro and In Vivo Studies and a Post Hoc Transcriptome Analysis of Involved Molecular Pathways.International journal of molecular sciences · 2022Review
- The potential mechanism of huazhuojiedu decoction in the treatment of ulcerative colitis based on network pharmacology and experimental validation.Frontiers in pharmacology · 2022Article
- Biological Activities Underlying the Therapeutic Effect of Quercetin on Inflammatory Bowel Disease.Mediators of inflammation · 2022Review
- St. John's Wort alleviates dextran sodium sulfate-induced colitis through pregnane X receptor-dependent NFκB antagonism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Flavonoids: structure-function and mechanisms of action and opportunities for drug development.Toxicological research · 2021Review
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- GB1a Ameliorates Ulcerative Colitis via Regulation of the NF-κB and Nrf2 Signaling Pathways in an Experimental Model.Frontiers in medicine · 2021Article
- Based on Network Pharmacology to Explore the Potential Bioactive Compounds and Mechanisms of Zuojin Pill for the Treatment of Ulcerative Colitis.Evidence-based complementary and alternative medicine : eCAM · 2021Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Isorhamnetin is an O-methylated flavonol present in fruit and vegetables. We recently reported the identification of isorhamnetin as an activator of the human pregnane X receptor (PXR), a known target for abrogating inflammation in inflammatory bowel disease (IBD). The current study investigated the role of isorhamnetin as a putative mouse PXR activator in ameliorating chemically induced IBD. Using two different models (ulcerative colitis like and Crohn's disease like) of experimental IBD in mice, we demonstrated that isorhamnetin abrogated inflammation through inhibiting the activity of myeloperoxidase, the levels of TNF-α and IL-6, the mRNA expression of proinflammatory mediators (iNOS, ICAM-1, COX2, TNF-α, IL-2 and IL-6) and the phosphorylation of IκBα and NF-κB p65. PXR gene overexpression inhibited NF-κB luciferase activity, and the inhibition was potentiated by isorhamnetin treatment. PXR knockdown by siRNA demonstrated the necessity for PXR in isorhamnetin-mediated up-regulation of xenobiotic metabolism genes. Ligand pocket-filling mutants (S247W/C284W and S247W/C284W/S208W) of human PXR weakened the effect of isorhamnetin on PXR activation. Molecular docking studies and time-resolved fluorescence resonance energy transfer competitive binding assays confirmed the ligand (isorhamnetin)-binding affinity. These results clearly demonstrated the ameliorating effect of isorhamnetin on experimental IBD via PXR-mediated up-regulation of xenobiotic metabolism and down-regulation of NF-κB signaling. The novel findings may contribute to the effective utilization of isorhamnetin or its derivatives as a PXR ligand in the treatment of human IBD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.