biostudies-literatureZhang Nthe Science and Technology Innovation Project of the China Academy of Chinese Medical Sciencesthe Independent Topic Selection Research Project of the Institute of Basic Theory of Chinese Medicine, China Academy of Chinese Medical Sciencesthe National Natural Science Foundation of China Youth ProgramScience and Technology Innovation Project, Chinese Academy of Traditional Chinese Medicine554https://www.ebi.ac.uk/biostudies/studies/S-EPMC12899346biostudies-literatureUnknown31(3)Rheumatoid arthritis involves chronic synovitis and immune-metabolic dysregulation, highlighting a need for multi-target therapies that jointly modulate metabolism and inflammation. We developed glycyrrhiza protein-paeoniflorin self-assembled nanoparticles (GP-PF NPs) and investigated their anti-arthritic mechanism in adjuvant-induced arthritis (AIA) mice, using UHPLC-Orbitrap-MS-based metabolomics. Male C57BL/6 mice (<i>n</i> = 42) were assigned to the control, model, GP-PF NPs, paeoniflorin, glycyrrhiza protein, physical mixture, and celecoxib groups. All groups except controls received complete Freund's adjuvant, and treatments were given intraperitoneally for 10 days. GP-PF NPs produced the greatest reduction in paw thickness versus the model (<i>p</i> < 0.0001) and outperformed all otMolecules (Basel, Switzerland)A UHPLC-Orbitrap-MS Metabolomics Strategy Reveals Glycerophospholipid Metabolic Remodeling Is Associated with the Anti-Arthritic Effect of Glycyrrhiza Protein-Paeoniflorin Nanoparticles via PI3K/AKT/NLRP3 Axis.PMC12899346(KYG-20240981403282YZX-202232CI2021A0O108Yang XBai DHuo MYang YLi CGao YZhang NfalseA UHPLC-Orbitrap-MS Metabolomics Strategy Reveals Glycerophospholipid Metabolic Remodeling Is Associated with the Anti-Arthritic Effect of Glycyrrhiza Protein-Paeoniflorin Nanoparticles via PI3K/AKT/NLRP3 Axis.Rheumatoid arthritis involves chronic synovitis and immune-metabolic dysregulation, highlighting a need for multi-target therapies that jointly modulate metabolism and inflammation. We developed glycyrrhiza protein-paeoniflorin self-assembled nanoparticles (GP-PF NPs) and investigated their anti-arthritic mechanism in adjuvant-induced arthritis (AIA) mice, using UHPLC-Orbitrap-MS-based metabolomics. Male C57BL/6 mice (<i>n</i> = 42) were assigned to the control, model, GP-PF NPs, paeoniflorin, glycyrrhiza protein, physical mixture, and celecoxib groups. All groups except controls received complete Freund's adjuvant, and treatments were given intraperitoneally for 10 days. GP-PF NPs produced the greatest reduction in paw thickness versus the model (<i>p</i> < 0.0001) and outperformed all ot2026-01-01T00:00:00Z2026 Feb2026-07-07T03:10:36.092Z2026-07-07T03:08:33.528ZS-EPMC128993464168353110.3390/molecules31030554