Erodium stephanianum-Derived Polyphenols Prevented the Progression of Collagen-Induced Arthritis in Mice and Its Associated Metabolic Alterations

Background: This study aimed to investigate the effects of E. stephanianum-derived polyphenols on preventing the progression of collagen-induced arthritis (CIA) in mice and its associated metabolic alterations. Methods: The E. stephanianum plant was extracted, fractionated, and screened in vitro for anti-inflammatory, antibacterial, and antioxidant potential. Fraction 5 (identified as ellagic acid by nuclear magnetic resonance) exhibited the most potent activity and was selected for in vivo study. In the in vivo study, male DBA/1JGpt mice were randomized into five groups: control (CON), CIA (Model), low-dose extract (ES-L), high-dose extract (ES-H), and ellagic acid group. ES-L, ES-H, and ellagic acid were administered by daily oral gavage at 375, 750, and 250 mg/kg body weight, respectively, for 8 weeks. Arthritis severity was evaluated based on paw thickness, clinical score, ankle joint histopathology, and serum proinflammatory cytokine levels. To reveal the associated metabolic alterations, serum metabolites were characterized by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Results: Both the whole extract and ellagic acid revealed pronounced anti-inflammatory, antibacterial, and antioxidant properties. In vivo treatment with ES-L, ES-H, or ellagic acid similarly and significantly ameliorated CIA severity, showing smaller paw swelling, reduced clinical arthritis scores, milder joint histopathological injury, and lower serum tumor necrosis factor-α and interleukin-6 concentrations than the model group. Untargeted metabolomics identified 20 differential metabolites, mainly including triacylglycerols (containing n-3 fatty acids), pro-inflammatory phospholipids, and spermic acid 1. Moreover, the treatments significantly altered amino acid and purine metabolism. Conclusions:E. stephanianum derived polyphenols, like ellagic acid, significantly prevented the progress of CIA in mice. These effects were associated with the alteration of metabolic profiles.