@article {287, title = {An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice.}, journal = {Nat Commun}, volume = {16}, year = {2025}, month = {2025 Feb 03}, pages = {1280}, abstract = {

The literature documenting the value of drug-like molecules found in natural products is vast. Although many dietary and herbal remedies have been found to be effective for treating intestinal inflammation, the identification of their active components has lagged behind. In this study, we find that a major ginger component, furanodienone (FDN), is a selective pregnane X receptor (PXR) ligand with agonistic transcriptional outcomes. We show that FDN binds within a sub-pocket of the PXR ligand binding domain (LBD), with subsequent alterations in LBD structure. Using male mice, we show that orally provided FDN has potent PXR-dependant anti-inflammatory outcomes that are colon-specific. Increased affinity and target gene activation in the presence of synergistically acting agonists indicates further opportunities for augmenting FDN activity, efficacy and safety. Collectively, these results support the translational potential of FDN as a therapeutic agent for the treatment and prevention of colonic diseases.

}, keywords = {Animals, Anti-Inflammatory Agents, Colitis, Colon, Furans, Humans, Inflammation, Ligands, Male, Mice, Mice, Inbred C57BL, Pregnane X Receptor, Zingiber officinale}, issn = {2041-1723}, doi = {10.1038/s41467-025-56624-0}, author = {Wang, Xiaojuan and Zhang, Guohui and Bian, Zhiwei and Chow, Vimanda and Grimaldi, Marina and Carivenc, Coralie and Sirounian, Savannah and Li, Hao and Sladekova, Lucia and Mott, Stefano and Luperi, Yulia and Gong, Yufeng and Costello, Cait and Li, Linhao and Jachimowicz, Matthew and Guo, Miao and Hu, Shian and Wilson, Derek and Balaguer, Patrick and Bourguet, William and Mani, Sridhar and Bonati, Laura and Peng, Hui and March, John and Wang, Hongbing and Wang, Shengpeng and Krause, Henry M and Liu, Jiabao} } @article {263, title = {Diindoles produced from commensal microbiota metabolites function as endogenous CAR/Nr1i3 ligands}, journal = {Nature Communications}, year = {2024}, author = {Liu, Jiabao and Malekoltojari, Aniaz and Asokakumar, Anjana and Chow, Vimanda and Li, Linhao and Li, Hao and Grimaldi, Marina and Dang, Nathanlown and Campbell, Jhenielle and Barrett, Holly and Sun, Jianxian and Navarre, William and Wilson, Derek and Wang, Hongbing and Mani, Sridhar and Balaguer, Patrick and Anakk, Sayeepriyadarshini and Peng, Hui* and Krause, Henry*} } @article {237, title = {Disclosing Environmental Ligands of L-FABP and PPARγ: Should We Re-evaluate the Chemical Safety of Hydrocarbon Surfactants?}, journal = {Environ Sci Technol}, year = {2023}, month = {2023 Aug 01}, abstract = {

Chemical contaminants can cause adverse effects by binding to the liver-fatty acid binding protein (L-FABP) and peroxisome proliferator-activated nuclear receptor γ (PPARγ), which are vital in lipid metabolism. However, the presence of numerous compounds in the environment has hindered the identification of their ligands, and thus only a small portion have been discovered to date. In this study, protein ffinity urification with ontargeted nalysis (APNA) was employed to identify the ligands of L-FABP and PPARγ in indoor dust and sewage sludge. A total of 83 nonredundant features were pulled-out by His-tagged L-FABP as putative ligands, among which 13 were assigned as fatty acids and hydrocarbon surfactants. In contrast, only six features were isolated when His-tagged PPARγ LBD was used as the protein bait. The binding of hydrocarbon surfactants to L-FABP and PPARγ was confirmed using both recombinant proteins and reporter cells. These hydrocarbon surfactants, along with \>50 homologues and isomers, were detected in dust and sludge at high concentrations. Fatty acids and hydrocarbon surfactants explained the majority of L-FABP (57.7 {\textpm} 32.9\%) and PPARγ (66.0 {\textpm} 27.1\%) activities in the sludge. This study revealed hydrocarbon surfactants as the predominant synthetic ligands of L-FABP and PPARγ, highlighting the importance of re-evaluating their chemical safety.

}, issn = {1520-5851}, doi = {10.1021/acs.est.3c02898}, author = {Gong, Yufeng and Yang, Diwen and Liu, Jiabao and Barrett, Holly and Sun, Jianxian and Peng, Hui} } @article {218, title = {Widespread formation of toxic nitrated-bisphenols indoors by heterogeneous reactions with HONO}, journal = {Science Advances}, year = {2022}, author = {Yang, Diwen and Liu, Qifan and Wang, Sizhi and Bozorg, Martin and Liu, Jiabao and Nair, Pranav and Balaguer, Patrick and Song, Datong and Krause, Henry and Ouazia, Boualem and Abbatt, Jonathan and Peng, Hui} } @article {130, title = {Toxicokinetics of Brominated Azo Dyes in the Early Life Stages of Zebrafish () Is Prone to Aromatic Substituent Changes.}, journal = {Environ Sci Technol}, volume = {54}, year = {2020}, month = {2020 04 07}, pages = {4421-4431}, abstract = {

Brominated azo dyes (BADs) have been identified as predominant indoor brominated pollutants in daycare dust; thus, their potential health risk to children is of concern. However, the toxicities of BADs remain elusive. In this study, the toxicokinetics of two predominant BADs, Disperse Blue 373 (DB373) and Disperse Violet 93 (DV93), and their suspect metabolite 2-bromo-4,6-dinitroaniline (BDNA) was investigated in embryos of zebrafish (). The bioconcentration factor of DV93 at 120 hpf is 6.2-fold lower than that of DB373. The nontarget analysis revealed distinct metabolism routes between DB373 and DV93 by reducing nitro groups to nitroso (DB373) or amine (DV93), despite their similar structures. NAD(P)H quinone oxidoreductase 1 (NQO1) and pyruvate dehydrogenase were predicted as the enzymes responsible for the reduction of DB373 and DV93 by correlating time courses of the metabolites and enzyme development. Further in vitro recombinant enzyme and in vivo inhibition results validated NQO1 as the enzyme specifically reducing DB373, but not DV93. Global proteome profiling revealed that the expression levels of proteins from the "apoptosis-induced DNA fragmentation" pathway were significantly upregulated by all three BADs, supporting the bioactivation of BADs to mutagenic aromatic amines. This study discovered the bioactivation of BADs via distinct eukaryotic enzymes, implying their potential health risks.

}, keywords = {Animals, Azo Compounds, Child, Dust, Embryo, Nonmammalian, Humans, Mutagens, Toxicokinetics, Zebrafish}, issn = {1520-5851}, doi = {10.1021/acs.est.9b07178}, author = {Han, Jiajun and Yang, Diwen and Hall, David Ross and Liu, Jiabao and Sun, Jianxian and Gu, Wen and Tang, Song and Alharbi, Hattan A and Jones, Paul D and Krause, Henry M and Peng, Hui} }