@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 {90, title = {Mass spectrometry methods to study protein-metabolite interactions.}, journal = {Expert Opin Drug Discov}, volume = {12}, year = {2017}, month = {2017 12}, pages = {1271-1280}, abstract = {

INTRODUCTION: To ​​​​understand and manipulate biochemical processes and signaling pathways, the knowledge of endogenous protein-metabolite interactions would be extremely helpful. Recent developments in precision mass spectrometry, high-throughput proteomics and sensitive metabolomic profiling are beginning to converge on a possible solution, heralding a new era of global metabolome-proteome {\textquoteright}interactome{\textquoteright} studies that promise to change biomedical research and drug discovery. Areas covered: Here, we review innovative mass spectrometry-based methods and recent pioneering studies aimed at elucidating the physical associations of small molecule ligands with cellular proteins. The technologies covered belong to two main categories: tag-based and tag-free methods. We emphasize the latter in this review, and outline promising experimental workflows and key data analysis considerations involved. Expert opinion: Recent ground-breaking advances in chemical-proteomics technology and allied computational methods now make the global detection of protein-ligand engagement an increasingly attractive research problem. Despite ongoing challenges, rapid progress in the field is expected these coming next few years, leading to a refreshed systems biology research paradigm and much needed new opportunities for improving sparse drug discovery pipelines.

}, keywords = {Biomedical Research, Drug Discovery, High-Throughput Screening Assays, Humans, Ligands, Mass Spectrometry, Metabolome, Metabolomics, Proteins, Proteome, Proteomics, Systems Biology}, issn = {1746-045X}, doi = {10.1080/17460441.2017.1378178}, author = {Guo, Hongbo and Peng, Hui and Emili, Andrew} } @article {99, title = {Peroxisome Proliferator-Activated Receptor γ is a Sensitive Target for Oil Sands Process-Affected Water: Effects on Adipogenesis and Identification of Ligands.}, journal = {Environ Sci Technol}, volume = {50}, year = {2016}, month = {2016 07 19}, pages = {7816-24}, abstract = {

Identification of toxic components of complex mixtures is a challenge. Here, oil sands process-affected water (OSPW) was used as a case study to identify those toxic components with a known protein target. Organic chemicals in OSPW exhibited dose-dependent activation of peroxisome proliferator-activated receptor γ (PPARγ) at concentrations less than those currently in the environment (0.025{\texttimes} equivalent of full-strength OSPW), by use of a luciferase reporter gene assay. Activation of PPARγ-mediated adipogenesis by OSPW was confirmed in 3T3L1 preadipocytes, as evidenced by accumulation of lipids and up-regulation of AP2, LPL, and PPARγ gene expression after exposure to polar fractions of OSPW. Unexpectedly, the nonpolar fractions of OSPW inhibited differentiation of preadipocytes via activation of the Wnt signaling pathway. Organic chemicals in OSPW that were ligands of PPARγ were identified by use of a pull-down system combined with untargeted chemical analysis (PUCA), with a recombinant PPARγ protein. Thirty ligands of PPARγ were identified by use of the PUCA assay. High resolution MS(1) and MS(2) spectra were combined to predict the formulas or structures of a subset of ligands, and polyoxygenated or heteroatomic chemicals, especially hydroxylated carboxylic/sulfonic acids, were the major ligands of PPARγ.

}, keywords = {Adipogenesis, Ligands, Oil and Gas Fields, PPAR gamma, Water}, issn = {1520-5851}, doi = {10.1021/acs.est.6b01890}, author = {Peng, Hui and Sun, Jianxian and Alharbi, Hattan A and Jones, Paul D and Giesy, John P and Wiseman, Steve} }